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Board Studying > Clinical > Flashcards

Clinical Flashcards

1
Q

Fragile X repeat cutoffs

A

normal <50,

Pre 56-200,

Path = 200 (methylated)

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2
Q

Fragile X premutation phenotypes

A

Female: Premature Ovarian Failure.

Males and females: Ataxia/Tremor

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3
Q

Coffin Lowry

A

X-linked - RPS6KA3

ID

Broad hands with tapered fingers

Frontal bossing, flat nasal bridge, downslanting PF, wide mouth

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4
Q

Transcription Coupled Repair disorder

A

Cockayne syndrome

Gene: CSA, CSB

Face: Sunken eyes RP, SNHL, ID, Intracranial calcifications, short stature, photosensitive

Think: similar to XP but no cancer + dysmorphci facies

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5
Q

Syndromes with nuchal translucency

A

>3.4mm cutoff

Turner, Down Syndrome, Noonan

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6
Q

Most common genes in non-syndromic HCM

A

MYBPC3, MYH7

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7
Q

Down syndrome dysmorphic features

A

Upslanting PF

Burshfield spots

Small ears

Short 5th digit

Sandlegap toes

epicanthal folds

Single palmar crease

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8
Q

Ddx: epicanthal folds

A

Asian descent

Down syndrome

Fetal Alcohol

Zellweger

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9
Q

Down Syndrome association

A

Endocardial cushion defect (AV canal)

Duodenal atresia

Hirschsprungs

Leukemia

Alzheimers

hypothyroidism

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10
Q

Marfan diagnostic criteria

A

GHENT criteria:

If no FHX:

root dilation + lens,

FBN1,

systemic score >7,

OR lens + FBN1

If positive FHX: lens, root, or systemic score

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11
Q

Homocystinuria vs Marfan

A

AR inheritance,

rigid joints,

strokes,

ID

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12
Q

Turner syndrome dysmorphic features:

A

Webbed neck

low hair line

low set ears

lymphedema

cubitus valgus

Madelung deformity

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13
Q

Noonan Dysmorphology

A

Downslanting PF

low set, posteriorly rotated ears with creases

Turner features (webbed neck, board chest, pectus, short, cubitus valgus)

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14
Q

Noonan associations

A

Pulmonic stenosis

HCM

Bleeding/clotting

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15
Q

Trisomy 18 dysmorphology

A

microcephaly with prominent occiput

rocker bottom feet

short sternum

thumb/radius agenesis/hypoplasia

clenched fist with overlapping fingers

horseshoe kidneys

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16
Q

Trisomy 13 dysmorphology

A

cutis aplasia

holoprosencephaly

midline cleft

polydactyly

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17
Q

Cutis aplasia associations

A

Trisomy 13

Adams Oliver

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18
Q

Fragile X dysmorphology

A

Long, triangular face

flattened nasal bridge

protruding ears

macro-orchidism

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19
Q

Treacher collins dysmorphology

A

Downslanting PF

eyelid coloboma

absent bottom eyelashes

microtia

conductive hearing loss

NORMAL intellect

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20
Q

22q11 Dysmorpohlogy

A

tubular nose with hypoplastic nares

long tapering fingers

Cleft

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21
Q

CDLS dysmorpology

A

hirsutism

Synophrys/arched eyebrows

down-turned corners of mouth

Limb reduction defects

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22
Q

Achondroplasia dyrmorphology/associations

A

Trident Hand

Macrocephaly

Frontal bossing

Mid face hypoplasia

Foramen magnum stenosis

OSA

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23
Q

Beckwith Wiedemann Dysmorphology

A

Macroglossia

umbilical hernia

ear pits/creases

hemihyperplasia

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24
Q

BW Syndrome Cancer risks

A

Wilms

hepatoblastoma

embryonal

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25
Q

Williams syndrome dysmorphology

A

Broad forehead

short nose with broad tip

full cheeks

wide mouth with full lips

Puffy full upper eyelid

blue eyes with stellate irides

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26
Q

Waardenburg dysmorphology

A

white forelock

iris heterochromia

cochlear deafness

dystopia canthorum (lateral displacement of inner canthi)

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27
Q

CAL spots

A

NF1 Mccune-albright

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28
Q

Lip pits

A

Van Der Woude syndrome

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29
Q

Freckled penis

A

PTEN - Bannayan-Riley-Ruvalcaba syndrome

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30
Q

Persistent Fetal pads and arched split eyebows

A

Kabuki (also ITP)

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31
Q

Deafness genes

A

GJB2 and 6

Connexin 26 and 30

GJB2 can be AR or AD

Also biallelic inheritance possible

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32
Q

Common GJB2 mutation

A

35 Del C

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33
Q

Deafness + Goiter

A

Pendred Syndrome, SLC25A4

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34
Q

Deafness + RP

A

Usher

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35
Q

Deafness + Conduction defect (long QT)

A

Jerveil and Lange Nielson syndrome

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36
Q

Management of carrier mothers for DMD

A

TTE for cardiomyopathy

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37
Q

Germline mosiacism risk for DMD

A

14%

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38
Q

DMD treatment

A

Steroids between 5 and 15yo, Exon Skipping: Antisense (Etiplirsen) skip Exon 51, ACEi/BBlocker,

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39
Q

Gardner

A

FAP +

CHRPE,

osteomas,

soft tissue tumor,

supernumery teeth

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40
Q

Turcot

A

FAP +

CNS (medulloblastoma)

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41
Q

FAP surveillance

A

Start at age 10-12 q2 years;

EGD start at 18-25

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42
Q

Attenuated FAP definition

A

<100 polyps, start colonoscopy at age 20 If APC gene negative, look at MYH

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43
Q

Familial Hypercholesterolemia diagnosis

A

Clin: Arcus, Xanthomas, xanthelasma, arthritis/tenosynovitis

Cholesterol: 300 (het), 600 (homo)

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44
Q

Treatment of familial hypercholesterolemia

A

Statin,

Bile acid sequestrant,

aphoresis,

nicotinic acid (niacin)

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45
Q

Phenocopy for familial hypercholesterolemia (LDLR)

A

Apo B,

PCSK9

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46
Q

Repeat for Fragile X, where is it located

A

CGG,

5’ UTR

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47
Q

Fragile X Stablizer

A

AGG repeats

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48
Q

Top 4 most common genetic causes of ID

A

Down,

22q11,

Williams,

Fragile X

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49
Q

Recurrence risk for ID is increased if proband is:

A

Male

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50
Q

X Linked causes of ID

A

XALD

MPSII

FRAX

Pelizaeus-Merzbacher

ATRX (Alpha Thal + ID)

Coffin Lowry

MECP2

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51
Q

Coffin Siris

A

Absent nail,

hypoplastic 5th digit

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52
Q

Simpson-Colabi-Behmel

A

Overgrowth

+ cardiac conduction defects

+ polydactyly

+ Wilm’s tumor, neuroblastoma

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53
Q

MECP2 duplication syndrome

A

Can affect males

  • severe ID, hypotonia, seizures, pseudo GI obstruction
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54
Q

Intracranial calcification syndromes

A

TORCH

Aicardi-Goutieres (TREX1; + encephalopathy, HSM, thrombocytopenia)

COL4A1 and COL4A2 - vascular basement membrane

Cockayne (CSA, CSB, ERCC; sunken eyes, retinopathy, SNHL)

Adams-Oliver (cutis aplasia)

Gorlin (PTCH1: BCC, teeth)

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55
Q

Most common causes of leigh syndrome

A

SURF1 (most common)

mtATP6 (T8993G/C)

PDH (X linked, common in males)

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56
Q

mt tRNAlys mutation causes

A

MERRF

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57
Q

Short rib, short limb, ectodermal dysplasia, polydactyly

A

Ellis Van Creveld, (EVC gene)

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58
Q

Most common Pulm HTN gene

A

BMPR2

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59
Q

Broad forehead, deep set eyes, triancular chin, pulm stenosis, cholestasis

A

Alagille syndrome

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60
Q

Sparse facial hair, hypertelorism, low set ears

A

CFC syndrome (BRAF, Rasopathy)

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61
Q

Heart defects associated with:

  1. Down syndrome
  2. 22q11
  3. Turner
  4. Williams
  5. Noonan/Costello/CFC
A
  1. AV canal
  2. TOF, interrupted AA, Truncus
  3. Outflow defects (Bicusp AV, Coarct, Root dilatation, dissection)
  4. Supravalvular AS
  5. Pulmonary stenosis, HCM, coagulopathy
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62
Q

First CHD gene

A

NKX2.5 - Tinman (has no heart in book)

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63
Q

5 syndromes with HCM

A

Fabry

Noonan

Friederich’s

Pompe

Danon

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64
Q

Most common causes of familial dilated cardiomyopathy

A

TTN (20%) LMNA (6%)

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65
Q

5 syndromes with dilated CM

A

DMD

Barth

LGMD

Emery dreifuss MD

Kearns-Sayre

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66
Q

AD Long QT genes

A

KCNQ1

KCNH2

SCN5A (events occur during sleep)

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67
Q

Jervell and Lange-Nielsen Syndrome

A

Long QT + SNHL

AR: KCNQ1, KCNE1

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68
Q

Brugada syndrome

A

Short QT

SNC5A + other Na, Ca, and K channels

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69
Q

Loeys-Diets vs Marfans

A

Craniofacial: Bifid Uvula, HyPERtelorism, craniosynostosis

Genes: TGFBR1, TGFBR2, SMAD3, TGFB2

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70
Q

COL5A1 and COL5A2

A

EDS type 1 and 2

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71
Q

COL3A1

A

EDS vascular

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72
Q

CHARGE heart defects

A

Dual outlet RV,

TOF

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73
Q

TBX5

A

Holt-Oram: AD

Cardiac (Conduction, ASD, VSD)

Limb defects

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74
Q

Alagille association

A

Peripheral pulmonary artery stenosis,

posterior embryotoxon,

butterfly vertebra

Triangular chin

Cholestasis

Jag1, Notch2: AD inheritance

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75
Q

What condition on quad screen does NIPS NOT cover

A

NT defect

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76
Q

When can CVS be performed

A

10-13 weeks (end of 1st trimester)

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77
Q

When can Amnio be performed

A

15-20 weeks

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78
Q

What factors determine effect of teratogen?

A

Fetal stage at exposure

Genotype of fetus

Dose/duration of exposure

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79
Q

When is all or nothing period of teratogen effect

A

0-2 weeks embryonic (2-4 wks) -> either death or nothing due to pluripotent cells

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80
Q

When is fetal period of greatest vulnerability

A

3-8 weeks embryonic (5-10 wks) -> organogenesis

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81
Q

Cat A drug

A

Controlled human studies show remote risk

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82
Q

Cat B drug

A

No controlled human studies, animal studies low risk

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83
Q

Cat C drug

A

Animal studies show risk, but may be acceptable

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84
Q

Cat D Drug

A

Risk in human studies, but may be necessary

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85
Q

Cat X Drug

A

Studies show major risk, do not give

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86
Q

Effects of radiation exposure in pregnancy

A

IUGR

microcephaly,

neuro

eye abnormalities

childhood leukemia

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87
Q

Effects of maternal hyperthermia

A

Exposure early (2-3 wks embryo age)

NTD

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88
Q

How do you convert embryo age into gestational age

A

Gestational age = embryo age + 2

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89
Q

Effects of maternal DM

A

11% risk (HgA1C >10) -> abnormal glycosolation

NTD,

cardiac,

renal/GI,

skeletal

Caudal regression/Sirenomelia

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90
Q

Maternal PKU

A

Mirocephaly,

ID,

cardiac

Keep Phe <360 u mol/L (6mg/dL)

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91
Q

Fetal mercury exposure

A

neurological and muscular injury

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92
Q

Fetal Polychorinated Biphenyls (cooking oil, some freshwater fish) exposure

A

DD, FTT, ectodermal dysplasia

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93
Q

Fetal lead exposure

A

Growth retardation, ID

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94
Q

TORCHES stands for:

A

Toxo

Other (Varicella, parvo B19, HIV)

Rubella

CMV

HErpes

Syphilis

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95
Q

Fetal B19 infection

A

Anemia,

thrombocytopenia

Tx: transfusion

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96
Q

Fetal Varicella

A

CNS and PNS

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97
Q

Fetal Rubella

A

Rash, hearing loss, liver

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98
Q

Features of fetal alcohol syndrome

A

Poor growth

DD

microcephaly

short palpebral fissures

short nose

smooth philtrum

thin upper lip

cardiac

small 5th fingernails

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99
Q

Fetal dilantin exposure (other AEDs similar)

A

Fetal Hydantoin syndrome (~10% of exposed)

(may have pharmacogenetic modifier -> dilantin epoxide)

Growth and mental delay

Wide fontanel

metopic ridging

hypertelorism

bowed upper lip

cleft l/p

hypoplastic distal phalanges/nails

hirsutism

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100
Q

Fetal VPA exposure

A

1% NTD

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101
Q

Fetal warfarin exposure 6-9 weeks

A

Nasal hypoplasia, depressed bridge

Stippling of epiphyses

Nail/fingertip hypoplasia

IUGR

ID

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102
Q

Fetal retinoic acid (accutane)

A

Ears: (microtia, anotia)

Mouth (micrognathia)

hypertelorism

conotruncal heart defects

CNS (hydrocephalus, microcephaly, DD)

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103
Q

Fetal thalidomide

A

Limb (amelia, finger/toe reduction)

CV

GI

NORMAL intellect

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104
Q

Fetal Tetracycline

A

Teeth/bone dyscoloration

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105
Q

Fetal SSRI

A

CHD (VSDs)

Neonatal irritability

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106
Q

Fetal AceI exposure

A

2nd Trimester -> Renal tubular dysgenesis

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107
Q

Fetal exposure to illicit drugs

A

Mostly not teratogens, but risk for IUGR, growth delay, vascular related placental issues

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108
Q

Presentations and inheritance pattern of G6PD

A

Kernicterus or hemolytic anemia X linked

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109
Q

What are the alleles for HFE

A

Cys282Tyr (higher risk)

His63Asp (only risk allele unless high risk allele also present)

Both incomplete penetrance

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110
Q

Most common mutation in Hemophilia A

A

Inversion in F8

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111
Q

Factor IX leiden

A

Variant Hemophilia B due to promoter mutation ->

severe in childhood, spontaneous improvement in adulthood

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112
Q

Major gene for isolated hirschsprung’s Which gender is more likely affected?

A

RET (AD, reduced penetrance)

Male > Females

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113
Q

4 most common genes in holoprosencephaly (AD)

A

SHH (35%)

ZIC2 (5%)

TGIF and SIX3 (1.5%)

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114
Q

HD repeat cutoffs

A

10-26 normal

27-35 premutation

36-39 incomplete penetrance

40-59 HD

60+ Juvenile HD

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115
Q

Which HD allele is more likely to expand?

A

Paternal

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116
Q

Where is the HD repeat expansion?

A

CAG in exon 1

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117
Q

Open fontanelle + exorbitism

A

Cruzon

FGFR2

+? SNHL, teeth abnormalities, frontal bossing, midface hypoplasia

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118
Q

Open fontanelle + small clavicles

A

Cleidocranial dysostosis

RUNX2

+ delayed/hypoplastic teeth, short stature, brachydactyly

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119
Q

Open fontanelle + stippled epiphysis

A

Zellweger

Check VLCFA

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120
Q

First test when differences in isomerism/laterality is found in baby

A

TTE - many CHD associated; heart loop is first morphological sign of assymetry in embryogenesis

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121
Q

Leukodystrophy with macrocephaly

A

Canavan (ASPA)

Alexander (GFAP)

Tay Sachs (HEX A)

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122
Q

Leukodystrophy + peripheral neuropathy

A

Metachromatic (ARSA) -posterior predominant

Krabbe (GALC)

Mitochondrial - DARS 2 w/ spinal cord involvement

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123
Q

Prodominantly anterior leurkodystrophy with macrocephaly

A

Alexander Disease (GFAP)

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124
Q

Leukodystrophy + intracranial calcifications

A

Aicardi-Goutieres

TREX1, RNASEH2A/2B/2C

CNS + fever, thrombocytopenia, HSM, anemia

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125
Q

Hypomyelination, sunken eyes, photosensitivity

A

Cockaye

ERCC1 and ERCC2

Also retinopathy, deafness, calcifications

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126
Q

X linked hypomyelinating disorder

A

Pelizaeur Merzbacher

PLP1

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127
Q

Teratogens that cause limb reduction defects

A

Thalidomide (+ CHD, phenocopy TBX5)

VPA

Phenytoin

Warfarin

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128
Q

Cutis aplasia + Limb reduction

A

Adams Oliver

AD: ARHGAP31 (rho GTPase), RBPG, Notch1, DLL4

AR: EOGT, DOCK6

Also neuro, cardiac, ophtho (retinal vascular disease)

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129
Q

Radial Ray + Heart defects

A

Hold Oram

TBX5

Thalidomide can look the same

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130
Q

Common Non-genetic causes of limb reduction

A

Amniotic band

VACTERL

Moebius syndrome (CN affected)

Poland (absent sternal head of pectoralis major)

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131
Q

Limb reduction + IUGR + synophyrys

A

CDLS

NIPBL, SMC1, SMCA, SMC3

+ hirsutism, anteverted nares, long smooth philtrum, micrognathia, cardiac defects, CNS

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132
Q

3 common genes for isolated and syndromic lisencephaly

A

PAFAH1B1

TUBA1A,

DCX (males, dual cortex in females)

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133
Q

Lisencephaly + hypertelorism, long/broad/think upper lip

A

Miller Dieker

PAFAH1B1 (17p13 deletion)

Dysmorphic: tall forehead, bitermporal narrowing, hyperteloric, short nose, iverted vermilion with prominent upper lip

CHD, omphalocele, contracture

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134
Q

Multiple brain malformations - lisencephaly, thin CC, BG abnormalities, polymicogyria

A

Tubulinopaties

TUB1A1, TUBB2A, etc

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135
Q

Cobbleston lisencephaly, retinal problems, hypotonia

A

Congenital musclular dystrophies

Muscle eye brain/walker warburg/fukayama

O-linked glycosylation disorders

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136
Q

macrocephaly + polymicrogyria

A

PIK3CA

mosiac

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137
Q

Lipoma + overgrowth of limbs

A

Proteus syndrome

AKT1

Mosiac

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138
Q

Skin Ca + GI/GU cancer

A

Muire Torre

MSH2, MSH1 (Lynch genes)

DDx: gardners

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139
Q

Cone shaped epiphysis + subcutaneous calcified nodules + hand abnormalities

A

Albright hereditary osteodystrophy

GNAS

+ short 4th/5th metacarpels, short distal phalanges of thumb,

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140
Q

Most common cause of 46XX, ambiguous genetalia

A

CAH

21 hydroxylase deficiency

NBS: high 17-OHP

Evaluate for salt wasting

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141
Q

Penile freckling + macrocephaly

A

Cowden/Bannayan-Riley-Ruvalcaba Syndrome

PTEN

Hamartoma syndrome - vascular, lipoma, breast, thyroid, endometrial, GI

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142
Q

2/3 toe syndactyly

A

SLOS

DHCR7

BIochem: measure 7 dehydrocholestrol level

FTT, microcephaly, ID, cleft palate, CHD, ambiguous genetalia

Monitor: AST/ALT, cholesterol

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143
Q

Femur/tibia bowing, 46 XY sex reversal

A

Campomelic dysplasia

SOX 9 (autosomal SRY activator)

Cleft palate, CHD

monitor: Gonadoblastoma

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144
Q

Wilms tumor, aniridia, ambiguous genetalia, ID

A

WAGR

11p13 del (WT1 and PAX6)

Also look for ESRD

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145
Q

Wilms tumor, ambiguous genetalia, renal failure

A

Denys-Drash

WT1 gene

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146
Q

Ambiguous genetalia, renal failure, gonadoblastoma

A

Frasier syndrome

WT1

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147
Q

CHD, radial ray defect, anal anomalies

A

VACTERL

Unknown, ZIC3 (X linked)

Vertebral

Anal

Cardiac

TEF

esophageal atresia

Renal

Limb

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148
Q

imperforate anus, triphalangeal/hypoplastic thumb

A

Towns Brock

SALL1 (zinc finger)

+ ear tags, SNHL

  • ESRD, CHD
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149
Q

Imperforate anus, polydactyly, hypothalamic hamartoblastoma, hypopituitary

A

Pallister Hall

GLI3

  • Bifid epiglottis

Manage endo issures

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150
Q

PAX6

A

aniridia

Ch 11p13

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151
Q

Contractures/arthrogryposis, marfanoid habitus, crumpled ears

A

Congenital Contractural Arachnodactyly (beals)

FBN2

  • Watch for kyphoscoliosis

heart defects (interrupted aortic arch, root dilation)

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152
Q

SCA + Parkinsonism

A

SCA3

Portugese

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153
Q

SCA + RP

A

SCA7

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154
Q

SCA + Oculomotor apraxia

A

SCA2

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155
Q

Which SCAs are repeat expansions?

A

CAG repeats

SCA1, 2, 3, 6, 7

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156
Q

Ataxia + neuropathy + Cardiomyopathy

A

Friedreich’s ataxia

Frataxin (FRDA)

GAA intronic repeat

Normal : 6-34

Disease: 67-1700

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157
Q

Ataxia + low Vit E

A

TTPA

Alpha-tocopherol transfer protein

Treatable

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158
Q

brachydactyly with shawl scrotum

A

Aarskog

FGD1

+ short stature (rhizomelia)

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159
Q

Broad thumbs with bifid nails/distal phalanges, duplicated hallux with syndactyly of 1-3 toes, macrocephaly, high forehead

A

Greig cephalopholysyndactyly

GLI3

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160
Q

Coronal craniosynostosis, broad thumb

A

Pfeiffer syndrome

FGFR1 or FGFR2 (more severe)

  • May have cloverleaf skull
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161
Q

Broad thumb and hallux, beaked nose, with columella below ala nasae

A

Rubinstein Taybi

CRBBP, EP300

Cryptorchidism, CHD, FTT, ID

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162
Q

Cardiomyopathy, wrinkled palms, ulnar dev of hands, coarse face

A

Costello syndrome

HRAS

Monitor for pelvic rhabdomyosarcoma

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163
Q

Myopathy, cardiomyopathy, neutropenia

A

Barth syndrome

X linked

Taffazin

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164
Q

Cerebellar hypoplasia, deep posterior interpeduncular fossa (molar tooth)

A

Joubert

Ciliopathy

Dysmorphic - low set ears, high eyebroas, triangular shaped mouth

Renal cystic disease

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165
Q

Elevated 8-dehyrocholesterol and 8,9 cholestenol

A

XL-RCDP in females (Male lethal)

EPB gene

+ assymetric limb involvement

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166
Q

RCDP + hypoplasia of distal phalanges

A

XL RCDP - males

ARSE

  • Can also be seen in pseudo-warfarin embryopathy (vit K eposide reductase)
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167
Q

RCDP with assymetric limb involvement

A

XL RCDP (females, male lethal)

high 8 dehydrocholesterol and 8,9 cholestanol

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168
Q

RCDP + nasal hypoplasia

A

Warfarin embryopathy

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169
Q

Cleft lip/palate laterality

A

L>R

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170
Q

Midline clefting DDX

A

Oralfacialdigital syndrome

Ellis Van Creveld (short rib, polydactyly, CHD)

holoprosencephaly

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171
Q

Cleft L/P + lip pits

A

Van Der Woude

IRF6 (interferon regulating factor) AD

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172
Q

Cleft l/p + myopia, deafness, hypermobility, arthritis

A

Stickler

COL2 and COL9, AD

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173
Q

Croase facies, short/obese, small hands/feet

A

Smith Magenis

RAI1

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174
Q

isochromosome 12p

A

Pallister Killian

Moasic (47+12p)

Need skin biopsy

Coarse face, hypertelorism, ID

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175
Q

Overgrowth syndrome + polydactyly, supernumery nipples

A

Simpson-Colabi-Behmel

Glypican 3 (X linked)

-Wilms tumor risk

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176
Q

Hypoplasia of distal 5th digit, DD, sparse scalp hair

A

Coffin Siris

SMARCA4, ARID1A, ARID1B

Coarse face

Bushy eyebrows

Cardiac, GU anomalies

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177
Q

22q11 marker -> tetrasomy 22q11

A

Cat eye syndrome

Anal, ear pits/tags, CHD, coloboma, renal, ID

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178
Q

4p16 deletion

A

Wolf Hirschorn

FTT, ID, greek-helmet face (short nose/philrum, high forehead, hypertelorism), coloboma

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179
Q

Coloboma of lower eyelid, micrognathia, malar hypoplasia, downlanding PF

A

Treacher Collins

TCOF1, POLR1D

Also ear abnormalities (microtia), cleft l/p, Pierre Robain sequence

Normal intellect

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180
Q

Peripheral Pulm artery stenosis, Posterior embryotoxon, butterfly vertebra

A

Alagille

JAG1, Notch2

hypoplasia of bile ducts -> jaundice

also TOF

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181
Q

Branchial cleft, hearing loss

A

Branchio-oto-renal syndrome

EYA1 (AD)

Also reonal dysplasia/agenesis

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182
Q

Hearing loss + RP

A

Usher syndrome

MYO7A

RP usually symptomatic in teens

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183
Q

Low set, prominent, posteriorly rotated ears with deficiency cartilage and hypoplastic lobes. “Cup shaped”

A

CHARGE

CHD7

Coloboma, heart, atresia choanae, growth retardation, genetal, ear anomaly

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184
Q

ear pit + imperforate anus

A

Towns brock

SALL1 (AD)

+ triphalangeal or hypoplastic thumb

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185
Q

FTT + dry/lax skin

A

RASopathy

CFC (pulm stenosis)

Costello (wrinkled hands, HRAS)

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186
Q

Assymetric growth restriction, triangular face, relative macrocephaly

A

Russel Silver

Hypomethylaton of 11p Imprinting control region (ICR1)

Maternal UPD7

May have hypoglycemia, GU anomalies

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187
Q

Wormian bones (extra bones between sutures)

A

Type I OI

COL1 deletions (other variants cause more severe phenotype - type II OI - due to dominant negative effect)

Blue sclera

Tx with bisphosphonates

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188
Q

Most common albinism in caucasians

A

OCA1

TYR (tyrosinase)

White hair at birth

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189
Q

Most common albinism in Africans

A

OCA 2

P gene

Some pigment at birth, gets lost with age

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190
Q

Albinism + syndromes

A

PKU (PH, low tyr)

Homocystinuria (CBS)

Prader Willi (P gene is by ch 15)

Menkes (ATP7A, copper metab, kinky hair)

Cheidack Higashi (LYST, giant melanosomes, + infection/neuro/bleeding)

Hermansky Pudluck (HPS, pale, bleeding, Puerto Rican + pulmonary fibrosis)

Cystinosis (CTNS)

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191
Q

Hemihypertrophy + epidermal nevi

A

Proteus syndrome

AKT1

  • vascular malformations, lipomas, lymphatic malformations
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192
Q

Wilms tumor surveillance

A

US every 3-4 monhts until age 8

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193
Q

holoprosencephaly + polydacytly + hypothyroidism

A

Pallister hall

GLI3, AD

Hypothalamic hamartoma, hypothyroidism

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194
Q

aqueductal stenosis, CAL spots

A

NF1

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195
Q

Beighton scoring and cutoffs for abnormal

A

9 total

2 each for pinky, thumb, elbow, and knees

1 point for touching floor w/ palms

Abnormal cutoffs:

>6 pre puberty

>5 post puberty

>4 over 50

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196
Q

hypermobile + high arched palate w/ dental crowding

A

Marfan

FBN1

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197
Q

hypertrichosis + nail hypoplasia

A

Coffin-Siris

ARID1B

Coards, sparse hair, nail hypoplasia (5th digit)

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198
Q

Hypertrichosis cubiti

A

Wiedemann Steiner

KMT2A (AD)

ID, excess hair at elbow, back, legs

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199
Q

hypertrichosis + broad thumbs

A

Rubinstein taybi

CREBBP, EP300

postnatal short stature, microcephaly, broad thumbs/halluces

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200
Q

hypoglycemia, macrocephaly, jaundice

A

SOTOS

NSD1 (AD)

ID, hyptotonia

Dysmorphic: Long narrow face w/ long chin

Overgrowth

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201
Q

What does G6PD do?

A

First enzyme of hexose monophosphate shunt - generate nicotinamide edenine dinucleotide phosphate (NADPH) -> glutathione regeneration

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202
Q

Heinz bodies in erythrocytes

A

G6PD defciency

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203
Q

Limb reduction + thrombocytopenia

A

Thrombocytopenia-absent radius syndrome

RBM8A

  • thumbs are present
  • may have renal and cardia cfindings
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204
Q

Limb defect + hypohydrosis + sparse hair + hypodontia

A

Ectrodactyly-Ectodermal dysplacia -Clefting (EEC)

TP63 (AD)

-Absent eyelashes/eyebrows

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205
Q

Cardiac myxoma, cutaneous myxoma, schwannomas

A

Carney complex

CNC1 (AD)

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206
Q

Dolichocephaly, prominent forehad, long/narrow face, long chin + DD + overgrowth

A

Sotos syndrome

NSD1 (AD)

Monitoring: Cardaic, renal, scoliosis, hearing loss

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207
Q

microcephaly, cleft palate, syndactyly

A

SLOS

7 dehydrocholesterol reductace (DHCR)

2/3 toe syndactyly, ambigous genetalia, DD

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208
Q

microcephaly + broad thumbs and halluces

A

Rubenstein Taybi

CREBBP, EP300

Postnatal growth restriction, ID

Downslanting PF, beaked nose

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209
Q

Micrognathia, cleft palate, upper airway obstruction

A

Pierre - Robin sequence

2/3 isolated

1/3 complex (22q, stickler, etc)

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210
Q

Robin sequence + myopia, deafness

A

Sticker

COL2, COL9, COL11

-myopia, deafness, arthropathy

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211
Q

Robin sequence + CHD

A

22q11

  • look for hypocalcemia, immunodeficiency

CHD: arch abnormalitites - IAA or truncus

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212
Q

Micrognathia + inferior eyelid coloboma

A

Treacher Collins

TCOF, POLR

+ microtia, malar hypoplasia, SNHL

  • Intellect normal
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213
Q

anophthalmia + polydactyly + cleft

A

Trisomy 13

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214
Q

What assessment should be performed in patients with bilateral ear pits?

A

Hearing assessment

Renal US if dysmorphic

  • Treacher collins, Brachio-oto-renal
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215
Q

What should you think about when seeing inverted nipples?

A

CDG

Propionic acidemia

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216
Q

Flat nasal bridge + myopia, vitreous gel anomaly, cleft palate, deafness

A

Stickler Syndrome

COL2, 9, 11

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217
Q

nasal hypoplasia + RCDP

A

Warfarin

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218
Q

high nasal root, short nose, short phildrum, DD, FTT, hypotonia

A

Wolf Hirschhorn

4p delesion

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219
Q

Beaked nose (columella below alae nasi), broad thumb, downslanting PF

A

Rubenstein Taybi

CREBBP, EP300

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220
Q

hooked nose, exorbitism

A

Crouzon syndrome

FGFR2

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221
Q

neonatal encephalopathy, alopecia, rash, hypotonia

A

Biotinidase deficiency

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222
Q

EIEE + apnea + burst suppression

A

NKH

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223
Q

EIEE + lens dyslocation

A

Sulfite oxidase deficiency or Molybdenum Cofactor Deficiency

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224
Q

Alexander disease genetics

A

GFAP

AD (de novo)

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225
Q

Microcephaly, hirschsprung, hypospadias

A

Mowat Wilson

ZEB2

-Also ear anomalies, agenesis of CC

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226
Q

Bilaterally posterior ear pits, and creases

A

Beckwith Weidemann

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227
Q

FHx: Triple neg breast ca, ovarian cancer, melanoma, endometrial ca, prostate ca

A

BRCA1/2

Higher risk of breast and ovarian cancer in BRCA1

Higher risk of male breast ca in BRCA2 (8% vs 2%)

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228
Q

What % of pancreatic and ovarian ca can be attributed to BRCA1/2?

A

10% epithelial ovarian Ca and 5% of pancreatic

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229
Q

What are the NCCN high penetrance Breast and Ovarian ca genes

A

BRCA1, BRCA2, (breast, ovarian)

CDH1, (Diffuse gastric cancer + lobular breast ca)

PALB2, (allelic with fanconi, breast and ovarian ca)

PTEN (Cowden - GI hamartoma + macrocephaly + endometrial/breast/thyroid)

TP53 (Li frameni - soft tissue sarcomas, less ovarian)

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230
Q

NCCN High risk breast/ovarian Cancer screening

A

age 25: clinical exam every 6-12 months

25-29 - annual MRI (exposure to radiation before age 30 associated with increased risk of ca)

30-75- annuam mammo or MRI

  • Discuss mastectomy
  • SP Oophorectomy after childbearing ~ 35-40
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231
Q

Macrocephaly, GI hamartomas, Endometrial/breast/thyroid cancer

A

PTEN

Cowden Syndrome

Can also have neurodevelopmental phenotype in childhood

+ lipomas, colon ca, RCC, mucoutaneous skin lesions

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232
Q

Should TP53 patients get Bilateral salphingo-oophorectomy?

A

Li Frameni

  • Multiple soft tissue sarcomas (including breast ca)

BSO NOT recommended prophylactically, low risk of ovarian cancer

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233
Q

GYN cancer syndromes

A

BRCA1, BRCA1

Lynch

Peutz Jegher (STK11)

Gorlin

DICER1

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234
Q

Colon Ca + ovarian Ca + endometrial ca + gastric Cancer

A

Lynch syndrome

MLH1, MSH2, MSH6, PMS2

Endometrial up to 60%, Ovarian 25%

  • Also intestine, CNS, urothelial, pancreatic, and prostate

Tx: Gene specific recommendations:

  • TAH-BSO in MLH1 and MSH6

Colonoscopy starting at 20 -25

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235
Q

Ovarian fibroma + BCC + jaw cysts + medulloblastoma

A

Gorlin

PTCH1

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236
Q

Hypotonia and FTT in infancy -> truncal obesity and small hands/feet

ID, hypogonadotropic hypogonadiam

A

Prader Willi

15q11 (pat genes)

Causes: 75% pat deletion, 25% maternal UPD, 1% imprinting defect

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237
Q

Obesity, DD, retinopathy, nephropathy

A

Barbed Beidl

BBS

Ciliopathy

+ preaxial polydactyly

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238
Q

Obesity, short stature, shortening of distal phalanges and metacarpals, coned epiphysis, ID, subcutaneous nodules

A

Albright hereditary osteodystrophy

Inactivating GNAS mutations AD

Tissue specific imprinting:

Maternal mutations -> pseudohypoparathyroidism (resistance to PTH -> PTH high)

Paternal; -> Pseudopseudohypoparathyroidism (labs are normal)

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239
Q

Obese, short stature, small hands/feet

Sleep disturbance, self hugging, self harm

A

Smith Magenis syndrome

17p11 deletion: RAI1

  • Prader Wili like + prominent sleep/behavioral phenotype
  • Check for this whenever PWS is negative
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240
Q

Hypertelorism, macrocephaly, high forehead, bifid thumbs and toes

A

Greig cephalopolysyndactyly

GLI3

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241
Q

Hypertelorism, rhizomelia, hyperextendable PIP joints, shawl scrotum

A

Aarskog,

FGD1 (XL)

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242
Q

Syndromic causes of edema infancy

A

Noonan, Turner, GM1 gangliosidosis

Variable: Proteus (AKT1)

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243
Q

TEF + radial limb defect

A

VACTERL

(Small percentage due to ZIC3, Kynureniase deficiency - tryptophan metabolism)

Vertebral

Anal atresia

Cardaic

TracheoEsophageal Fisula

Renal

Limb

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244
Q

TEF + dysplastic external ear, Coloboma

A

CHARGE (CHD7)

Coloboma

Heart

Atresia of chloanae

Regardation (growth and intellect)

Genital

Ear anomalies

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245
Q

What condition do you need to exclude in babies with duodenal atresia

A

Down syndrome

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246
Q

Overgrowth + dolicocephaly, ID, fronto-temporal hair sparsity, hypotonia

A

Sotos syndrome

NSD1 (AD)

  • Also cardiac, renal anomalies and seizures
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247
Q

Overgrowth, macrocephaly, hemangiomas, follicular thyroid tumor, breast ca, lipoma

A

PTEN hamartoma syndrome

Bannayan-Riley-Ruvalcaba - childhood w/ penile freckling

Cowden - adult form -> multiple hamartomas

248
Q

Overgrowth + syndactyly, midline groove in lower lip

A

Simpson-Golabi-Behmel

GPC3 (XL)

Overgrowth

Dysmoprhic

Hand anomalies

Congenital anomlaies: Heart, renal, Congenital diaphragmatic hernia

Tx: Surveillane for embryonal and wilms tumor

249
Q

Overgrowth, abd wall defects, ear creases/posterior pits

A

Beckwith-Wiedemann

11p15 epigenetics

monitor for wilms tumor

250
Q

Regional overgrowth syndromes

A

Mosiac disorders:

PIK3CA (brain malformations, hemimegaencephaly)

Proteus - ATK1 - cerebriform naevi, linear epidermal naevi, vascular/lymphatic malformations

251
Q

Duodenal atresia, diaphragmatic hernia, corneal clouding, nail hypoplasia

A

Fryns syndrome

unknown gene

252
Q

Jejuno-Ileal atresia

A

Cystic Fibrosis

CFTR

253
Q

hypopigmented macule + ependymoma + epilepsy

A

TSC

Hypopigmented macule = ash leaf spot

Raised leathery patch = Shagreen’s patch

254
Q

Skin hypopigmentation + white forelock + heterochromia

A

Waardenburg

Pax3

+ Deafness, synophorys, dystopia canthorum

255
Q

Blistering lesions along lines of blaschko (first few days) ->

LE verrucous lesion (<6 months) ->

axillary/groin hyperpigmentation (>6 months) ->

pale atrophic streaks (childhood)

A

Incontentia pigmenti

IKBKG (XL, male lethal)

+ alopedia, dental problems

  • Free melanin granules if hyperpigmented streak is biopsied

Tx: Retina exam, cosmetic dentistry

256
Q

What are typical CAL macule findings in NF1 vs NF2

A

NF1 - 6 or more (5mm pre puberty, 15mm post puberty)

NF2 - <6

257
Q

craniosynostosis + broad thumbs/halluces

A

Pfeiffer syndrome

FGFR1 (5%)

FGFR2 (95%)

258
Q

Craniosynostosis + Cleft Palate + syndacytly

A

Apert syndrome

FGFR2

Ser252Try or Pro253Arg

259
Q

Postaxial polydactyly + Retinal dystrophy + Obesity + renal dysfunciton

A

Bardet Biedl

BBS genes

Ciliopathy

260
Q

Broad, duplicated thumbs, polydactyly, macrocephaly, hypertelorism

A

Greig Cephalopolysyndactyly

GLI3 (AD)

261
Q

Mesoaxial polydactyly, imperforate anus, hypopituitarism, hypothalamic hamartoblastoma

A

Pallister-Hall (anocerebrodigital syndrome)

GLI3 (AD)

  • bifid epiglottis
262
Q

Triphalangeal Thumbs, absent thumbs, CHD

A

Holt Oram

TBX5 (AD)

  • Upper limbs only
263
Q

Triphalangeal thumbs, hypoplastic thumb, imperforate anus, dysplastic ears, SNHL

A

Towns brock

SALL1

+ CHD

264
Q

UGT1A1 homozygosity for A(TA)7TAA promotor insertion

A

Gilbert syndrome

Most common cause of mild unconjugated hyperbilirubinemia

~50% of north american’s are carriers, 9% homozygous

265
Q

UGT1A1 LOF mutations

A

Crigler Najjar syndrome

  • Non-hemolytic unconjugated hyperbilirubinemia

Tx: Phototherapy

266
Q

Neonatal jaundice, prominent/pointed chin, deep set eyes, straight nose w/ bulbous tip,

A

Alagille syndrome

JAG1, NOTCH2

Slit lamp exam -> posterior embryotoxon

Peripheral pulmonary artery stenosis

Face: Prominent forehead, deep set eyes, hypertelorism, pointed chin, saddle/straight nose w/ bulbous tip

267
Q

Jaundice, large fontanelle, hypotonia

A

Zellweger Spectrum

PEX genes

VLCFA up, Plasmalogen low, Phytanic high

268
Q

Neonatal jaundice, hepatmegaly, neurodegeneration, cherry red macula

A

Niemann Pick A

Acid Sphingomyelinase (SMPD1)

NPB presents later

269
Q

Jaundice, overgrowth, dolichocephaly, pointed chin

A

Sotos Syndrome

NSD1 (AD)

  • Look for microdeletion 5p35 in japanese patient
270
Q

Assymetric coronal suture craniosynostosis, low frontal hairline, ptosis, proximally inserted thumb, small ears w/ prominent crus

A

Saethre-Chotzen

TWIST1

  • look for skin syndactyly, broad halluces
271
Q

What do you need to look for in patients with blepharophimosis, ptosis, and epicanthus inversus syndrome?

A

Premature ovarian failure

272
Q

Overgrowth + CHD + polydactyly

A

Simpson Golabi Behmel

GPC3, GCP4

273
Q

Neonatal jaundice + adult COPD

A

Alpha 1 antitrypsin

SERPINA1

274
Q

Rhizomelia, ptosis, hypertelorism, hyperextendable PIP, shawl scrotum

A

Aarskog

FGD1

275
Q

Bilateral thumb anomalies, CAL spots, microcephaly

A

Fanconi amenia

  • Chromosomal breakage analysis
276
Q

Radial ray anomalies, growth retardation, anemia

A

Diamond Blackfan Anemia

RPS and RPL genes

Tx: transfusion, HSCT

277
Q

Radial ray defect, tracheal esophageal fistula, renal agenesis, anal agresia

A

VACTERL

Vertebral

Anal

Cardiac

TEF

Renal

Limb

278
Q

Autosomal dominant radial ray defect + CHD

A

Holt Oram

TBX5

  • Always bilateral, can be any upper limb anomly

+ CHD

DDx: thalidomide

279
Q

Retinal dystrophy + hydrocephalus + neuronal migration defects

A

Congenital Muscular dytrophy (Walker warburg, muscle - eye-brain)

POMT (O linked CDGs)

280
Q

RP + deafness

A

Usher (+ balance issues)

Refsum disease (+ high phytanic acid, neuropathy, skeletal changes)

Cockayne (+photosensitivity, growth failure, intracranial calcifications)

281
Q

RP + obesity + renal dysfunction

A

Bardet Biedl

Ciliopathy, BBS genes

282
Q

High ornithine, night blindness, myopia

A

Gyrate atrophy

OAT (ornithine aminotransferase)

283
Q

RP + seizures + neurodegneration

A

Neuronal Ceroid Lipofucsinosis

CLCN 1, 2, 3

Enzymes: Palmitoyl-Protein thioesterase (PPT), Tripeptidyl-peptidase (TPP)

284
Q

Transverse limb defect + scalp defect

A

Adams Oliver

ARHGAP31, DLL4, NOTCH1, RBPJ (AD)

DOCK6,EOGT (AR)

  • may have developmental delay or pulmonary HTN
285
Q

What gene accounts for short stature in Turner Syndrome?

A

SHOX haploinsufficiency

286
Q

Short stature, triangular face w/ assymetry, disproportionately large head

A

Silver-Russell syndrome

60% hypomethylation of ICR1 on chromosome 11p15

10% maternal UPD7

287
Q

Short stature, rhizomelia, hypertelorism, brachydactyly with hyperextensible PIP joines

A

Aarskog

FGD1 (XL)

+ Shawl scrotum

288
Q

Short stature, obesity, short 4th/5th metacarpals, subcutaneous nodules

A

Albright hereditary Osteodystrophy

GNAS LOF

289
Q

Postnatal short stature and microcephaly, ID, broad thumbs, pilomatrixoma

A

Rubinstein Taybi

CREBBP, EP300 - abnormal histone acetylation

+ beaked nose, cryoporchidism, CHD, sleep apnea

Tumors: Meningioma, pilomatrixoma, leukemia

290
Q

short stature, microcephaly, hirsutism, limb reduction, ID, diaphragmatic hernia

A

CDLS

NIPBL (AD), SMC1A, SMC3, HDAC8, RAD21

+ synophorys, pulmonary valve stenosis

291
Q

agenesis of the corpus callosum, hypertelorism, pointed chin, prominent columella, broad medial flared eyebrows, uplifted earlobes, hypospadias

A

Mowat Wilson

ZEB2

+ CHD

292
Q

craniosynostosis with syndactyly

A

Apert syndrome

FGFR2

+ ID

293
Q

Absent sweating, dry skin, sparse hair, peg shaped teeth

A

Hypohydrotic ectodermal dysplasia

EDA (XL) - also AR and AD forms

Death due to hyperpyrexia during infections

294
Q

What are the non-skin findings in Incontinentia pigmenti?

A

NEMO (XL)

skin: blistering -> verrucous -> Hyper -> Hypopigmented

Non skin: Nail dystrophy, dental anomalies, patchy alopecia, seizures all ectodermal stuff

295
Q

Sparse hair, nail hypoplasia (5th digit), coase facies

A

Coffin Siris

ARID1B - chromatin remodeling - AD de novo

296
Q

Wormian bones, sparse steely hair, pili torti, neurodegeneration

A

Menke’s disease

ATP7A (XL) -> copper metabolism

297
Q

FGFR3 c.1138G>C, p.G380R

A

Achondroplasia

rhizomelic short stature

trident hard (wedge shaped gap between 3rd and 4th digit)

  • OSA, cervical instability, hydrocephalus
298
Q

FGFR3 c.1620C>A, p. N540K

A

Hypochondroplasia

milder achondroplasia, X rays may be normal until age 2

299
Q

What is the pathophysiology of achondroplasia?

A

GOF -> constitute activation of normally inhibitory function of FGFR3

300
Q

What disease and how much enzyme activity do homogyzotes with GLu342Lys in SERPINA 1 have?

A

A1AT deficiency

Glu342 = Z variant = 85% enzyme reduction

Glu264Val = S variant = 40% enzyme reduction

wt = M variant

301
Q

What disease and how much enzyme activity does someone homozygous for Glu264Val in SERPINA1 have?

A

A1AT deficiency

Glu342 = Z variant = 85% enzyme reduction

Glu264Val = S variant = 40% enzyme reduction

wt = M variant

302
Q

Progressive childhood hematuria + deafness + anterior lenticonus

A

Alport syndrome

85% XL - COL4A5

15% AR - COL4A3 or A4

  • can have renal failure and retinal findings
  • Contiugous gene delesion on X can cause alport + leiomyomatosis
303
Q

What external and interal differences do you expect between CAIS, PAIS, and 46XY females due to SRY?

A

CAIS/PAIS - complete/partial androgen insensitivty syndrome due to AR mutations

CAIS: 46XY w/ normal external female genetalia and testes w/ blind vaginal pouch

PAIS: 46XY w/ ambiguous genetalia and testes

SRY: 46XY w/ normal female genetalia and ovaries/uterus

- remove testes due to gonadoblastoma risk

304
Q

What % of Angelman syndrome mutations should be detectable by methylation analysis?

A

~80%

70% - deletion of maternal 15q11-13

5% - paternal UPD

5% - imprinting defect

- 10% w/ UBE3A mutations and 10% unknown will be missed

305
Q

When/what should genetic testing in pursued for individuals with autism?

A

If there is intellectual disability: CMA and fragile X

If dismorphic: CMA

If developmental normal -> regression: MECP2

If seizures -> MRI + TSC

Exome role unclear

306
Q

In an adult patient with renal, liver, pancreatic, and splenic cysts and positive family history, what other complications are likely?

A

ADPKD

  • screen for renal function, hypertention, and aneurysms if family history is present
  • CTD: hernias and colonic diverticula are also common
307
Q

What features can help distinguish CFC, Costello, and Noonan w/ multiple lentigenes?

A

CFC: Sparse hair/eyebrows, eczema/ichthyosis

Costello: Papillomata, soft and loose skin w/ deep palmar creases

Noonan w/ multiple lentigenes: Lentigenes + deafness

308
Q

Nail dysplasia, elbow/knee exostosis, V shaped lunula

A

Nail-Patella

LMX1B gene -> regulate COL4A3 and COL4A4

309
Q

What is pseudoachrondroplasia?

A
  • No craniofacial involvement.
  • Normal at birth -> short stature w/ short limbs
  • COMP gene
310
Q

In androgen insensitivity syndrome, what happens in puberty?

A
  • normal breast development - testosterone -> estrogen
  • sparse hair
  • no menses
311
Q

What are the first and second line genetic tests for BWS?

A

1) 11p15.5 methylation -> detects paternal UPD or methylation abnormalitites
2) CDKN1C mutation analysis (5-10%)

312
Q

Name 4 molecular causes of BWS

A

1) epimutation in IC1 (10%)
2) epimutation in iC2 (50%)
3) paternal UPD 11p15 (20%)
4) CDKN1C mutation (10%)

313
Q

What gene causes X linked Charcot Marie Tooth?

A

GJB1 -> connexion 32

314
Q

Retinal degeneration, renal, respiratory, CNS malformation, situs inversus, infertility, liver cysts, diabetes, polydactyly, obesity, skeletal

A

Ciliopathies

315
Q

Compare Male vs Female presentation of 21 hydroxylase deficiency

A

CAH

21 hydroxylase converts 17OH-progesterone into 11 deoxycortisol; deficiency means 17OHP turns into androstenedione -> testosterone instead

Females: Ambiguous genitalia, salt wasting

Males: salt wasting, early puberty

316
Q

What is the definition of a consanguinous relationship?

A

second cousin or closer

317
Q

What is the probability of a recessive disorder in offspring of general public, 1st cousin marriages, and 2nd cousin marriages?

A

general: 2%

2nd cousin: 3%

first cousin: 4%

318
Q

Craniosynostosis w/ severe syndactyly (mitten hands), developmental delay

A

Apert syndrome

FGFR2

319
Q

Craniosynostosis w/ exorbitism (shallow orbits) and hooked nose

A

Crouzon Syndrome

FGFR2

320
Q

Craniosynostosis w/ exorbitism (shallow orbits) and hooked nose

+ Acanthosis nigricans

A

Crouzon w/ Achanthosis nigricans

FGFR3 (Ala391Gln)

321
Q

Most common genetic coronal synostosis

A

Muenke syndrome

FGFR3 (Pro250Arg)

  • May have deafness/brachydactyly/carpal fushion
  • Rule out in ALL coronal synostosis (uni and bilateral)
322
Q

Craniosynostosis w/ cloverleaf skull or broad thumbs/halluces

A

Pfeiffer syndrome

FGFR2 or FGFR1 (rarer, mild)

  • can also have beaked nose and exorbitism like crouzon
323
Q

Craniosynostosis w/ prominent crus, facial assymetry, ptosis, low anterior hairline

A

Saethre-Chotzen

TWIST1 - transcription factor

  • also can have broad thumb -> distinguish from pfeiffer by facial features
  • can be part of 7p21 deletion syndrome + ID
324
Q

craniosynostosis w/ bowed femors, joint anklylosis, radiohumeral synostosis, ambivuous genetalia

A

Antley Bixler

Cytochrome P450 (POR)

325
Q

What does sweat chloride level of 30-60mM mean?

A

Borderline result, most likely atypical CF

<30mM is normal

326
Q

What phenotype is associated with R117H in cis with 5T along with delta F509 in other alelle?

A

Classic

  • 5T = very little expression
327
Q

What phenotype is associated with R117H in cis with 9T along with delta F509 in other alelle?

A

CBAVD

328
Q

Growth retardation, neonatal diabetes -> remission by 1 yr

A

Transient neonatal diabetes

Paternal UPD6

Paternal 6p24 duplication

Methylation defect

ZFP57 inactivation (6p22)

329
Q

Early diabetes, RP, obesity

A

Bardel Biedl Syndrome (with renal disease)

or

Prader Willi

330
Q

Name 2 XL causes of dilated cardiomyopathy

A

1) Dystrophin
2) Barth syndrome (Tafazzin)

331
Q

What does APTX and SETX do?

A

DNA repair genes (SS break and DNA damage response)

  • Ataxia w/ oculomotor apraxia
332
Q

Immunodeficiency, ataxia, small stature, Cell cycle checkpoint inhibitor - Double stranded break repair pathway

A

Ataxia Telangiectasia

ATM

  • Telangiectasias appear by age 4-8
  • Avoid radiation
  • Leukemia/lymphoma/ breast ca risk
333
Q

Butterly rash, immunodeficiency, diabetes, chronic lung disease, Ashkenazi jewish

A

Bloom syndrome

BLM -> DNA helicase -> sister chromatid exchange

334
Q

Deep set eyes w/ pinched appearing nose (loss of subQ fat). hearing loss, RP, photosensitivity

A

Cockayne

CSA, CSB, ERCC6, ERCC8

  • Transcription coupled repair
335
Q

FTT, pancytopenia, cafe au lait spots, radial ray anomalies

A

Fanconi anemia

FANC genes - including BRCA2 (AR), PALB2 (AR)

-broken chromatids and quadriradial formations

336
Q

Trichorrhexis nodosa, short stature, ID, ichthyosis, sun sensitivity

A

Trichothiodystrophy

  • TTDA, XPD
  • DNA repair defect
  • XPD -> decreased B globin production -> B thal trait
337
Q

Corneal clouding, severe sunburn, skin cancers (BCC, SCC, melanoma)

A

Xeroderma Pigmentosum

  • Avoid UV exposure
  • Nucleotide excision repair
338
Q

Large bowel perforation, urterine rupture, carotid dissection, thin translucent skin

A

Vascular EDS

COL3A1 (AD)

339
Q

Widened atrophic scarring, joint hypermobility, hyperextensible skin, molluscoid pseudotumor

A

Classic EDS

COL5A1 (AD)

340
Q

Neonatal hypotonia, premature rupture of membrane, joint dislocation, Globe rupture, congenital kyphoscoliosis

A

Kyphoscoliotic EDS

PLOD1 (AR - NOT a collagen subunit)

341
Q

Genetics of FSHD

A

DUX4 expression

  • Can be due to D4Z4 shortening + PolyA tail haplotype

OR

SMCHD1/DNMT3B variant (methylation controllers)

342
Q

Fragile X premutation is more likely to expand if inherited from mom or dad?

A

mother

343
Q

Screening guidelines for BWS

A

Abd US every 3 months until age 8 -> wilms tumor

AFP every 3 months until age 3 -> hepatoblasoma

344
Q

Short rib, short limbs, cardiac malformation, polydactyly, small nails

A

Ellis- van creveld

ECV and ECV2

345
Q

Short rib, short limbs, polydactyly, renal dysplasia, hepatic fibrosis, retinal degeneration

A

Jeune syndrome

IFT80, DYNC2H1, WDR60, WDR35, TTC21B, WDR19

346
Q

Caniosynostosis, split/ridges in nails, hypertelorism, midline nasal groove.

X-linked Dominant

A

Craniofrontonasal syndrome (Frontonasal syndrome)

EFNB1

XL females more affected because ephrin protein defines cellular boundaries -> cellular interference

347
Q

Craniosynostosis, scalp thickening

A

Bear Stevenson Syndrome

FGFR2

  • Scalp thickness = cutis gyrata
348
Q

What phenotype is associated with R117H in cis with 7T along with delta F509 in other alelle?

A

Non-classic CF

349
Q

Continguous gene deletion involving dystrophin

A

DMD + glycerol kinase deficiency

  • pseudohypertriglyceridemia + high urine glycerol
350
Q

What % of Duchennes is de novo/germline mosiac?

A

De novo: 30%

Germline mosiac: 15%

351
Q

Jemojuvelin (HJV), Hepcidin (HAMP)

A

Juvenile Hemochromotosis

Onset between 10 and 30

352
Q

Neonatal hemochromatosis

A

Autoimmune disease

  • High ferritin, low transferrin, high AFP
  • May present as hydrops
353
Q

HbSC disease

A

Compount HbC and HbS

354
Q

What does 4 nonfunctional Hb A allese cause?

A

Hydrops (no HbA production in utero) - Hb Barts = 4 gamma globins

355
Q

What does 3 nonfunctional HbA alleles cause?

A

HbH disaease

  • Anemia, splenomegaly, hemolyss
356
Q

HbE

A

E26K in B globin

  • abnormal splicing -> decreased B globin synthesis
  • Mild version of B thal when homozygous
  • Severe disease when compound het w/ Beta Thal variant
357
Q

How are hemophilia A and B inherited?

A

Both X linked

358
Q

What is the mechanism of hypocoagulability in von Willebrand Disease?

A

vWF protects factor VIII from premature proteolytic cleavage at sites of vascular injury

359
Q

When should you screen for Pul AVMs in HHT?

A
  • After puberty (rare before)
  • Also between pregnancies (tend to get worse)
360
Q

HTT w/ aortic root dilation and polyps

A

SMAD4

361
Q

ACVRL1, ALK-1, and ENG

A

genes for classic HHT

  • form a homodimeric membraine glycoprotein that is surface receptor for TGFB superfamily
  • SMAD 4 causes HHT w/ polyps and aortic root dilation
362
Q

Isolated Hirschsprung

A

RET

  • 50% familial and 20% sporadic cases
  • Also causes in MEN2A (MTC, pheo, parathyroid) - hirschsprung can be part of this
363
Q

Hirschsprung + upturned ear lobule, deep set eyes, prominent chin, flared eyebrows, microcephaly, ASD, GU anomalies

A

Mowat Wilson

ZEB2

364
Q

Hirschsprung, IUGR, microphcephaly, distal limb anomalies

A

SLOS

DHCR7

  • mother estriol low
  • 2/3 toe syndactyly
365
Q

How does prenatal exclusion testing work?

A

For Huntingtons - a way for at-risk individual to not have HTT child WITHOUT finding out their own status

  • Look at haplotypes of grandparents around HTT gene
  • If haplotype of child is from unaffected grandparent then they are at population risk
366
Q

What features suggest heritable retinoblastoma?

A
  • Bilateral
  • Family history
  • < 1 year old
  • Other ca: Osteosarcomas, melanomas
  • germline RB mutation
367
Q

What should patients with germline RB mutations avoid?

A

Radiation - including radiotherapy

368
Q

>100 colon polyps

Congenital Hypertrophy of RPE

A

APC gene (AD)

FAP: Polyps + CHRPE + Thyroid/duodeum tumors (adenomas)

Gardner: FAP + desmoid tumor, dupernumerary teeth, osteomas

369
Q

>3 hamartomaous polyps, mucocutaneous pigmentation

A

Peutz Jeghers

STK11

  • increased breast, upper GI, ovarian, and pancreas Ca risk
370
Q

Colon, stomach, pancreas, endometrial, ovarian ca, microsatellite instability

  • How do you screen?
A

HNPCC

Mismatch repair

MHL1, MSH2, MSH6, PMS2

  • Colonoscopy at age 20 (or 10 yrs before first ca in family)
  • TVUS at age 30 (or 10 yrs before first ca in family) + Ca 125 every 6-12 months
371
Q

HNPCC + sebaceous adenomas/carcinoma + keratoachantoma

A

Muire Torre

  • MSH2 or MLH1 (subset of HNPCC)
372
Q

Papillomatous papules, macrocephaly, trichilemmomas

+ breast, thyroid, endometrial, renal cancer

A

PTEN - Cowden/BRRS

  • Pigmented macules in penis in BRRS
373
Q

Clear cell renal carcinoma, pheo, endolymphatic sac tumors

  • Tumor suppressor involved in degradation of HIF
A

VHL

374
Q

Hereditary leiomyomatosis and renal cell carcinoma

A

Fumarase (fumarate hydratase) def, AD

375
Q

Renal Cell carcinoma, lung cysts, pneumothorax, fibrofolliculoma, trichodisocoma, acrochordons

A

Birt-Hogg-Dube

FLCN - folliculin

  • Skin, lungs, renal
376
Q

What tumor suppressor gene on ch17 regulates adenylyl cyclase in intracellular cAMP generation?

A

NF1

  • Plexiform Neurofibtromas
  • malignant peripheral nerve sheath
  • optic glioma
  • pheochromocytoma
  • leukemia
  • astrocytomas
  • breast ca
377
Q

Basal cell, jaw cysts, falx calcification

A

Gorlin

PTCH, SUFU (rare)

+ macrocephaly, skeletal abnormalities, medullloblastoma

378
Q

Breast cancer, sarcoma before <45 w/ family hx

A

Li frameni

TP53

Breast ca most common ca in this syndrome (can mimic brca, lynch, other ca predisposition)

379
Q

Hereditary paraganglioma

A

Succinate dehydrogenase

SDHB, SDHC, SDHD

  • part of TCA cycle and complex II
380
Q

SNHL, absent reflexs, acquired microcephaly, skin cancer, sun senstivity, keratitis

A

XP

Nucleotide excision repair

ERCC1-5, XPA, XPC

381
Q

Cell cycle checkpoint kinase that regulates TP53, BRCA1, CHEK2, NBS1

  • Radiation sensitivity

Low IgA, IgE, and IgG levels

  • cerebellar hypoplasia
A

Ataxia Telangiectasia

ATM gene

  • Breast, prostate, and pancreatic cancer
382
Q

Defective double stranded break repair

A

Nijmegen breakage syndrome

NBN

  • microcephaly, FTT, ID, immunodeficiency, lymphoma
  • Heterozygotes at risk for breast and prostate cancer
383
Q

Photosensitivity, microcephaly, immunoglobin deficiency, FTT

DNA Helicase disorder

A

Bloom syndrome

BLM gene -> genomic instability -> abnormal sister chromatid exchange

  • Quadriradials on karyotype
  • many cancers
384
Q

Triangular face, dangling thumbs, imperforate anus, short stature, pancytopenia

A

Fanconi anemia

+ solid tumors and leukemia

  • Chromosome breakage analysis
385
Q

Ribosomal protein disorder

Short abnormal thumbs, cleft palate, macrotytic anemia, increased Hb F

A

Diamond-blackfan anemia

  • associated w/ lung ca, choroid meningioma of the lung, AML, MDS, SSC (vaginal)
386
Q

Parathyroid, pituitary, pancreatic islet ca, adrenocortical tumors

A

MEN1

(MEN1 gene)

  • parathyroid is defining feature (100% of cases)
387
Q

Medullary thyroid cancer, Pheo, hyperparathyroidism

A

MEN2A

RET

  • Test RET in all individuals with MTC
  • Ppx thyroidectomy asap in anyone with RET - 100% penetrance
388
Q

Medullary thyroid ca, pheo, murosal neuroma, ganlioneuromatosis, marfanoid facies, hirschsprung

A

MEN2B

RET

- RET testing in ALL individual with MTC

- Ppx thyroidectomy asap in anyone with RET - 100% penetrance

389
Q

How do you treat familial hypercholesterolemia

A

Statins (consider at age 10)

Aphoresis (for severe homozygotes/cmpd hets)

PSCK9 inhibitors

390
Q

Hypercholesterolemia, phytosterol/sitosterols

A

Sitosterolemia/Phytosterolemia

  • ABCG5, ABCG8 -> twinned sterol-half transporter
  • Increased intestinal absorption/decreased biliary excretion of fish and plant sterols
  • Xanthomas, artheroscerlosis, hemolysis
  • Tx Diet
391
Q

MYBPC3, MYH7, troponin mutations

A

Hypertrophic cardiomyopathy

50% MYBPC3

33% MYH7

Syndromic causes:

  • Fabry (angiokeratoma, short PR)
  • Danon (LAMP2 - pompe like + WPW)
  • Friedreich (+ ataxia)
  • Pompe,
  • Ras-opathies (+ pulmonic stenosis)
392
Q

Eczema, thrombocytopenia, immunodeficiency, lymphoproliferative disease/lymphoma

A

Wiskott aldrich

WASP (XL)

  • regulation of actin cytoskeleton in blood cells

Tx: IVIG, tranfusion, splenectomy, BMT

393
Q

Decreased T cells, hypocalcemia, TOF

A

22q11 del syndrome

  • CD8 primarily affected
394
Q

severe T cell lymphopenia, ear abnormalitites, Coloboma

A

CHARGE syndrome

CHD7

Coloboma, Heart, atresia choanal, retardation (growth and dev), general hypoplasia, ear anomalies

395
Q

Early bacterial infections, low IgG, Low CD19 B cells

A

Bruton agammaglobinemia

BTK gene (XL)

tx: IVIG

396
Q

Albinism, leukocytes w/ giant granules, easy bruising, cognitive delay, ataxia, neuropathy, parkinsonism

A

Chediak Higashi

LYST - lysosomal protein trafficking gene

  • Albinism + immunodeficiency + neuro + easy bruising

Tx: BMT

397
Q

Recurrent fevers, abd pain, joint pain, chest pain

A

Familial mediterranean fever

MEFV (Pyrin)

  • Predisposed to amyloidosis

Tx: Cholchicine

398
Q

What is the risk of disease in child of 1st degree relatives?

A

Genome 12.5% (1/8) IBD

Empiric risk higher than calculated:

30% risk of severe abnormality/death

50% chance of MR or severe abnormality

399
Q

What is the risk of disease in child of 2nd degree relatives?

A

1/16 of genome IBD (6%)

400
Q

What does SURF1 cause/do?

A

Most common genetic cause of leigh syndrome

  • Complex IV assembly
401
Q
  • Upper arms and lower leg (humeroperoneal) weakness
  • achilles, elbow, and spine contractures
A

Emery-Dreifuss muscular dystrophy

STA - XL

LMNA - AD

402
Q

What are the 3 most common genes causing long QT syndrome?

A

KCNQ1, KCNH2 -> LOF

SCN5A -> GOF

  • AD: romano-ward

AR: Jervell and Lange-Nielsen (+ Hearing loss)

403
Q

Which disorders are caused by SCN5A mutations?

A

GOF (AD)-> Romano ward (long QT)

GOF (AR)-> Jervell and Lange Nielsen (Long QT + hearing loss)

LOF (AD) - Brugada -> multiple arrhythmias (incomplete RBBB and ST elevation)

404
Q

What are differences between marfan and LDS?

A

LDS does not have ectopia lentis

LDS has arterial tortuosity, bifid uvula, hypertelorism

405
Q

Crumpled ears, neonatal contractures, scoliosis

A

Beal syndrome (congenital contractural arachnodactyly)

FBN2

406
Q

Prominent eyes, decreased adipose tissue below eyes, thin “pinched” nose, thin lips, hollow cheeks

Thin translucent skin

A

EDS type IV

Vascular EDS

  • COL3A1

+ organ rupture, no hypermobility

407
Q

vitreous gel anomaly, cleft palate, SNHL, arachnodactyly

A

Stickler

COL2, 9, 11

408
Q

Lens dyslocation, thrombophilia, learning disability, cataracts

A

Homocystinuria

Cystathione beta synthase deficiency

409
Q

What are the most common presenting features of MELAS?

A

tRNAleu - A3243G

Mito encephalopathy w/ lactic acidosis and strokes

  • Most common: Diabetes and hearing loss
410
Q

tRNAlys - A8344G

A

MERRF

  • Myoclonic epilepsy, RRF

+ ataxia, dementia, deafness

411
Q

mt T8992G, T8993C

A

NARP

Neurogenic weakness, ataxia, RP

-subset of leigh syndrome

412
Q

What is pearson syndrome?

A

transfusion dependent sideroblastic anemia/pancytopenia

+ malabsorption (exocrine pancreas failure)

  • Mostly mtDNA deletions
413
Q

Homoplasmic mt A1555G, A7445G

A

Deafness when exposed to aminoglycosides

414
Q

Prolonged PR, wide QRS, diabetes, cataracts, long face w/ smooth forehead, pilomatrixoma, distal weakness

A

Myotonic dystrophy type I

3’UTR CTG expansion in DMPK

>1000 - congenital

100-1000 - classic

50-100 - mild

  • 35-50 premutation

<35 - normal

415
Q

Alpha Thal + ID

A

ATRX (XL)

  • Chromatin remodeling that controls a-globin expression in trans
  • also interacts with MECP2 (Rett)
416
Q

In Hemophilia, which lab is abnormal?

A

PTT abnormal

(PT normal)

417
Q

Hyper IgE, eczema, fractures, rough facial skin, coarse facies, denal abnormalities (retain baby teeth)

A

Jobs syndrome

STAT3, DOCK8

  • Severe resp/skin infections
418
Q

When does neural tube closure occur?

A

primary neurulation -> 18-26 days post fertilization

419
Q

2 teratogens that cause Neural Tube defects

A

Valproic acid and maternal diabetes

420
Q

Name the 7 NF1 criteria

A

1) CAL spots: 6+ (0.5cm before puberty, 1.5cm after puberty)
2) neurofibromas: 2+ regular or 1 plexiform
3) Freckling
4) Optic glioma
5) Lisch nodules (2+)
6) Bone: sphenoid dysplasia or thinning of long bone cortex
7) Family history (1st degree relative)

421
Q

CAL spots, intertriginous freckling, lipoma, macrocephaly, learning disability

A

Legious syndrome

SPRED1

  • NF mimicker, but no neurofromas or tumors
422
Q

What finding is common in NF2 but rare in NF1?

A

Deafness

423
Q

What do you need to look for in NF1 patient w/ HTN?

A

Increased risk for renal artery stenosis or pheochromocytoma

424
Q

Low set/posteriorly rotated ears, blue irises, hypertelorism, downslanting palpebral fissures, ptosis, pulmonic stenosis, DD, short stature

A

Noonan: Ras-opathies

Most common: PTPN11 (50%), SOS1 (10%)

Rarer: RAF1, RIT1, KRAS, NRAS,BRAF, MAP2K1

425
Q

Low set/posteriorly rotated ears, blue irises, hypertelorism, downslanting palpebral fissures, ptosis, pulmonic stenosis, DD, short stature, Lentigines, SNHL

A

Noonan with multiple lentigines

PTPN11

426
Q

Low set/posteriorly rotated ears, blue irises, hypertelorism, downslanting palpebral fissures, ptosis, pulmonic stenosis, DD, short stature sparse hair, red with keratosis pilaris, rough skin

A

Cardiofaciocutaneous Syndrome

Noonan + ectoderm

MEK1/2, BRAF, KRAS

427
Q

Low set/posteriorly rotated ears, blue irises, hypertelorism, downslanting palpebral fissures, ptosis, pulmonic stenosis, DD, short stature, papillomas around nose and mouth

A

Costello Syndrome

HRAS

428
Q

Most common gene for parkinsonism before age 40

A

Parkin (PARK2)

429
Q

When can males be affected by MECP2?

A

MECP2 is X linked

  • Males can be affected in Xq28 duplication, mosiacism, or klinefelters
430
Q

Rett syndrome + early epilepsy, marked hypotonia

A

CDKL5 (XL)

  • MECP2 patients usually normal for 12-18 months, then regress
431
Q

Rett syndrome + microcephaly, congenital onset

A

FOXG1 (AD)

  • MECP2 patients usually normal up to 12-18 months, then regress
432
Q

What is the significance of pseudocholinesterase (CHE1) variants?

A

Affect ability to breakd down succinylcholine -> prolonged sensitivity to anesthesia -> paralyzed for days rather than 30 min after surgery

433
Q

What 2 genes cause 70% of malignant hyperthermia?

A

RYR1 and CACNA1S

RYR1 can also cause central core and minicore myopathy

434
Q

What accounts for >90% of pathogenic variants in SMN1?

A

Deletion of exon 7

435
Q

What is the difference between SMN1 and SMN2?

A

Both in chromosome 5

  • SMN2 has a C->T change in exon 7 that leads to decreased splicing efficiency -> 85% transcripts has no exon 7
436
Q

Flat midface with depressed nasal bridge, micrognathia

Midline cleft palate, retinal detachment, hypermobility, SNHL

A

Stickler syndrome

COL2 (AD), 9 (AR), or 11 (AD)

  • Also vitreious anomaly and myopia
437
Q

myopia, cleft palate, SNHL, platyspondyly, ovoid/pear-shaped vertebral bodies, odontoid hypoplasia, flattening and fragmented epiphysis

A

Spondyloepiphyseal dysplasia

COL2A1

  • stickler with more severe skeletal findings
438
Q

What are the common genetic causes of hypercoagulability (thrombophylia?)

A
  • Factor V leiden
  • Prothrombin mutation (factor II leiden)
  • Antithrombin 3 deficiency
  • Protein C or S deficiency
  • Homocysteinuria
439
Q

R506Q FV

A

Factor V leiden

  • most common thrombophilia - 20% of all idiopathic thrombosis and 60% in pregnancy
  • R506Q -> resistance to activated protein C cleavage
440
Q

FII 20210A mutation

A

Factor II Leiden (Prothombin mutation)

441
Q

What does protein C and S do?

A

Protein C destroys factors V and VIII -> inactivates clotting

Protein S is Vit K dependent cofactor for protein C

442
Q

What is the workup for inheritled thrombophilia?

A
  • Genetic testing for Factor V leiden (R506Q) and prothombin mutation (20210A)
  • Functional testing for Protein C, S, and antithrombin III (genetically heterogeneous)
  • Homocystein level
443
Q

How do you manage pregnant patients with factor V leiden?

A

Factor V leiden is AD w/ incomplete penetrance

  • Heterozygotes at 2-3x risk -> monitor closely
  • Homozygotes (and prothrombin mutations patients) should get VTE prophylaxis during pregnancy
444
Q

What is the pathophys for TSC?

A

Hamartin (TSC1) and Tuberin (TSC2) are tumor suppressor genes that form heterodimer -> regulates PI3K signaling and inhibits mTOR -> Regulates cell growth/proligeration

  • 2 hit hypothesis for individual neoplasms
445
Q

Hypomelanotic macules, raised leathery patches, angiofibromas, retinal hamartomas, SEGA, renal angiomyoplipomas, lymphanioleiomyomatosis

A

TSC

Tuberin and Hamartin (AD)

Hypomelanotic macule = ash leaf spot

thickened, leathery “orange peel” like skin = shagreen patch

  • Renal angiomyolipomas common
  • Get chest CT for Lymphangioleiomyomatosis
446
Q

What are ages of onset for XALD and XANM?

A

ALD - 3-10 years

ANM - 20-40 years

447
Q

What dose ABCD1 gene cause?

A

XALD

  • VLCFA elevated (C26:0 lysophosphatidylcholine)
  • Carriers also have VLCFA elevation
  • Tx: BMT, HSCT early, Lorenzo’s oil (Oleic and erucic acid)
448
Q

What are oleic and erucic acid?

A

Lorenzo’s oil -> improve VLCFAs in XALD; may slow disease progression, clinical utility unclear

449
Q

Marfanoid + mucosal neuromas

A

MEN2B

Rett

450
Q

Drugs to void in mitochondrial disease

A

VPA

Aminoglycosides

Metformin

Barbiturates

Tetracycline

Zidovudine

451
Q

DMPK expansion is more likely in to occur in which patient?

A

Maternal

452
Q

How long do you need to take folic acid to prevent NTD during pregnancy?

A

Until 12 weeks

453
Q

occipital encephalocele, bilateral large kidneys w/ multicystic dysplasia, polydactyly

A

Meckel syndrome

ciliopathy

MKS1, MKS2,

454
Q

Which Rasopathy often has hearing loss?

A

Noonan w/ multiple lentigines

PTPN11

455
Q

Phenotype for homozygotes w/ PMS2, MLH1, MSH2, MSH6

A

NF-like syndrome

Homozygotes for Lynch

  • CALS, Freckling, multiple GI cancers
456
Q

hypomelanocytic macules, raised leathery patch, angiofibromas, ungual fibromas

A

TSC

457
Q

Prenatal finding in TSC

A

Cardiac Rhabdomyoma

458
Q

Most common tumor in TSC

A

angiomyolipoma

459
Q

What genes are associate with increased risk for triple negative breast ca?

A

BRCA1, BRCA2, PALB2

460
Q

What is the significance of serous papillary cystadenocarcinoma?

A

Ovarian tumor seen in BRCA1 and BRCA2

461
Q

What is the definition of high risk for breast cancer?

A

Lifetime risk >40% from age 20

Moderate is lifetime risk >20% from age 20

462
Q

What screening should be offered to women w/ increased risk for breast cancer?

A

Always - breast awareness

Age 30 - MRI (20 for tp53)

Age 40- mammo (avoid in tp53)

  • U/S if MRI/mammo should be done but not suitable/tolerated
463
Q

AR condition that is on DDx for multiple polyposis

A

MUTYH associated polyposis

Check if APC/STK11 are negative

464
Q

Macrocephaly, GI polyps, Autism, lipoma, trichilemmoma, oral papilloma, AVM, hemangiomas

A

Cowden

PTEN

465
Q

Cerebellar dysplastic gangliocytoma, trichilemmoma, breast cancer

A

Cowden

PTEN

466
Q

What are the major tumors in PTEN syndromes?

A

Breast, Thyroid, and Uterine - benign or malignant

  • Colon (polyps), Renal cell
467
Q

>100 polyps, desmoid tumor, osteoma, supernumery teeth

A

FAP

APC gene - null/nonsense/frameshift variants

  • screen for polyps at age 10
468
Q

What do missense variants in APC cause?

A

benign unless splicing is affected

  • FAP mutations are null/nonsense/frameshift
469
Q

What is the significance of MUTYH?

A

Phenocopy of FAP that is AR

  • >9 colon adenomas with no AD family history
  • DNA oxidation damage repair
470
Q

Surveillance for FAP

A
  • Colon screening at 10
  • Consider colectomy before 20
471
Q

What gene is associated with linitis plastica and lobular breast cancer?

A

CDH1 (E-cadherin)

Hereditary Diffuse Gastric Cancer

  • Gastric and lobular breast ca
472
Q

Palmar/Plantar pits, cerebral falx calcifications, odontogenic keratocyst/polyostic bone cyst, BCC

A

Gorlin Syndrome

PTCH1 (AD), SUFU (AD)

+ macrocephaly, clefting, polydactyly, ovarian fibroma, medulloblastoma, cataracts

473
Q

>5 juvenile polyps in colon/rectum

  • Juvenile polyps in intesting/upper GI tract
A

Juvenile polyposis

  • BMPR1A (TGFB pathway) - isolated
  • SMAD4 (TGFB pathway) - w/ HHT
  • PTEN - w/ Cowden
  • PTCH - w/ Gorlin
474
Q

Juvenile polyposis + HHT

A

SMAD4

475
Q

Juvenile polyps + macrcephaly, trichilemmoma, freckling

A

PTEN

476
Q

Juvenile polyps + BCC

A

Gorlin

PTCH1

477
Q

What gene accounts for non-syndromic juvenile polyposis?

A

BMPR1A

478
Q

Screening for juvenile polyposis

A

Colonoscopy at 15

EGD at 25

479
Q

What type of variants in APC result in FAP?

A

Null/nonsense/frameshift

  • Missense only if splicing
480
Q

What does BRAF presence in colon cancer cells mean?

A

Most likely sporadic (not common in lynch syndrome)

481
Q

Surveillance for Cowden

A

Thyroid at 16

Breast MRI at 30

Colonoscopy at 35

Renal US at 40

482
Q

desmoid tumors, papillary thyroid, supernumerary teeth, adrenal gland adenomas, osteomas, medulloblastoma

A

Extra-colonic features of FAP

483
Q

Protein-losing enteropathy, macrocephaly, juvenile polyposis, hypotonia

A

10q23 deletion

  • Includes PTEN and BMPR1A
484
Q

Breast ca, leiomyosarcoma, adrenocortical tumor, wilms tumor, phyllodes tumor

A

Li Frameni

TP53

  • Adrenocortical and phyllodes highest absolute risk increase
485
Q

How does EPCAM cause Lynch Syndrome?

A

EPCAM is next to MSH2, large deletion canl ead to epigenetic silencing of MSH2 -> colorectal cancer

486
Q

What is Muir-Torre Syndrome?

A

Any interal cancer (colon usually) + sebacious skin tumor (epithelioma, ednoma, carcnioma)

  • most commonly due to Lynch, but not always
487
Q

What is turcot syndrome?

A

Polyposis + primary brain tumor

  • Usually APC or Lynch gene
488
Q

How do you interpret microsatellite instability from a somatic tumor sample?

A
  • MSI is common in sporadic colon cancers -> low PPV for Lynch, but high NPV
  • MSI is rare in extra-colonic cancers -> high PPV for lynch in ovarian, endometria, gastric cancers
489
Q

What drug reduces risk of colon cancer in lynch syndrome?

A

Aspirin

490
Q

What is the pathophys of MEN1 and MEN2?

A

MEN1 - Menin - tumor suppressor gene

MEN2 - Ret - GOF in proto-oncogene

491
Q

Blue nevi and lentigenes, schwannoma, atrial myxoma, pitruitary tumor, thyroid cancer

A

Carney Complex

PRKAR1A

492
Q

Surveillance for MEN1

A
  • clinical for endocrine issues
  • Annual calcium and prolactin starting at age 5
493
Q

When is thyroidectomy recommended in MEN2?

A

MEN2A - 5yo

MEN2B -early as possible -> metastasis can happen by age 2

494
Q

Meningioma, glioma, posterior subcapsular lenticular opacities, cerebral calcifications, schwannomas

A

NF2

  • Merlin - tumor suppressor gene

Criteria:

  • bilateral vestibular schwanomma
  • 1st degree relative w/ NF2 + Unilateral schwanomma + other tumors
  • Unilateral schwanomma + 2 other tumors
  • multiple meningiomas + other tumors
495
Q

What genes account for the majority of genetic ovarian cancer?

A

BRCA1, BRCA2, Lynch account for majority

  • BRIP1, RAD51C, and RAD51D also associated
496
Q

GI intussusception, perioral freckling

A

Peutz-Jeghers

STK11

  • Polyps tend to be large and pedunculated -> often lead to intusscuception
  • Get baseline EGD and colonoscopy at 8yo

+ Stomach, breast, colon, pancrease, ovarian cancer

497
Q

Name 3 genes associated with pheochromocytoma

A

VHL (+ hemangioblastoma)

SDHB, SDHD (+ paraganglioma)

RET (+ medullary thyroid carcinoma)

498
Q

Pheochromocytoma + marfanoid body habitus

A

MEN2B

+ medullary thyroid

499
Q

RCC + fibrofolliculoma, pneumothorax

A

Birt-Hogg-Dube

FLCN - folliculin

+ pulmonary cysts

500
Q

RCC + hemangioblastoma

A

VHL

+ pheo

501
Q

RCC + paraganglioma

A

SDH

+ pheo

502
Q

RCC + fibroids

A

Fumarase deficiency

  • Fibroids = leiomyomatosis
503
Q

What is the most common second hit in RB?

A

Loss of heterozygosity

504
Q

What is “Trilateral RB”?

A

Bilateral RB + pinealblastoma (common in RB as part of primary cancer)

505
Q

What are the major secondary cancers in RB?

A

Osteosarcoma, soft tissue sarcome, melanoma, brain tumors

506
Q

What clinical test should be offered to parents of children affected by RB?

A

Eye exam to look for spontaneously regressed retinoblastoma

507
Q

Surveillance for RB1

A

Eye exam under anesthesia from 3 weeks to 3 years

508
Q

What are the most common manifestation of VHL?

A

Retinal angiomatosis > cerebellar hemangioblastoma > RCC > pheo

509
Q

When should you start surveillance in VHL?

A

Eye exam at 5

Pheo at 11 (Urine VMA or plasma metanephrines)

MRI brain + body at 15

510
Q

11p13 deletion

A

WAGR

  • Wilms, aniridia, GU, retardation

WT1 and PAX6 included

511
Q

Wilms tumor, GU anomaly, renal impairment (Mesangial sclerosis)

A

Denys-Drash

  • WT1
512
Q

Wilms tumor, gonadoblastoma, renal impairment (FSGS)

A

Frasier syndrome

WT1 mutations intron 9 -> splicing isoform change

513
Q

How do you screen for wilm’s tumor in at risk individuals?

A

Abdominal US every 3-4 months until age 7-8

514
Q

What testing needs to be checked after diagnosing 22q deletion?

A

Endo: Calcium, TSH, PTH

Immunology: T cells (do not give live vaccine until T cells are normalized), platelets

Cards: TTE, ECG

Other: Eye exam, audiology

515
Q

Phenotype for 47, XXX

A

tall stature, slightly lower IQ (avg 10-15 points lower)

516
Q

Azoospermia, undescented testes, hypergonatotrophic hypogonadism w/ low testosterone, gynecomastia, language delay

A

Klinefelter 47 XXY

517
Q

what is the most common mechanism for 47 XYY?

A

non-dysjunction in paternal meiosis II

518
Q

How much autosomal imbalance can a fetus tolerate in most cases?

A

2% monosomy (~60Mb) or 4% trisomy (!120Mb)

519
Q

t(11:22)(q23;q11)

A

Most common recurrent non-robertsonian translocation

  • Can lead to 3:1 segregation -> duplication of 22q10 and 11q23 -> emmanual syndrome (FTT, microcephaly, hypotonia, DD, renal issues)
520
Q

3/4 finger syndactyly + clinodactyly, 2/3 toe syndactyly + bulbous toes

Body assymetry, ID, streaky skin hyper/hypopigmentation

A

Mosaic diploidy/triploidy

521
Q

Large forehead, high hairline with sparse hair over temples

Large mouth and full philtrum

A

Pallister Killian

Mosaic tetrasomy 12p

522
Q

Deep longitudinal creases on soles of feet

Absent/hypoplasic patella

Finger contractures

A

Mosaic trisomy 8

  • also look for heme malignancies
523
Q

Preauricular tags, ear malformations, CHD, renal atresia, radial ray defects

A

Mosaic trisomy 22

524
Q

Name the 7 chromosomes that cause imprinting syndromes

A

6, 7, 11, 14, 15, 16, 20

525
Q

Most common terminal deletion syndrome

A

1p36 del

  • DD, seizures, hypotonia, deep set eyes, straight eyebrows, delayed fontanelle closure, clefts
526
Q

Iris coloboma, sagging everted eyelids, short nose, very short phlitrum, seizures

A

Wolf Hirschorn

4p del

527
Q

5p terminal deletion syndrome

A

Cri Du Chat

  • cat like cry, DD
528
Q

4p terminal deletion syndrome

A

Wolf-Hirschhorn

  • Greek warrior helmet face, coloboma, seizures, FTT
529
Q

16p terminal deletion syndrome

A

ATR

  • HbH (1/4 alpha thal) + mental retardation
530
Q

17p terminal deletion syndrome

A

Miller Dieker

  • LIS1 + microcephaly, MR, dysmorphic
531
Q

Xp terminal deletion

A

SHOX, KAL

  • Short stature + syndromic
532
Q

What is the major factor in increased mortality in infancy for patients with down syndrome?

A

Congential heart defects

533
Q

What is the risk of having a liveborn child with down syndrome when a parent has (14:21) robertsonian translocation?

A

1% if paternal

10-15% if maternal

100% if either parent is t(21:21)

534
Q

Short sternum, IUGR, prominent occiput, simple ears, overriding fingers, nail hypoplasia, rocker bottom feet, pale fundi

A

Edwards syndrome

Trisomy 18

+ polyvalvular dysplasia

535
Q

What factors increase the chances of abnormal offspring for parents with paricentric inversion?

A

large inversions -> most likely to recombine, recombination results in smaller areas of del/dup -> more likely viable

536
Q

scaphocephaly (dolichocephaly), digital contractures, hemiertebrae, renal anomalies, deep plantar creases

A

Mosiac trisomy 8

  • Male > female
  • Cell line disappears in lymphocytes -> check fibroblasts
537
Q

What is the most common trisomy in abortuses?

A

Trisomy 16

538
Q

What is the most common issue in management of patau syndrome?

A

GERD

  • Aspriation -> cardiopulmonary arrest common COD
539
Q

What is the ring chromosome phenotype?

A

Phenotype from all ring chromosomes due to mitotic instability (dyanamic mosaicism) in addition to specific imbalance issues

  • FTT, microcephaly, ID, dysmoprhic features
540
Q

What does Ringed X cause?

A

If large -> XIST present -> mosaic turner

If small -> XIST absent -> X disomy -> severe ID

- Need to do FISH to look for XIST

541
Q

What are the common robertsonian translocation?

A

13;14 and 14:21

542
Q

What are the main phenotypes assocaited with robertsonian translocation?

A

Trisomy 21

Trisomy 13

UPD 15 (PWS, AS)

UPD 14 -

Mat: Temple Syndrome - hypotona, FTT, DD, macrocephaly, small hands/feet

Pat: Kagami-Ogata Syndrome - coat hanger ribs, bell shaped thorax, hairy forehead

543
Q

What does idic(15) cause?

A

isodicentric chromosome 15

  • normal if PW/AS region (q11-13) is not involved
  • most commonly DD and epilepsy
544
Q

What does idic(22) cause?

A

Isodicentric 22

Cat eye syndrome

  • Coloboma, ear tags/pits, anal anomalies, TOF/TAPVD, renal atresia, DD
545
Q

If a supernumery marker chromosome is detect prenatally, what features make it more likely to cause abnormality in fetus?

A
  • de novo
  • large
  • contains euchromatin (seen on array)
  • ring
  • may cause UPD in 15
546
Q

How do you screen for breast ca in Li frameni

A

MRI at age 20

Avoid mammograms (radiation increases risk)

547
Q

Which Lynch genes have less severe phenotypes

A

PMS2, MSH6

MLH1 and MSH2 = classic

548
Q

What does MLH1 promoter methylation tell you?

A

More likely for tumor to be sporadic (vs Lynch)

549
Q

Treatment for schwannomas in NF2

A

VEGF inhibitor

Bevecizumab

550
Q

NF2 surveillance

A

Hearing and Eye - childhood

MRI in early teens and adulthood

551
Q

What kind of ovarian cancer is seen in BRCA1/2?

A

Serous ovarian

  • Non serous is seen in Lynch
552
Q

What is olaparib

A

PARP (poly ADP ribose polymerase) inhibitors

  • Targeted therapy for BRCA1/2 related breast, ovarian, pancreatic cancer
553
Q

Surveillance for Peutz Jeghers syndrome

A
  • Baseline EGD/colonoscopy at 8 (prevent intussiception) -> If no polyps screen every 3 years at 18
  • Breast MRI at 25
554
Q

What is significance of HOXB12 gene?

A

Causes isolated prostate cancer

555
Q

What is the mechanism of triploidy?

A

Digynic: 2nd polar body incorporated into fertilized oocyte

Diandric: 2 sperm, 1 egg -> big placenta

  • Big placenta = high B HCG (chart is wrong)
556
Q

Where is beta HCG secreted from?

A

Placenta

557
Q

What is the health risk associated with partial or complete hydatiform mole?

A

Malignant transformation into choriocarcinoma

558
Q

what is 45,X/46,X,r(X) mean?

A

Mosaic ringed X

If XIST present -> Mosaic turner

If XIST absent -> severe MR due to X disomy

559
Q

2 most common features of Turner Syndrome

A

Short stature and gonadal dysgenesis

560
Q

What phenotype(s) are unbalanced X-Autosome translocations associated with?

A
  • abnormal X selectively inactivated
  • Males infertile
  • Females sometimes infertile
  • Increased risk for hypomelanosis of ito
561
Q

omphalocele, polyhydramnios, macroglossia

A

Beckwidth Weidemann Syndrome

562
Q

Telephone receiver femurs, short limbs

A

Thanatophoric dysplasia

FGFR3

563
Q

Prenatal US: undermineralization of skull

A

Infantile hypophosphatasia or OI

564
Q

Prenatal US: bowed limbs

  • Maternal virizliation
A

Antley bixler

POR

565
Q

Congenital diaphragmatic hernia, cutis aplasia

A

Trisomy 13

566
Q

Congenital diaphragmatic hernia, overlapping digits

A

Trisomy 18

567
Q

Congenital Diaphragmatic hernia, prominent philtrum, rhizomelia

A

Pallister Killian

Mosaic isochromosome 12p

568
Q

Congenital diaphragmatic hernia, limb reduction defects, microbrachycephay, depressed nasal bridge with anteverted nares, long smooth philtrum, micrognathia

A

CDLS

NIPBL

569
Q

Congenital Diaphragmatic hernia, short distal phalanges, cleft L/P, genital malformation

A

Fryns Syndrome

570
Q

Congenital diaphgramatic hernia, heart defect, polydacylty, overgrowth

A

Simpon Gloabi Behmel

GPC3 (XL)

571
Q

What does fetal fluconazole exposure cause?

A

Antley Bixler phenocopy

  • Fluconazole inhibits CYP450 oxoreductase (POR)
572
Q

short palpebral fissures, flat midface, long/flat philtrum, thin vermilion of upper lip

A

Fetal Alcohol Syndrome

  • low birthweight, microcephaly, DD
573
Q

which antiepileptic exposure in utero can lead to hypoplastic nails?

A

Carbamazepine

574
Q

Which antiepileptic in lead to NTD when exposed in utero?

A

VPA

575
Q

3 most likely outcomes after fetal US showing echogenic bowel

A

1) normal
2) Trisomy 21 (3rd if screening is negative)
3) Cystic fibrosis

576
Q

Most common cause of low maternal estriol

A

Steroid Sulfatase Deficiency

STS gene - 90% deletions

X-linked ichthyosis

  • DDX: SLOS (DHCR7), Antley Bixler (POR)
577
Q

What are the teratogenic effects of phenylalanine?

A

Microcephaly, ID

CHD: TOF, aortic coarct

Dysmorphic (similar to fetal alcohol) - long/smooth philtrum w/ thin upper lip, micrognathia, maxillary hypoplasia, flattened nasal ridge, epicanthal folds

Goal: <360umol/L

578
Q

What percent of miscarriages have a chromosomal abnormality?

A

50%

579
Q

What is the first line treatment for homocystinuria?

A

Pyridoxine (B6) -> some are responsive

580
Q

what are the most common causes of increased fetal nuchal translucency?

A

1) Cardiac malformation - get fetal echo
2) Chromosomal (Turner, Down syndrome)
3) Hemoglobinopathies

581
Q

What are the main components of Potter synquence?

A

Oligohydramnios -> micrognathia, pulmonary hypoplasia, postural anomalies (talipes)

582
Q

micrognathia, pulmonary hypoplasia, talipes, renal cysts

A

ARPKD

renal cysts + potter sequence

583
Q

micrognathia, pulmonary hypoplasia, talipes, occipital encephalocele, enlarged kidneys, liver fibrosis

A

Meckel syndrome

MKS1, TMEM67, CEP290, RPGRIP1L -> ciliopathy

  • Potter sequence + encephalocele + renal/liver disease
584
Q

micrognathia, pulmonary hypoplasia, talipes, branchial fistula, ear anomalies

A

Brachial-oto-renal syndrome

EYA1 (AD)

Potter sequence = renal disease

585
Q

micrognathia, pulmonary hypoplasia, talipes, cryptophthalmos, laryngeal stenosis, syndactyly

A

Fraser Syndrome

FRAS1, GRIP1, FREM1/2

potter sequence (renal) + cryptophthalmos + laryngeal stenosis

586
Q

What GALT variant is most likely to lead to premature ovarian failure?

A

Classic: Q188R/Q188R

587
Q

What does congneital rubella look like?

A

Exposure in utero from 2-10 wks

  • IUGR
  • Microcephaly

- RP

- SNHL

  • PDA, pulmonary artery stenosis
588
Q

What does congenital CMV look like?

A

IUGR

Microcephaly, abnormal CT (Calcifications)

Jaundice, HSM, elevated ALT

Petechiae, purpora, thrombocytpenia, anemia

589
Q

Which syndromes can have bilateral radial ray defects?

A

Fanconi anemia and trisomy 18

590
Q

Short femur on prenatal US + low maternal estriol

A

SLOS

591
Q

How does congenial toxoplasmosis present?

A

microcephaly, CNS anomalies, chorioretinitis

592
Q

Compare locations of cysts in ARPKD vs ADPKD

A

ARPKD: Multiple small cysts in collecting ducts

ADPKD: Fewer, large cysts, in nephron or collecting duct

593
Q

How does polycystic kidney disease present on prenatal US?

A

Large, Hyperechogenic kidneys +/- oligohydramnios

594
Q

How does fetal varicella present?

A

Skin, CNS, and limb changes

595
Q

Agenesis of corpus callosum, hydrocephalus, ID, adducted thumbs, spastic paraplegia

A

X-linked hydrocephalus

L1CAM

596
Q

Which phase of prophase 1 is meiosis arrested in for females?

A

Diplotene

Pachytene is where recombination happens

597
Q

acute megakaryoblastic leukemia

A

Cancer seen in down syndrome

598
Q

What does NOTCH 1, 2, and 3 cause?

A

NOTCH1 - Adams oliver - cutis aplasia + transerve limb defects

NOTCH2 - Alagille

NOTCH3 - CADASIL

599
Q

Coat hanger ribs, bell shaped thorax, hairy forehead

A

Kagami Ogata

Paternal UPD 14

600
Q

Hypotonia, short stature, macrocephaly, small hands/feet

A

Temple syndrome

Maternal UPD 14 - paternally expressed genes

601
Q

What malfromation is young maternal age associated with?

A

Gastroschisis

602
Q

What GSDs can present as fetal akinesia?

A

GSD4 - polyglucosan buildup

GSD7 - muscle

603
Q

How much folic acid should a pregnant woman take?

A

0.5mg all comers

5mg if history of NTD or on anticonvulsants

604
Q

what % of hypoplastic left heart is syndromic?

A

5%

  • 20% will have other findings on ultrasound, but not necessarily syndromic
605
Q

What heart defect is maternal diabetes associated with?

A

Hypoplastic left heart

606
Q

When you can accurately determine fetal sex on U/S

A

13-14 weeks

  • hard to see 12 weeks or before
607
Q

What is the easliest you can do NIPT?

A

8 weeks

608
Q

What chromosomal testing should you do if you find isolated prenatal gastroschisis, unilateral multicystic dysplasic kidneys, or talipes?

A

None; not associated with chromosomal abnormalities.

609
Q

When is the right time to do CVS/Amnio?

A

CVS - 11-13 weeks

Amnio - 15-17 weeks

610
Q

Failure to progress in labour, prolonged labor, prolonged gestation

  • low maternal estriol
A

Steroid Sulfatase deficiency

STS gene - 90% deletions

XL

611
Q

which aneuploidies are NOT associated with advanced maternal age?

A

Triploidy, 45,X ,47XYY

612
Q

What malformation has highest increased RR in maternal diabetes? What is most common?

A

Caudal Regression > Laterality disturbance > NTD

Most common: NTD > CHD > CL/P

613
Q

What is fragment size of fetal DNA at NIPT?

A

160-340bp

614
Q

What organ defect should you associate with oligohydramnios? polyhydramnios?

A

Oligo -> renal (cannot produce urine)

Poly -> GI ( cannot swallow)

615
Q

Polyhydramnios, macrosomia, maternal glucose intolerance

A

BWS

616
Q

what % of women with fragile X prematutation have POF?

A

20%

617
Q

post-auricular lymphadenopathy

A

Congenital Rubella

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