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FRACP 2023 Cram Homicrons Edition > Genetics/Syndromes > Flashcards

Genetics/Syndromes Flashcards

1
Q

CHARGE

A

CHARGE syndrome.
CHD7 gene- most sporadic
C (coloboma)
H (congenital heart defects)
A (choanal atresia)
R (retardation of growth/developmental)
G (genital anomalies)
E (ear anomalies or deafness.)

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2
Q

VACTERL association

A

VACTERL
- Due to disruption in early embryogenesis

V (vertebral defects)
A (anal atresia)
C (cardiac defects)
T (tracheo-oesphageal defects)
R (renal anomalies)
L (limb abnormalities.)

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3
Q

Rubenstein-Taybi

A

Microdeletion chromosome 16
- Short stature
- Mod-severe ID
- Broad fingers/toes gap
- Facial features as per pic

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4
Q

DiGeorge

A

CATCH22

2q11.1 deletion syndrome

C- heart defects
A-
T- Thymic hypoplasia, absent T/B cells
C- Cleft palette
H- Hypocalcemia
poor immune system function, cleft palate, hypocalcaemia and delayed development.

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5
Q

Loeys-Dietz

A

AD/75% de novo
SMAD3, TGFB

Overview: cardiac aneurysms, joint laxity, bifid uvula

Aneurysms/dissections
Pectus excavatum/carinatum, scoliosis, joint laxity,arachnodactyly/talipes, C-spine malformations
BIFID UVULA, wide spaced eyes, craniosynostosis
Skin: translucent/easy bruising

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6
Q

Homocysteinuria

A

AR- CBS mutation, intermediate in methionine → cysteine

Overview: joint contractures, inferior lens dislocation, low IQ, stroke risk

B6 responsive (mild/unresponsive)

Ectopia lentis (downward), tall stature/long limbs, pectus, scoliosis, CVA/VTE, dev delay/ID

Ix: elevated total homocys/met
Rx: B12/folate, met restricted diet

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7
Q

Marfans

A

AD, FBN1 gene, 25% denovo

Overview: joint laxity, superior lens dislocation, normal IQ

Ectopia lentis (sup) 50-80%
Aortic root dilatation/MVP/TVP
Skeletal overgrowth, arachnodactyly, joint laxity, scoliosis
High arched palate, retrognathia
N IQ

Score: Ghent criteria >7 to diagnose

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8
Q

Shprintzen-Goldberg syndrome

A

Craniosynostosis
Narrow head, hypertelorism, high arched palate, micrognathia, Marfanoid body habitus
Delayed development/ID
Poor tone, umbilical hernias

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9
Q

Types of genetic tests overview

A

Chromosomal testing
- Cytogenetics: karyotype
- Molecular cytogenetics: microarray, FISH, MLPA

Imprinting
- DNA methylation studies

Known mutations
- Single gene analysis
- SNP array
- MLPA

Unknown mutations
- NGS, WES, Sanger sequencing (slow)

Trinucleotide repeat analysis
- For TNA disorders i.e DMD, FXS
- Amplify DNA then Southern blot

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10
Q

When to use different genetic tests

A

Gene defects
- Microarray: duplications or deletions, unbalanced/microdeletions
- Karyotype: aneuploidies, sex chromosomes, translocations
- SNP array (single nucleotide polymorphisms): consanguinuity/wide genome screen
- FISH- microdeletions/duplications, need to have idea of gene that youre looking for
- MLPA- PCR amplification in area of interest- small deletions/duplications

Imprinting/TNA:
- Triplet repeat analysis: PCR then southern blot
- Methylation studies: UPD (if neg = imprinting)

Unknown
- NGS, WES

Other:
-Chromosomal breakage test: Fanconi, hereditary spherocytosis, AT

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11
Q

What do S,N,W Blots look for?

A

Blots (SNoW DRoP)
Southern = DNA
Northern = RNA
Western = Protein

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12
Q

Broad genetic screening tests- types of sequencing?

A

Sanger sequencing: screening for unknown mutation

Whole exome sequencing (WES)
- Exons (coding regions)
- Slower than targeted panels
- Can identify genes responsible for pathology

Next Gen Sequencing/whole genome
- All genes, translocations and non-coding DNA
- Cannot detect triplet repeats pr methylation defects

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13
Q

Types of cytogenetics, method and role?

A

Cytogenetics
Can identify: aneuploidies, large chromosomal imbalances, balanced/unbalanced translocations

(NOT- single gene, microdeletions, triplet repeat, imprinting)

Karyotype: directly analyses whole chromosomes
- Used for trisomies/monosomies- T21, Klinefelter/Turner

Molecular cytogenetics
Microarray
Can identify: gains/losses in genetic material
- CGH: compares DNA from 2 sources
- SNP: compares to control, can detect heterozygosity (more information)
uses: microdeletion/dup, single gene diagnoses

FISH
Can identify: presence/absence of DNA sequences on chromosomes, balanced rearrangements, localisation of DNA targets
i.e Trisomy, microdup/del- DiGeorge, Williams

MLPA
Can identify: duplication/deletions- amplifies DNA and seperates based on size

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14
Q

Klinefelters- 47XXY

A

Non-disjunction of X chromosome in meitotic division
1 in 800-1000 males
More common than turners

Breast tissue, wide hips, & euchanoid habitus- increased height/clinodactyly, reduced muscle bulk
Reduced libido/decreased fertility, testes smaller, may have hypogonadism
Language disabilities/ADHD, shy/depression
55% MVP

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15
Q

Ocular albinisim OA1

A

X-linked disorder
- Limited eye disease
- Poor vision/nystagmus
- Mums (carrier) may also have ocular albinism/mosaicism

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16
Q

Tietz syndrome

A

-MITF gene mutation (also seen in Waardenburg)
- Heterochromia/greying of hair
- Pale blue eyes/blonde hair
- Congenital deafness
- Hair colour may change

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17
Q

Waardenburg syndrome

A
  • Heterchromia, white forelock
  • SNHL with normal external eat
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18
Q

Jervell-Lange-Neilsen

A

Deafness/SNHL & long QT

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19
Q

Usher syndrome

A

SNHL & normal external ear
Retinitis pigmentosa

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20
Q

Pendred syndrome

A

SNHL, normal external ear
Hypothyroidism

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21
Q

Alport syndrome

A

COL2
Haematuria/nephritis
SNHL & normal external ear
Anterior chamber eye abnormalities

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22
Q

Chediak-Higashi Syndrome

A

Disorder of vascular trafficking (AR) Partial oculocutaneous albinism
Recurrent pyogenic infections
- Will develop HLH
Coagulopathy
Neurological abnormalities

Ix: giant cytoplasmic granules in leucocytes/platelets - pathognominic

Rx: HSCT- does not fix eye/skin/neuro abnormalities

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23
Q

Vici syndrome

A

-Congenital agenesis of the corpus callosum
- Bilateral cataracts
- Hypopigmentation of skin and hair
- Cardiomyopathy
- Immunodeficiency

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24
Q

Griscelli syndrome

A

Disorder of vascular trafficking (AR)
RAB27a gene

  • Sparse/hypopigmented hair
    Oculocutaneous albinism
  • Neutropenia
  • NO giant granules
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25
Q

Hermansky-Pudlak syndrome

A

AR
Oculocutaneous albinism
Visual impairment
Platelet dysfunction and prolonged bleeding
Abnormal storage of a fatty-like substance (ceroid lipofuscin

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26
Q

Norrie Disease

A

X linked
- Microcephaly
- Bilateral retinal dysplasia
- Neuropsychiatric symptoms.

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27
Q

Incontinentia Pigmenti

A

X-linked recessive (lethal in males, only females affected)
- Skin lesions (hypopigmented initially)
- Retinal dysplasia

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28
Q

Inheritance patterns
- Autosomal dominant

A

Males and females
Every affected person has at least one affected parents
3/4 children affected

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29
Q

Inheritance patterns
- Autosomal recessive

A

Increased in consanguinity
Males and females
Parents not affected (carrier 1/4)- skips a generation

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30
Q

Inheritance patterns
- X-linked dominant

A

Mum to all sons
Males often die/females affected
All daughters of affected male will receive gene

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31
Q

Inheritance patterns
- X-linked recessive

A

Mum to all sons
Females NOT affected
All daughters of affected male will receive gene

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32
Q

Inheritance patterns
- Translocation

A

Phenotypically normal carrier with increased risk of miscarriages or abnormal offspring (both males and females)

Reciprocal: break into two parts and exchange
Robertsonian: fusion of two short arms near centromere (45 not 46)

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33
Q

Inheritance patterns
- Imprinting

A

Gene expression depends on which parent the chromosome came from
- Maternal imprinting = maternal gene silenced (pat expressed)
- Paternal imprinting = paternal gene silencing (mat expressed)

Occurs during gametogenesis/embryonic development

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34
Q

Inheritance patterns
- Triplet repeat

A

Disease becomes more severe as generations go on
(greater expansions with each inheritance)

  • I.e Fragile X, Huntington, Myotonic dystrophy, spinocerebellar ataxia
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35
Q

Inheritance patterns
- Mitochondrial

A

Mum affected, passes on to both sexes

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36
Q

Inheritance patterns
- Mitochondrial

A

Mum affected, passes on to both sexes

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37
Q

Autosomal dominant with incomplete penetrance

A

Males and females
Can skip a generation but sometimes transmitted

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37
Q

Meier-Gorlin syndrome

A

ORC1 gene: short stature, microcephally, micrognathia, under-developed or absent patella and small ears.

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38
Q

Pierre Robin sequence

A
  • Micro/retrognathia, mandibular hypoplasia
  • Glossoptosis
  • Cleft palate WITHOUT cleft lip

Rx: prone positioning, NGT feeds/NPA, surgical distraction if severe

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39
Q

Miller Syndrome

A

Malar hypoplasia, micrognathia, cleft lip and cleft palate and downward slanting eyes

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39
Q

Duane Syndrome

A

Sporadic, some AD
Congenital strabismus
L) > R) eye

Type 1 = difficulty with abduction (one D in abduction)
Type 2 = difficulty with adduction (two Ds in adduction)
Type 3 = difficulty with both (3 Ds in abduction and adduction).
80% of cases are type 1

Associations: Klippel-Feil anomaly and hemifacial microsomia

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40
Q

Goldenhaar/Hemifacial microsomia

A

1 in 5,000
- Unilateral orbit, ear, facial muscle &mandible hypotrophy
- Microtia/hearing loss
- Epibulbar dermoids (eye)

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41
Q

Townes-Brocks

A

SALL1 gene TCOF1 gene
- Dysplastic ears
- Imperforate anus
- Malformed thumbs

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42
Q

Treacher-Collins

A

TCOF1 gene
- Midface hypoplasia
- Cleft palette
- Ear & eye abnormalities

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43
Q

Pendred syndrome

A

Iodine transport mediated by pendrin
= giotre + SNHL
- Usually no thyroid dysfunction, may have mild hypothyroidism

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44
Q

NF1

A

Autosomal dominant, 50% sporadic
Chr 17

> 6 cafe au lait
2 lisch nodules
axillary freckling
optic glioma
2 neurofibroma/1x plexiform neurofibroma
Osseous lesions

+ve FHX

45
Q

NF2

A

Autosomal dominant, 50% sporadic
Chr 22

Bilat acoustic neuroma
Meningiomas
Cataracts

+ve FHX

46
Q

Tuberous Sclerosis 1/2

A

Autosomal dominant, 75% sporadic

> 3 ash leaf spots
2 ungal fibromas
2 angiomyolipomas

Shagreen patch
Retinal harmatoma
Cardiac rhabdomyoma

Cortical dysplasia
Subependymal nodules/astrocytoma

Minor: Confetti skin lesions, dental pits, renal cysts, fibromas

47
Q

Diagnosis?

A

Williams
Autosomal dominant
7q11 del- ELN gene
‘Elfin facies’ with cocktail personality
Hypercalcemia
Supravalvular AORTIC/peripheral pulmonary stenosis (AS only if ELN point mutation)
Developmental delay/ID

48
Q

Diagnosis?

A

Alagille
Autosomal dominant
JAG1/NOTCH2
Short, triangular face
Butterfly vertebrae
Peripheral pulmonary stenosis

Ix: PAUCITY OF BILE DUCTS on Bx, conjugated hyperbilirubinemia
Prone to Moya Moya disease

49
Q
A

Marfan’s
Autosomal dominant- FBN Ch15
Arm span >height, tall, joint hypermobility
MVP/aortic aneurysms, ectopia lentis (upward), learning disability

50
Q

Ehlers Danlos

A

Autosomal dominant
COL5A
Tall, joint hypermobility
Easy bleeding, berry aneurysms, aortic root dilatation

51
Q

Diagnosis?

A

Osteogenesis imperfecta

Autosomal dominant COL 1A1/2

High ALP, hypercalciuria
Short stature
Blue sclera, opalescent teeth
Hearing loss and poor vision

Type 1- mild
Type 2- lethal
Type 3- progressive
Type 4- moderate

52
Q

Diagnosis?

A

Stickler Syndrome
Autosomal dominant- COL2A1

Cleft palete, PRS (hypoplasia mandible, glossoptosis)
MVP, joint hypermobility
SNHL

53
Q

Diagnosis?

A

Brachio-oto-renal syndrome
Autosomal dominant- EYA1
Pre-auricular pits/tags, microtia
SCM sinus/cyst
Renal malformations

54
Q

Diagnosis?

A

Diamond Blackfan Anaemia
Autosomal dominant

Triphalangeal thumb/absent thumb
Cataracts

Anaemia with low RCC, fatty BM
- Cx: AML

55
Q

Diagnosis?

A

Von Hippel Lindau Syndrome
Autosomal dominant- VHL Chr3
Multiple renal, liver, endocrine tumors

56
Q

Diagnosis?

A

Cornelia De Lange Syndrome
Autosomal dominant- NIBPL, SMC1A, most sporadic
Monobrow (synophyrys), hirstutism, short/upturned nose
ASD/VSD
ID

57
Q

Diagnosis?

A

Waardenburg Syndrome
Autosomal dominant

Pale blue eyes, white forelock
SNHL/vision loss

58
Q

Diagnosis?

A

Costello Syndrome
Autosomal dominant- RASMAPK/HRAS

Big babies, loose skin on hands, deep palmar crease
FTT
Rhabdomyosarcoma/neuroblastoma

59
Q

Diagnosis?

A

Noonan Syndrome
AD- RASMAPK/ PTPN11/SOS1, sporadic
Widely spaced nipples/sternal anomaly
Pulmonary stenosis (supravalvular), ASD, HOCM

Associated malignancies- JMML

60
Q

Diagnosis?

A

Cardiofasciocutaneous syndrome
Autosomal dominant- RASMAPK KRAS (similar to noonans)

Sparse curly hair, ID/dev delay
Seizures
HOCM

61
Q

Diagnosis?

A

Treacher-Collins Syndrome
Autosomal dominant
- Midface hypoplasia
- Microtia/SNHL
- Cleft

62
Q

A1AT Deficiency

A

Autosomal dominant
Defective A1AT builds up in lung
- Neonatal jaundice, pale stools & hepatomegaly- cirrhosis/renal failure (first 1-2yrs)
- Emphysema (panacinar/LL), chronic bronchiectasis- damage due to neutrophil elastase

Heterozygote: PiMZ = 60% function
Homozygote: PiZZ = 10-20% function- less likely to have liver disease

Biopsy: PAS+ve/diastase resistant

63
Q

Achondroplasia

A

Autosomal dominant
FGFR3, most sporadic
Inhibits chondrocyte development
Rhizomelic dwarfism
OSA/AA instability

64
Q

Diagnosis?

A

Apert
Autosomal dominant/sporadic
Craniosynostosis, exopthalmos, cleft palette, syndactyly
Mod ID

65
Q

Diagnosis?

A

Crouzon
Autosomal dominant
Craniosynostosis, hydrocephalus, proptosis, strabismus
Normal intelligence, normal hands & feet

66
Q

Diagnosis?

A

ADPKD
Autosomal dominant- Chr 4
Bilateral, large cystic kidneys
Multiple cysts throughout abdomen
Haematuria

67
Q

Familial Adenomatous Polyposis

A

Autosomal dominant
Multiple colonic polyps
+ve FHx- suggest yearly scope from 10y

68
Q

Li Fraumeni

A

Autosomal dominant
Multiple malignancies
- Sarcoma
- Breast cancer
- Adrenal Ca
- Leukemia

69
Q

MEN1, MEN 2A & B

A

Autosomal dominant

70
Q

Charcot-Marie-Tooth

A

Autosomal dominant
PMP2 (60%)- demyelinating, MFN2 (30%)- axonal

Peripheral neuropathy, foot drop
Motor > sensory
Normal CK
‘Onion bulb’ appearence on nerve Bx

71
Q

CHARGE

A

Autosomal dominant

Coloboma
Heart defects- tetralogy of Fallot
Atresia
Retardation (mental)
Genital abnormalities

72
Q

Diagnosis?

A

Hypomelanosis of Ito
Autosomal dominant
- Associated with seizures & developmental/cognitive delay

73
Q

Diagnosis?

A

Osler-Weber-Rendu (HHT)
Autosomal dominant

Skin lesions- cherry angiomas
GI bleeding/epistaxis/haematuria
AVMs

74
Q

Gilbert

A

Autosomal dominant
- Glucoronyltransferase
- Unconjugated hyperbilirubinemia
- Intermittent jaundice

75
Q

Diagnosis?

A

Peutz-Jeghers
Autosomal dominant

Risk of intestinal polyps & malignant transformation

76
Q

Myotonic dystrophy

A

Autosomal dominant
MD1 = DMPK
- GTG triplet repeat
- Anticipation- maternal

Myotonia (unable to relax muscles after action)
Muscle wasting
Cataracts
Cognitive delay

77
Q

Huntingtons

A

Autosomal dominant
- CAG triplet repeat
- Anticipation-paternal

Depression, choreiform movements/hemiballismus, caudate atrophy

78
Q

Diagnosis?
Types?

A

CF
Autosomal recessive

Type 1- no protein G,W,R
Type 2- cant fold (delF508)- F,N,I most common, Rx Lumicaftor
Type 3- cant transport G551D - G,S,V - Rx Ivacaftor
Type 4- decreased function- R117H, asymptomatic

79
Q

Dx?

A

Wilson disease
Autosomal recessive - ATP7B
<10y Liver/abdo Sx
>10y Abnormal movements/psychiatric disease

80
Q

Fanconi Anaemia

A

Autosomal recessive
FANCA/B

BM failure
Abnormal thumbs/radial aplasia
Short stature
Cafe au lait macules/ash leaf spots
CHD- PDA, ASD/VSD, situs inversus

Ix: high HbH, AFP, pos chromosomal breakage study

81
Q

Homocysteinuria

A

Autosomal recessive
Like Marfans but
Low IQ
Downward ectopia lentis
Coagulopathic

82
Q

Dx?

A

ARPKD
Autosomal recessive

Bilateral smaller cysts in kidneys
Potter’s sequence= oligohydramnios
- DDH/talipes
- Pulmonary hypoplasia
Flank mass, renal & liver dysfunction

83
Q

Bartter/Gitelman

A

Autosomal recessive
Bartter: N/K/Cl cotransporter DLH (frusemide)
- Hypokalemic/chloremic acidosis
- Stones
- Low Na/K+/Cl
- High urine Ca

Gitelman: Na/K transport DCT (thiazide)
- Low Mg2+, muscle cramps, polyuria
- Low K+, acid, high glucose/uric acid
- Low urine Ca

84
Q

Glanzman Thrombasthenia

A

Autosomal recessive
Normal platelet number
Gp2b1a defective
Unable to aggregate

85
Q

Dx?

A

Smith-Lemli-Opitz
Autosomal recessive
- Cholesterol synthesis problem
- Poor growth
- Cleft palete
- Cataracts
- ID
- Absent corpus callosum

86
Q

Cartillage-Hair-Hypoplasia

A

Autosomal recessive
- Dwarfism
- Sparse hair
- BM failure & increased risk of malignancy

87
Q

Carpenter

A

Autosomal recessive
- Craniosynostosis
- Fusion of fingers
- Situs inversus
- SNHL

88
Q

Ataxia-Telangectasia

A

Autosomal recessive
- Ataxia/nystagmus
- Telangectasia
- Recurrent sinopulmonary infections

Ix: high AFP, low IgA, lack of ATM protein on Western blot

89
Q

Metachromatic Leukodystrophy

A

Autosomal recessive
Hypotonia, distal weakness, absent reflexes

90
Q

SMA

A

Autosomal recessive
- Lack SMN1 protein
- Anterior horn - LMN signs, areflexia, decreased tone, fasciculation

Type 1 = most severe, never sit
Type 2 = intermediate, never stand
Type 3 = shoulder girdle

Normal CK
Bx: large gap atrophy

91
Q

Tay-Sachs

A

Autosomal recessive
Sphingolipid accumulation
Cherry red spots in macula

92
Q

TAR (thrombocytopenia absent radii)

A

Autosomal recessive

93
Q

Freidrich’s ataxia

A

Autosomal recessive
- Ataxia, weakness- distal
- Vision/speech/hearing changes
- HOCM
- high plantar arches

94
Q

Crigler Najjar

A

Autosomal recessive

Type 1 = severe lifelong jaundice rx transplant
Type 2 = less severe

95
Q

Kartageners/PKD

A

Autosomal recessive

Bronchiectasis
Infertility
Situs inversus

96
Q

Gluc-galactose malabsorption

A

Autosomal recessive
- Severe osmotic diarrhoea, improves when milk stopped
- Renal calculi
Ix: hydrogen breath test
Rx: fructose only formula/sugar

97
Q

Congenital chloride diarrhoea

A

Autosomal recessive
Dehydration
Low Cl/stool Cl high ++

98
Q

PKU

A

Autosomal recessive

Pale hair, blue eyes, eczema, pale skin
ID, seizures
Musty odour to urine
Rx: Low Phe diet

99
Q

Types of ciliopathies & features.

A

Joubert’s ( JBTS )
- AR
- Retinitis piigmentosa, ataxia, sleep apnoea/hyperpnea, polydactyly
- Absent corpus callosum

Dent’s- CLCN5 (1), ORCL1 (2)
- X-linked,
- Proximal RTA & stones
- Hypophosphatemic ricketts

Bardet-Biedl (BBS)
- Pleotropic
- Rod-cone blindness, polydactyly, obesity,LD

Meckel Gruber (MKS1/2)
- Encephalocoele, dysplastic kidneys, polydactyly

Senior Loken (NPHP)/Nephronopthisis
- SL: Juvelile NP/ progressive eye disease
- NP: polyuria/polydipsia, ESRF, CM cysts

McKusick Kaufman (MKS1)
- AD
- Hydrometrocolpos, hypospadias, ureteric atresia

Ellis-Van Creveld (EVC)
- Polydactyly, dwarfism, CHD/ASD, natal teeth, cleft

Leber congenital amaurosis
- Vision loss

PCD/Kartageners
PCKD

100
Q

Usher syndrome=

A

hearing loss, ataxia and retinitis pigmentosa

101
Q

Lowe Syndrome- Sx/gene

A

Oculocerebrorenal syndrome
OCRL1 gene- X linked
Bilateral cataracts from birth
Proteinuria/stones
Behavioral change/hypotonia

102
Q

Kearns Sayre Syndrome (what syndrome can precede?)

A

Mitochondrial myopathy with proximal weakness
Retinal degeneration
Conduction block
Ataxia

Ragged red fibres on Bx

Preceded by Pearson’s Syndrome: sideroblastic anaemia, pancreatic insufficiency & LBW

103
Q

Sx Lambert Eaton Syndrome

A
104
Q

Genetic conditions associated with coloboma?

A

*Aicardi syndrome
*Basal cell nevus (carcinoma) syndrome
*Cat-eye syndrome
*CHARGE
*Kabuki syndrome
*Linear sebaceous nevus syndrome
*Meckel-Gruber syndrome
*Rubinstein Taybi syndrome
*Trisomy13,18
*WalkerWarburg syndrome

105
Q

Examples of conditions due to haploinsufficiency?

A

Haploinsufficiency: reduction of 50% of gene function results in an abnormal phenotype

Williams syndrome
CHARGE syndrome
Cleidocranial dysostosis
EDS
Marfan syndrome
Holt-Oram

106
Q

Which conditions display the dominant-negative effect?

A

Definition = altered gene product that acts antagonistically to the wild type

Cancer – p53, ATM
Marfan syndrome

107
Q

Russel Silver, BWS, Prader Wili & Angelman genetics

A

Chromasome 7/11p
Russel-Silver syndrome
- Maternal UDP 7 (7%)
- Imprinting defects on 11p (30%)
- Structural chromosomal aberrations (1%)

Beckwith WiedeMANN
- Imprinting defects on 11p (60%)
- Paternal UDP 11p (20%)
- Gene mutation (CDKN1C) (10%)
- Paternal duplication, inversion, translocation (1-2%)

Chromosome 15
AngelMAN
- Microdeletion (70%)
- Paternal UDP 15 (1-3%)
- UBE3A mutation (5-10%)
- Imprinting defect (3-5%)

Prada-Willi syndrome
- Microdeletion (70%)
- Maternal UDP 15 (25%)
- Imprinting defect (3%)

108
Q

Russel Silver, BWS, Prader Wili & Angelman symptoms

A

Russel Silver
- Hemihypertrophy (small)
- Triangular face
- Decreased bone age

BWS
- Overgrowth
- Macroglossia
- Ear pits/tags
- Abdominal wall defects, risk embryonal tumors
- Hypoglycemia, obesity

Prader Wili
- Hypotonia/hyperglycemia
- Feeding difficulties
- ID
- Hypogonadism

Angelman
- Severe ID
- Inappropriate laughter
- Ataxia/seizures

109
Q

MRI findings in Jouberts (cerebello-oculo-renal syndrome)?

A

Molar tooth sign (cerebellar vermis hypoplasia)
- 25% will have nephronophthisis or renal dysplasia

110
Q

Define cascade testing in genetics?

A
  • Cascade testing involves determining whether or not it is present in other family members beyond the parents.
111
Q

Define segregation in genetics?

A
  • Segregation is the process of determining whether a variant of interest found in a patient is present in parents.

FRACP 2023 Cram Homicrons Edition (29 decks)

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