Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FRACP Exam > Genetics > Flashcards

Genetics Flashcards

1
Q

Penetrance

(non-mendelian inheritance)

A

definition: % of people with the genotype exhibiting phenotype

incomplete penetrance: condition not detected in an individual with causative genotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Achondroplasia

A

defect: single gene mutation in FGFR3

  • AD, sporadic in 80%

genetic testing: single gene sequencing FGFR3

pathophysiology: normal FGFR3 has a negative regulatory effect on bone growth. mutation produces a constitutively active gene

incidence: 1/25,000

clinical:

  • facies: macrocephaly, frontal bossing, flat midface/nasal bridge
  • physical: short, rhizomelic limb shortening, trident hand, kyphosis, varus/valgus defomities, narrow spinal canal, OSA, middle ear disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Albright hereditary osteodystrophy

(Pseudohypoparathyroidism)

A

genetic: AD

pathogenesis: Gs alpha subunit deficiency

clinical: pseudohypothyroidism, short stature, short 4/5th metacarpal, round face, MR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Alagille syndrome

A

defect: AD single gene mutation in JAG-1 gene Ch20p12

  • 10% deletion, 50% point mutation

clinical:

  • facies: triangle face, deep set eyes, prominent jaw
  • physical: butterfly vertebrae 87%, posterior embrotoxon of eye (88%)
  • cardiac: PPS (85%)
  • GI: intrahepatic bile dysgenesis, chronic cholestasis (91%), deficiency fat soluble vitamins
  • renal: structural abnormality/function 40%

investigations:

  • serum: increased bilirubin/aminotransferases
  • liver biopsy: reduced number bile ducts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Angelmans syndrome

A

incidence: 1/45,000

defect: 11q11-13 gene for UBE3A expressing ubiquitin ligase

  • deletion maternal sequence (paternal copy imprinted)

genetic test: methylation testing 15q11.2-q13

clinical:

  • physical: 20-80% hypopigmented skin/eyes, swallowing issues, prominent mandible, wide mouth, drooling, smooth palms
  • cognitive: severe ID, DD, sleep disturbance, seizures, jerky movements, flapping, laughter/smiling, happy demeanour

investigations:

  • EEG: high amplitude delta activity with intermittent spike and slow-wave discharges
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Anticipation

A

definition: early onset, more severe or accelerated disease in successive generations

associations: triplet repeat disorders eg. MD, Huntington’s

pseudo-anticipation: caused by ascertainment bias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Apert syndrome

A

genetics: sporadic

clinical: coronal synostosis, maxillary hypoplasia, high palate, strabismus, syndacyly (mitted hands/feet)

  • 66% hydrocephalus and intellectual disability

*Like Crouzon but abnormal hands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Autosomal dominant

A
  • most gain of function
  • most new mutations
  • less severe
  • variable expressivity/penetrance
  • can skip generations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Autosomal Dominant

A
  • Achondroplasia
  • Alagille
  • CHARGE
  • Cornelia de Lange
  • Ehler Danlos
  • Marfan
  • Myotonic Dystrophy
  • NF1
  • Noonan
  • Stickler
  • Tuberous sclerosis complex
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Autosomal recessive

A
  • usually lose of function
  • associated consanguinity
  • common to skip generations
  • more severe
  • less variability in families
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Autosomal Recessive

A
  • Smith-Lemli-Opitz
  • Ataxia telangiectasia
  • Mucopolysaccharidoses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Bardet-Biedel syndrome

A

genetics: autosomal dominant

mechanism: unclear

clinical: obesity, retinitis pigmentosa, polydactyly, hypogonadism, and renal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Beckwith-Wiedemann Syndrome

A

incidence: 1:13,700

defect: range of defects with abnormal imprinting 11p15 causing overactive IGF-2 gene causing an overgrowth disorder

  • 85% sporadic, 15% inherited, associated IVF

genetic test: methylation studies 11p

symptoms:

  • facies: macroglossia, macrosomia, ear pits/creases
  • physical: hemihypertrophy, abdo wall defects (omphalocoele/hernia), visceromegally, naevus flammeus
  • endocrine: hypoglycaemia (hyperinsulinaemia)
  • renal abnormalities

associated cancers: Wilm’s tumour (5-10%), hepatoblastoma, rhabdomyosarcoma, NB

  • abdominal US every 3 months until 8 years
  • AFP every 3 months until 4 years
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Brachio-oto renal syndrome

A

genetics: rare AR

clinical: hypoplastic/absent kidneys, ear and neck abnormalities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CHARGE syndrome

A

incidence: 1/10,000

genetics:

  • mutations CHD7 chromosome 8 (60%)
  • association: non random anomalies that occur together more often than you would expect by change

clinical:

C- coloboma, CNS anomalies

H- heart defects

A- atresia of the choanae

R- retardation growth/development

G- GU defects

E- ear anomalies/deafness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Choroideraemia

A

incidence: rare

genetics: mutation in CHM gene X chromosome, males only

pathophysiology: degeneration of the choroid and retina

clinical: night blindness then progressive loss of vision

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Chromosome 11 disorders

A

Ataxia telangiectasia

  • ATM gene
  • AR
  • clinical: B/T cell defects, low Ig, ataxia, oculocutaneous telangiectasia, MR, FTT, DM, secondary cancers, raised AFP/CEA

Beckwith-Wiedemann

  • 11p15: abnormal methylation, uniparental disomy
  • sporadic
  • clinical: macrosomia, macroglossia, exomphalos, organomegally, hyperinsulinaemia, MR, ear creases/puts, hemihypertrophy, Wilm’s
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Chromosome 12 disorders

A

Noonan’s syndrome

  • PTPN 11 (protein tyrosine phosphatase)
  • AD
  • clinical: PS, septal defects, HCM, webbed/short neck, pectus excavatum, wide nipples, cubitus valgus, short, ptosis, low ears, small genitals, coag defects, MR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Chromosome 13 disorders

A

Retinoblastoma

  • RB1 gene, hereditary or somatic
  • AR 90% penetrance
  • clinical: retinoblastoma, 25% of cases bilateral (always hereditary), also increased risk osteogenic sarcoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Chromosome 15 disorders

A

Prader Willi

  • 15q deletion: 70% paternal deletion, 25% UPD maternal
  • clinical: severe hypotonia, obesity, short, small hands/feet, hypogonadism, MR

Angelmann’s

  • 15q deletion: most maternal deletion (lower UPD)
  • clinical: hypotonia, fair hair, midface hypoplasia, seizures, prognathism, ataxic movement, laughter, MR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Chromosome 17 disorders

A

Neurofibromatosis 1

  • neurofibromin protein (tumour suppressor)
  • 1/2 sporadic, AD
  • clinical: skin/eyes neurofibromas, bone, brain tumours, RAS, macrocephally

Charcot Marie Tooth

  • 17q11.2 gene producing myelin protein P22
  • AD
  • clinical: motor, sensory, autonomic neuropathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Chromosome 19 disorders

A

myotonic dystrophy

- CTG repeat

  • AD with anticipation
  • clinical: weakness, heart conduction defects, DM, cataracts, testicular failure, MR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Chromosome 20 disorders

A

Alagille syndrome

  • JAG1 gene: microdeletion 20p12
  • AD
  • clinical: peripheral PA stenosis, liver disease, decreased intrahepatic intralobular bile ducts, high cholesterol, butterfly vertebrae, short, FTT, high voice, deep eyes, broad forehead, hypertelorism, pointed chin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Chromosome 22 disorders

A

Di George

  • 22q11.2 delection
  • 95% sporadic, AD
  • clinical: CATCH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Chromosome 3 disorders

A

Von Hippel Lindau

  • AD
  • benign/malignant tumours: haemangioblastomas, RCC, retina, phaeochromocytoma, pacreatic, middle ear
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Chromosome 4 disorders

A

Achondroplasia

  • FGFR-3 gene: gain of negative function
  • AD: 80% new mutations
  • incidence: most common non lethal skeletal dysplasia
  • clinical: short limbs, low nasal bridge, coarse features, midface hypoplasia, caudal narrow SC, delayed motor milestones, OSA, trident hand
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Chromosome 5 disorders

A

Spinal muscular atrophy

  • SMN1 gene
  • AR carrier frequency 1/80
  • most common NMD after DMD
  • type 1 (infantile): frog leg, areflexia, tongue atrophy, fasciculations, swallowing/resp difficultires
  • type 2 (3m-15yrs): proximal weakness, decreased/absent reflexes, survival 30yrs
  • type 3 (5-15yrs): hip girdle weakness, calf hypertrophy, walk to 40s

Adenomatous polyposis coli

  • APC tumour suppressor gene 5q21
  • AD
  • clinical: polyposis 10yrs, 100% risk colorectal cancer, assoc duodenal ampullary/thyroid/hepatoblastoma/gastric/medulloblastoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Chromosome 7 disorders

A

Williams syndrome

  • deletion long arm (7q11) >25 genes for protein elastin
  • sporadic
  • clinical: supravalvular AS, peripheral PS, hypercalcaemia, serrated teeth, carp mouth, hypertelorism, small upturned nose, puffy eyes, chattery, stellate iris, MR, elfin facies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Chromosome 8 disorder

A

Hereditary spherocytosis

  • AD
  • deficiency of RBC membrane structural protein spectrin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Chromosome 9 disorders

A

Tuberous sclerosis

  • TSC1 protein encoding harmatin (complexes with tuberin): both tumour suppressor genes
  • 2/3 new mutations, 1/3 AD
  • clinical: brain (seizures, MR, tubers, tumours (eyes, heart, lung, skin, liver, muscle)

Fredrich’s ataxia

  • trinucleotide repeat of GAA encoding frataxin
  • deficiency of frataxin leads to Fe accummulation in mitochondria
  • AR
  • clinical (5-15yrs): dorsal columns (loss DTR/sensory changes), lateral CS tract (spasticity, upgoing plantars), spinocerebellar tracts (ataxia), cardiomyopathy, scoliosis, optic atrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Consanguinity

A

incidence: >8% globally

associations: congenital/genetic disorders x2

shared genes:

  • 1st degree: 1/2 genes
  • 2nd degree: 1/4 genes
  • 3rd degree: 1/8 genes (progeny homozygous at 1/16 loci, 6% chance severe abnormality)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Contiguous gene syndrome

A

cause: abnormality of 2 or more genes located next to each other

pathogenesis: microdeletions or microduplications of chromosome segments

examples:

  • DiGeorge 22q11
  • WAGR syndrome 13q14.11
  • PWS/Angelman syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Cornelia de Lange Syndrome

A

incidence: 1/10,000

defect: single gene mutation in cohesion complex

  • 60% gene NIPBL on chromosome 5, SMC1A, SMC3
  • most sporadic

genetic testing: single gene sequencing

clinical:

  • facies: short nose, long philtrum, synophrys (unibrow), arched eyebrows, long lashes, microcephaly
  • physical: hirsutism, ulnar-ray defect, GORD
  • IUGR, severe ID, obesity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Crouzon

A

assoc: advanced maternal age

clinical: tall flat forehead, proptosis, midface hypoplasis

  • like Alpert’s but normal hands
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

DNA

A

4 nucleobases

purines: Adenine (A), Guanine (G)

pyrimidines: Thymine (T), Cytosine (C)

A-T: 2 hydrogen bonds

C-G: 3 hydrogen bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

DNA>RNA>Protein

A

DNA to RNA (transcription) nucleus

  • RNA polymerase binds promoter sequence 3’ and unwinds the helix
  • DNA/RNA form H bond and DNA read 3’ to 5’
  • RNA strand formed 5’ to 3’
  • with bond breakage at terminator sequence

RNA to protein (translation) ER in cytoplasm

  • movement 3’ to 5’ through tRNA from anti-codon side to AA binding side
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Duchenne Muscular Dystrophy

A

incidence: 1/3500

genetics: X-linked recessive Xp21 gene, BOYS

pathophysiology:

  • mutation in gene dystrophin
  • excess Ca penetrates sarcolemma causing rupture, oxidative stress, cell death, necrosis

clinical:

  • onset symptoms age 2-3years
  • progressive proximal muscle weakness of legs/pelvis (Gower’s sugn)
  • spreads to arms/neck
  • early pseudohypertrophy, low endurance, difficulty standing/stairs
  • LATER: cardiomyopathy, dysaarhythmias, scoliosis, respiratory disorders

prognosis:

  • wheelchair dependent age 12
  • life expectancy 25

diagnosis:

  • CK, EMG, genetics, muscle biopsy

treatment: steroids, beta2agonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Ehler danlos syndrome

A

incidence: 1/20,000

genetics: most AD type-V collagen via gene COL5A1/COL5A2/COL1A1

  • also mutations in other fibrous proteins and enzymes

pathophysiology: altered structure, production, or processing of collagen/proteins

clinical:

  • msk: hyperflexible joints, thoracic outlet syndrome, tearing tendons/muscle, myalgia, scoliosis
  • skin: fragile, livedo reticularis
  • CVS: arterial rupture, MVP, dilated aorta, Raynaud’s, cardiac conduction disorders
  • hiatus hernia, GORD, anal prolapse
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Epigenetics

A

definition: how the DNA is read and manifested

gene regulation:

  • histone modification: alters DNA conformation/transcription
  • DNA methylation: can silence promotors
  • non coding RNA: mediate gene regulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Fanconi anaemia

A

incidence: 1/130,000, Ashkenazi Jews

defect: AR mutations in both copies of DNA repair genes (17 FA genes)

pathophysiology: defect in proteins responsible for DNA repair

clinical:

  • physical: congenital defects (75%), microcephaly, short, hypo/hyperpigmentation (CAL, freckles), radial ray abnormalities
  • organs: renal anomalies, GI atresia, BM failure (1st decade, pancytopaenia, 90%)
  • cognitive: DD
  • endocrine issues 75%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Fetal alcohol syndrome

A

clinical:

Face: short palpebral fissues, flat philtrum, thin upper lip

Abnormal learning: jittery infants, learning disability, DD, seizures

Short: IUGR, microcephaly, short stature

criteria for diagnosis:

  • all 3 facial abnormalities + growth deficit + CNS abnormality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

FISH

A

method: fluorescent probes to bind parts of chromosome

use: specific for chromosome or region

eg. Cri Du Chat

benefits: fast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Fragile X syndrome

A

defect: expansion of CGG trinucleotide repeat affecting the FMR1 gene on X chromosome

genetic test: size triplet repeat (PCR/southern blot)

pathophysiology: reduced function FMR protein

premutation allele: 55-200 repeats

  • late onset tremor/ataxia, learning difficulties, social anxiety
  • females 21% have early menopause

full mutation: >200 repeats

  • facies: long face, large ears, strabismus
  • physical: high palate, hyperextensible joints, flat feet, hypotonia, macroorchidism
  • cognitive: ID mild to severe, ADHD (most), >50% autism

* females with full mutation can have a full or milder phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Genetic causes miscarriage

A

parental karyotype: inversions, translocations

coagulopathies: antiphospholipid sx/thrombophilia

endocrine issues: DM, thyroid

gynae: PCOS, uterine abnormalities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Genetic variations

A

point mutation: need gene sequencing

insertions/deletions: one or more nucleotides

DNA sequence variation: affects single base

silent mutation: change in base with no change AA

nonsense mutation: substitution that changes codon for AA to stop codon

missense mutation: substitution changes codon for one AA to another AA

splice site mutation: region between intron/exon, alters normal pre mRNA splicing (intron retention)

regulatory polymorphism: substitution alters binding affinity of transcript related proteins and protein production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Genomic imprinting

A

definition: differential expression of genetic information depending on maternal or paternal inheritance

examples:

  • PWS/Angelman’s
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Goldenhar

(oculo-auriculo-vertebral dysplasia)

A

defect: sporadic cause unknown

pathophysiology: 1st/2nd branchial arch maldevelopment

clinical:

  • hemifacial microsomia
  • confuctive deafness
  • visual field defect
  • vertebral defects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Homocystinuria

A

defect: AR single gene mutation in CBS gene

pathophysiology: cystathione beta synthase deficiency

  • inability to convert homocysteine to cystathionine
  • homocysteine accumulates damaging, CT/muscles/CNS

test: plasma total homocysteine

clinical: tall, stiff, ID, ectopia lentis (downwards), myopia

treatment: methionine restricted diet, folate/B12 supplementation

complications: thrombi, CVA, seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Hunter syndrome

A

genetics: XLR (only one that only affects males)

incidence: RARE, 2000 worldwide

pathophysiology: mucopolycsaccharidosis II

  • lysosomal storage disease caused by deficient enzyme iduronate-2-sulfatase
  • accumulation of substrated heparan sulfate and dermatan sulfate

clinical: macrocephaly, DD, short, abnormal skeletal development, hepatosplenomegally, inguinal hernia, NO CORNEAL OPACITY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Huntington’s disease

A

genetics: Huntingtin gene (HTT) chromosome 4

  • encoding protein Huntingtin (HTT)
  • gene contains trinucleotide repeat (CAG) usually <36 copies
  • 36-39 reduced penetrance, 40+ full penetrance

inheritance: autosomal dominant

  • new expansions as CAG repeats 28+ are unstable
  • increases in repeat no. cause anticipation

clinical: onset 35 to 44 years

  • personality: anxiety, depression, blunted affect, aggression
  • cognition: executive function, memory
  • physical: chorea
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Hurler syndrome

A

definition: MPS-1 lysosomal storage disease (most severe)

genetics: AR

defect: genes encoding lysosomal enzymes needed to degrade glycosaminoglycans (GAG) (formerly iknown as mucopolysaccharides) causing accummulation in cells, blood, CT

clinical:severe, progressive mental/physical decline with death by 10 yrs

  • onset 6-24 mths with characteristic features
  • coarse facial features,large tongue, prominent forehead, short stature
  • corneal clouding, hearing loss
  • -* hepatosplenomegaly, cardiomyopathy
  • skeletal dysplasia: dysostosis multiplex, joint stiffness

diagnosis: radiographs, urinary GAG excretion, enzyme assays

treatment: BMT, enzyme replacement.

52
Q

Imprinting

A

definition: genetic phenomenon occurs in SOME chromosomes

method: genes marked as maternal/paternal origin

  • eg. DNA methylation (turns off), histone modifications
  • some genes behave differently if they’re from mother/father

imprinted chromosomes: 7, 11, 15

imprinting disorders: PWS, Angelman, BWS, RSS

methylation studies: look methylation profile maternal/paternal genes

53
Q

Jervell and Lange-Nielsen syndrome

A

genetics: AR

  • mutations in KCNE1 and KCNQ1 genes which form potassium channels

incidence: 1/1 million

clinical: bilateral SNHL, long QT

54
Q

Kabuki syndrome

A

incidence: 1/32,000

defect: AD loss of function mutation KMT2D chromosome 12

clinical:

  • facies: wide eyes, arched interrupted eyebrows, broad nose, cleft/high arched palate, large/low ears
  • physical: hearing loss, short stature, short fingers, loose joints
  • cognitive: ID
55
Q

Kallmann syndrome

A

incidence: 1:10,000 M>F

gene: chromosome X KAL1 gene

clinical:

  • GnRH deficiency/gonadotropin deficiency
  • failure of puberty
  • hypogonadism
  • disorders of olfaction
  • cleft palate
  • skeletal defects
  • renal issues
56
Q

Karyotype

A

method: direct visualisation chromosomes

use: large changes, translocations

57
Q

Key genetic terms

A

aneuploidy: abnormal no. of chromosomes within a cell

compound heterozygote: 2 mutations same gene leading AR phenotype

epigenetic change: alteration of phenotype w/o changing genotype

epistasis: gene/gene interaction producing different phenotype

euploidy: multiple of the monoploid no.

expressivity: variable phenotype individuals same genotype

linkage: tendency of genes close to be inherited together

polymorphism: genetic region more than one allele present >1% (mutation is

58
Q

47XXY

Klinefelter syndrome

A

incidence: 1:1,000

genetics: non dysjunction sex chromosomes in meiosis (47 XXY), 20% mosaicism

genetic test: karyotype, microarray

clinical:

  • physical: weak, tall, poor coordination, less hair, small genitals, breast growth
  • cognitive: low IQ, impulsive, poor attention/judgement/insight
  • fertility: primary gonadal failure (normal age onset of puberty but no secondary sexual changes), less interest in sex

investigations: high FSH/LH, low testosterone (testosterone may be normal to mid-puberty)

comorbidities: breast cancer

treatment: androgen treatment age 11-12, aromatase inhibitors for gynaecomastia

59
Q

LEOPARD syndrome

A

genetics: 2 genes PTPN11 and RAF1

clinical: Noonan syndrome with multiple lentigines

Lentigines: reddish/brown macules to skin (80%)

ECG abnormalities ie axis devations, hypertrophy, conduction defects, BBB

Ocular hypertelorism

Pulmonary stenosis

Abnormal genitals

Retarded growth

Deafness (SNHL)

60
Q

Lesch-Nyhan Disease

A

deficiency hypoxanthine-guanine phosphoribosyltransferase (enzyme brain)

HPRT gene

increased purine synthesis

X-linked

1:200,000

normal at birth but hypotonia, vomiting

hyperuricaemia, ID, dystonic movements, choreoathetosis, dysarthric speech, self-biting

MRI: reduced size basal ganglia

treat allopurinol, dental extraction

61
Q

Marfans syndrome

A

incidence: 1/5,000

genetics: AD single gene mutation of FBN1 on chromosome 15q21.1 encoding fibrillin-1 (glycoprotein in ECM)

  • 25% sporadic

clinical:

  • cardiac: aortic root disease (dilation, aortic regurg, dissection), MVP
  • eyes: ectopic lens (up and outwards) 80%, myopia
  • msk: tall/thin, hypermobile joints (Steinberg thumb sign/Walker-Murdoch wrist sign), decreased elbow extension, arachnodactyly, pectus deformity, scoliosis, decreased upper/lower ratio, ductal ectasia, hindfoot valgus
  • skin: striae

NORMAL IQ

ghent criteria positive if:

  • ARD + ectopia lentis
  • ARD + FBN1
  • ARD + systemic score >7

(in absence of FHx)

treatment: beta blockers/ARBs (slow aortic dilatation)

62
Q

McCune Albright Syndrome

A

genetics: somatic mutation ch 20

  • G protein mutation stimulated cAMP forming oncoprotein causing gland hyperfunction

DIAGNOSIS (2 of 3):

  1. Cafe au lait spots (Coast of Maine)
    - rarely cross midline
  2. Peripheral precocious puberty
  3. Polyostotic fibrous dysplasia

also: hypophosphatemic rickets, GH excess, Cushing’s thyrotoxicosis, arrhythmias, cholestasis

63
Q

McKusick-Kaufman syndrome

A

genetics: autosomal recessive, MKKS gene mutation

population: Amish

clinical: polydactyly, cardiac abnormalities, GU issues

  • similiar to Bardet-Biedel but no visual loss of MR
64
Q

Menke kinky hair disease

A

inheritance: X-linked recessive

gene: chromosome Xp13 ATP7A gene

defect: error copper transporting ATPase protein

clinical:

  • progressive neurodegeneration/severe MR
  • seizures, hypotonia, feeding difficulties, optic atrophy
  • colourless hair, kinky, fragile
  • chubby red cheeks
  • death <3yrs

investigations:

  • hair shaft: trichorrhexis nodosa, pili torti, monilethrix
  • serum: copper/caerulosplasmin low

management:

  • copper-histidine subcutaneously
65
Q

Microarray

A

method: molecular karyotype

  • patients blood and control blood is labelled and mixed together
  • spread across bored and discolouration if unbalanced expression of DNA region

use: 1st line investigation, detects deletion/duplications

negatives: will detect variance of unknown significant, will NOT detect balanced translocations/point mutations

66
Q

Microsatellite instability

A

definition: short segments of repetitive DNA bases scattered throughout genome in non-coding DNA

pathophysiology: propenisity to develop changes in no. of repeats due to DNA repair errors during replication

examples: colorectal, endometrial, ovarian and gastric cancers

67
Q

Mitochondrial inheritance

A

Mitochondria=Mother

  • sperm bring very little mitochondria to embryo
  • mito genome= mtDNA
  • mitochondrial DNA replicates autonomously with high mutation rate
  • ALL offspring mother affected
  • all eggs have different degrees of mutation
68
Q

Mitochondrial myopathy

A

genetics: maternal inheritance

pathophysiology:

  • ragged red changes to muscle

clinical: muscle weakness, neurological issues, hearing loss

69
Q

Mitosis

A

Mitosis: somatic cells

  • results in 2 diploid cells

Meiosis: germline cells

  • results in 4 sister gametes (haploid cells)
70
Q

Moebius syndrome

A

incidence: 2:1,000,000

pathogenesis: underdevelopment CN VI/VII caused by distruption of blood flow in prenatal development

characteristics:

  • facial paralysis
  • inability to move eyes vertically or close eyes
  • upper lip retraction
  • limb/chest wall anomalies
71
Q

Morquio syndrome

(MPS IV)

A

incidence: 1/200,000 most common MPS (type IV)

defect:

  • type I: deficient galactosamine-6-sulfatase
  • type II: deficient beta-galactosidase
    pathophysiology: excess GAGs cause organ damage

clinical:

  • macrocephaly
  • hypermobile joints
  • short stature
  • abnormal development bones: scoliosis, bell-shaped chest
  • coarse facies, wide spaced teeth
72
Q

Mosaicism

A

definition: occurence of cells that differ in their genetic component from other cells in the body

germline: affecting ova/sperm

somatic: affecting cells other than germline

mixed: germline/somatic

73
Q

Myotonia congenita

A

definition: neuromuscular channelopathy

genetics: CLCN1 gene

pathogenesis: CIC forms Cl- channel causing delayed relaxation of skeletal muscle fibers

clinical: prolonged muscle contractions mainly LL

  • worse with inactivity

types: Becker (later/more severe), Thomson

74
Q

Myotonic dystrophy

A

genetics: trinucleotide repeat disorder

DM1: DMPK gene chromosome 19 CTG repeat

DM2: ZNF9 gene on chromosome 3 CCTG repeat

inheritance: autosomal dominant

clinical:

DM1: severe congenital + milder childhood forms

  • facial muscles, distal muscles forearm, respiratory failure and death

DM2: severe congenital + adult

  • rarer, proximal myotonic myopathy
75
Q

Neurofibromatosis 2

A

incidence: 1/25,000

defect: NF2 gene on Ch22q1.11

diagnosis with 1 of 4:

  1. Bilateral vestibular schwannomas
  2. 1st degree relative NF2 + uni vestibular schwannoma

OR any 2 other tumours (meningioma, schwannoma, glioma, neurofibroma, posterior subscapular lenticular opacities)

  1. Uni vestibular schwannomas + 2 other tumours
  2. Multiple meningiomas and uni vestibular schwannoma OR 2 other tumours

diagnosis: clinical

prognosis: 40% medical problem, 50% learning problem, 6% ID, 5% morbidity

76
Q

Neurofibromatosis type 1

A

definition: tumour disorder

incidence: 1/100,000, no assoc sex/race

defect: AD mutation NF1 gene on chomosome 17 encoding neurofibromin

  • 1/3 are new mutations
  • 100% penetrance by 5 years

diagnosis (at least 2 of the following):

1. >5 CAL macules

  • >5 mm in diameter prepubertal/>15 mm postpubertal
  • 100% NF1 have CAL

2. >1 neurofibroma or 1 plexiform neurofibroma

3. freckling axillary/inguinal regions

  • 80% by 6 yrs

4. >1 Lisch nodule

  • 40% by 4 years, 100% adults

5. optic glioma (low grade astrocytoma)

6. distinctive bony lesion

  • sphenoid dysplasia, thickening of long bone cortex, pseudoarthrosis

7. 1st degree relative with NF1

associations: macrocephaly, learning difficulties 30%, seizures 8%, scoliosis 10%, HTN, malignant malformations 3%, aqueductal stenosis, precocious puberty

investigations:

MRI: unidentified bright objects (disappear by 30 yrs)

77
Q

Noonans syndrome

A

incidence: 1/1000, both sexes

defect: AD, 60% mutation PTPN1 chromosome 12q24.1 encoding tyrosine phosphatase SHP-2

gene testing: single gene sequencing, of PTPN11 and 11 other Noonan genes

clinical:

  • cardiac: PS, LVH, HOCM 20%
  • neuro: ID, DD
  • haem: bleeding disorders, small risk leukaemia
  • physical: downslanting palpebral fissures, hypertelorism, low set ears, webbed neck, chest wall deformity
  • gonads: delayed puberty, cryptorchidism

diagnosis:

  • ECG: LAD and dominant S wave over precordial leads
78
Q

Northern blotting (RNA)

A

method: Southern blot but RNA instead of DNA

use: to determine size of mRNA/total RNA fragment produced by specific gene

79
Q

Osteogenesis imperfecta

(brittle bone disease)

A

incidence: 1/20,000

defect: mutations COL1A1 (most) and COL1A2 encoding type 1 collagen

  • most AD

genetic testing: OI gene panel or sequencing

pathophysiology:

  • type I: insufficient quantity collagen, mild disease
  • type II: insuffiency quality/quantity, severe/lethal perinatal period
  • type III: collagen defective, progressive deformity
  • type IV: decrease quality/quantity, deformed mesh like bones

clinical:

  • physical: short, blue sclerae, hearing loss, fractures
  • neuro: communication hydrocephalus, basilar invagination, seizures

treatment: bisphosphonate

80
Q

PCR

A

mechanism: amplify DNA fragment between two primers

method: select DNA, increase temp to separate strands, add primer, add polymerase

use:

  • selective DNA isolation eg. ecoli, paternity
  • amplification/quantification DNA to analyse small amounts DNA eg. ancient DNA
  • disease diagnosis eg. infections, cancer
81
Q

Pendred syndrome

A

genetics: AR, SLC26A4 gene encoding pendrin protein chromosome 7

pathophysiology: SLC26A4 in the cochlea, thyroid, kidney and participate in the excretion of bicarbonate

clinical: congenital SNHL, goitre 75% (euthyroid/hypothyroid)

82
Q

Peutz-Jegher syndrome

A

incidence: 1/25,000

genetics: AD STK11 gene

clinical:

  • hyperpigmented macules to lips/oral mucosa (melanosis)
  • GI hamartomatous polyps
  • bowel obstruction due to intussusception age 6-18yrs
  • 70% cancer: colorectal, stomach, small bowel, pancreas

management:

  • bowel radiography every 2 yrs
  • colonoscopy every 2 years
  • CT/MRI pancreas yearly
83
Q

Pfeiffer syndrome

A

clinical: midface hypoplasia, broad thumbs, variable syndactyly, proptosis

types:

  • type 1: mildest, normal IQ
  • type 2: clover leaf skull, severe proptosis
  • type 3: as for 2 without clover head
84
Q

Pierre Robin Sequence

A

NOT A SYNDROME

pathogenesis: underdevelopmet of jaw causes abnormal placement of tongue causing cleft palate and resp obstruction

clinical: micrognathia, airway obstruction, CP

association: Stickler syndrome is the commonest associated syndrome

  • cleft palate, bifid uvula, ocular defects, HF hearing loss, muskuloskeletal issues (scoliosis, femoral head failure, OA)
85
Q

Pleiotropy

A

definition: multiple phenotypes caused by single mutation

86
Q

Polygenic inheritence

A

definition: disease results from combination of multiple genes

examples: most non pathological eg. eye colour, height

different sex threshold: risk of disease different between sex

eg. if mother CAD higher risk in children than father, if mother pyloric stenosis then lower risk

87
Q

Prader Willi Syndrome

A

incidence: 1:10,000

defect: 15q11-q13 encoding SNRPN/necdin genes

  • deletion paternal sequence (20% uniparental) (maternal copy imprinted)
  • 99% sporadic

genetic test: methylation testing 15q

clinical:

  • triad H2O: hypotonia, hyperphagia, obesity
  • facies: almond eyes, strabismus, thin upper lip
  • physical acromicria (small hands/feet), obesity, insatiable appetite (high ghrelin), hypogonadism, undescended testes, hypopigmentation
  • cognitive: developmental delay, mild ID, psych issues

treatment: GH injections

88
Q

Prenatal diagnosis

A

CVS: from 11 weeks, placenta sampling, MS 1/100

Amnio: from 15 wks, amniotic fluid, MC 1/200

PGD: DNA extraction embryo and mutation detection testing

Non-invasive prenatal testing: FISH for common variations

89
Q

Proteus syndrome

A

genetic: very rare, unknown mutation

clinical: overgrowth skin, bones, muscle, fatty tissues, blood, lymphatics

  • tumours of skin, bone, ovaries, testical, meningioma, parotid glands as they age
90
Q

Refsum disease

A

genetics: AR

pathophysiology: peroxisomal disorder with impaired alpha oxidation of branched chain FAs resulting in buildup of phytanic acid in tissues

  • caused by PHYH mutations

clinical: onset in childhood/adolescence

  • neurological damage: cerebellar dysfunction, PN
91
Q

Repeat disorders

A

big repeats: worse from mother (eg. MD)

small repeats: worse from father (HD)

characteristics: unstable between generations, assoc anticipation, repeat size doesn’t accurately predict phenotype

triplet repeat disorders: Frederich ataxia, MD, Fragile X, HD

92
Q

Retinitis Pigmentosa

A

etiology: syndromic or non-syndromic (1/4000)

genetics: most inheretic forms of retinal degeneration

  • multiple genes and inheritance

syndromes: Usher (deafness), Kearns-Sayre (opthalmoplegia, dysphagia, ataxia), abetalipoproteinaemia (retardation, PN, ataxia, stearorrhoea), Bardet Biedel (DD, hypogonadism)

pathophysiology: progressive degeneration of the rod photoreceptor in the retina

clinical: onset infancy to adulthood

  • tunnel vision eventually extending into central field, night blindness (nyctalopia), and accumulation of bone spicules in the fundus
93
Q

mRNA Structure

A

5’ upstream, 3’ downstream

Exons: sense portion (Essential)

Introns: non-sense portions that need to be removed pre-translation by slicing (Idiots)

Codons: 3 units in mRNA encode specific AAs

  • 3 stop/start codons, 61 AA codons (only 20 AAs)
94
Q

RNA- 3 types

A

mRNA (messenger): mirror image of DNA with uracil instead of thiamine

tRNA (transfer): brings AA back to ribosomes

rRNA (ribosomal): make up the ribosome with enzymes

95
Q

Rubenstein-Taybi syndrome

A

genetics: microdeletion syndrome in 16p13.3 encoding the CREBBP gene

clinical:

  • short, ID, short/broad thumbs, hairy, cryptoorchodism
  • facies: beaked nose, high palate, downward palpebral fissues, broad nasal bridge

*risk with anaesthesia

96
Q

Russel Silver syndrome

A

incidence: 1/50,000

defect: 11p methylation defect resulting in decrease IGF-2 production

genetic test: methylation testing 11p

clinical:

  • neonatal: SGA, feeding issues, hypoglycaemia, wide/late closing fontanelle, GORD
  • physical: macrocephaly, triangle face, cafe au laie spots, blue sclerae, clinodactyly, body asymmetry, precocious puberty, low subcutaneous fat
  • NORMAL IQ

treatment: growth hormone

97
Q

Sex expression

(non-mendelian inheritance)

A
  • some genes expressed only in 1 sex
    eg. male pattern baldness
98
Q

Sialidosis

A

genetic: AR, mutation in gene chromosome 10 encoding neuroaminidase

pathogenesis: deficiency of neuraminidase causing accumulation of oligosaccharides; storage in liver, BM, brain

clinical:

type I: presents 2nd decade with myoclonus and cherry red spots

type II: congenital/ infantile/ juvenile

  • congenital: hydrops, ascites, HSM, stippling epiphyses, periosteal cloaking, stillbirth
  • infantile: dysostosi multiplex, moderate MR, visceromegaly, corneal clouding, cherry red spot, seizures
  • juvenille: edema, ascites, skeletal dysplasia, cherry red spot, dysostosis multiplex, visceromegaly, MR, dysmorphism, corneal clouding, neurological impairment, cherry red spots
99
Q

Smith Lemli Optiz

A

defect: AR mutation in DHCR7 causing inborn error of cholesterol synthesis

clinical:

  • facies: low/rotated ears, cleft lip/palate
  • physical: cerebellar hypoplasia, agenesis CC, polydactyly hands/feet, short thumb, syndactyly 1/2 toes, ambiguous genitals
  • CHD, renal/pulmonary/eye abnormalities
100
Q

Sotos syndrome

aka cerebral giantism

A

defect: NSD1 gene mutation (95% sporadic)

clinical:

  • facies: high hairline, high bossed forehead, long face, pointed chin
  • physical: overgrowth prenatal/postnatal, advanced bone age, hypotonia, premature tooth eruption
  • cardiac: PDA, ASD
  • cognitive: mild-severe ID

investigations:

  • MRI: dilated ventricles, cortical atrophy, abnormal corpus callosum
101
Q

Southern blotting DNA

A

method: transfer of electrophoresis separated DNA fragments to a filter membrane and subsequent fragment detection by probe hybridization

use: linkage to a DNA polymorphism

Old method uncommon now

102
Q

Spinal Muscular Atrophy

A

genetics: AR, gene SMN1

clinical: wasting or proximal muscles and lung

  • progressive muscular wasting and mobility issues
103
Q

Stickler syndrome

A

genetics: AD, COL2A1 gene

pathophysiology: subtype of collagenopathy affecting type II and XI

clinical:

  • flattened facial appearance
  • ocular: high myopia, retinal detachment, glaucoma
  • hearing loss
  • joint problems: hypermobile, arthritis
104
Q

Tay-Sachs

A

definition: lysosomal enzyme disorder

incidence: AR, 1:25 carrier in Ashkenazi jews

pathophysiology: mutation in HEXA gene Ch15 encodes hexoaminidase A a lysosomal enzyme

clinical:

  • initially normal development
  • hypotonia by 4-6 months
  • rapid regression by age 1 with spasticity/paralysis/MR/seizures
  • progressive blindness/deafness
  • macrocephaly
  • death by 5 yrs

diagnosis: decreased B-hexosaminidase A activity

105
Q

Translocations

A

unbalanced: a trisomy with the extra chromosome attached to a difference chromosone

balanced: disomy but 1 of the chromosomes stuck to another chromosome (normal phenotype)

robertsonian translocation: balanced translocation between short arms (p)

  • chromosomes 13, 14, 15, 21, 22 have very short p arms that only code ribosomal RNA
  • short arms break away and attach another chromosome and long arms fuse
  • results in 45 instead of 46 chromosomes
  • risk of unbalanced translocation in an offspring

insertional translocation: integration of donor segment into another chromosome

reciprocal translocations: non-homologous chromosomes swap parts

inversions: 2 breaks with segment flipped

  • normal phenotype but can mave miscarriages
106
Q

Treacher-Collins

A

incidence: 1/50,000

defect: AD single gene disorder in TCOF1

clinical:

  • facies: mandibulofacial dysostosis, sloping eyes, lower eyelid coloboma, malar hypoplasia, microtia
  • conductive hearing loss
107
Q

Triplet repeat sequences

A

definition: repeated sequence expands in successive generations leadomg tp abnormal phenotypes

examples: myotonic dystrophy, huntington’s disease

108
Q

Trisomy 13

Patau syndrome

A

defect: 3 copies of chromosome 13

  • usually nondysjunction and rarely translocation

genetic test: karyotype, microarray, FISH

clinical: holoprosencephaly, cleft lip/palate, heart abnormalities, scalp defect, ID

prognosis: mean survival 10 days

  • 80% die by 3 months and 92% by 1 yr

NOT LETHAL BUT HIGH MORBIDITY/MORTALITY

109
Q

Trisomy 18

Edward’s syndrome

A

defect: 3 copies chromosome 18 mostly nondysjunction

genetic test: karyotype, microarray, FISH

clinical: IUGR, wizened appearance, prominent occiput, overlapping fingers, rockerbottom feet, multiple malformations

prognosis: FDIU, death in first year most common

  • mean survival 14 days
  • 80% die by 3 months, 92% by 1 year
110
Q

Trisomy 21

Down syndrome

A

defect: 3 copies chromosome 21

  • dysjunction (95%), translocation (4%), mosaic (1%)

genetic test: karyotype, microarray, FISH

clinical:

  • facies: upslanting palpebral fissures, epicanthal folds, flat nasal bridge, brachycephalic head, small mouth, large tongue
  • CHD (50%): TOF, AVSD, PDA
  • GI: duodenal atresia (12%), hirschsprungs (<1%)
  • hypothyroid: congenital (1%), lifetime (15%)
  • deafness (75%), visual problems (60%)
  • OSA (50-75%)

other: low IQ, AML, atlanto-axial instability, dementia, sandle gap

111
Q

Tuberous sclerosis

“Zits, Fits + Deficits”

A

incidence: 1/6,000

genetics: AD mutation TSC1/TSC2 encoding hamartin/tuberin that form tumour suppressor complex

  • 2/3 sporadic

clinical: CNS involvement is the hallmark

diagnosis: 2 major or 1 major and 2 minor criteria

(see table)

others: seizures (20% of infantile spasms), autism, behavioural issues, low IQ, increased malginancy (RCC, giant cell astrocytoma), lymphangiomyomatosis

112
Q

45XO

Turners Syndrome

A

incidence: 1:5,000 (only 8% live births)

genetics: 45, X (50% mosaic)

  • maternal X retained in 66% SHOX

clinical:

  • physical: short stature, shield chest, wide spaced nipples, wide carrying angle, high arched palate, hearing problems
  • eyes: amblyopia/strabismus/ptosis/hypertelorism
  • CHD (30%): bicuspid aortic valve 15%, coarctation of the aorta 10%, aortic dissection, HTN
  • renal anomalies (50%): kidney dysplasia (horseshoe, abnormal vasc supply, uteropelvic obstruction)
  • fertility: amenorrhoea (30% enter puberty spontaneously), gonadal failure (infertile), gonadoblastoma, osteoporosis
  • AI: hypothyroidism (30%), ceoliac (10%), IBD), insulin resistance

treatment: GH injections, hormone replacements age 12

prognosis: mortality x3 normal pop

113
Q

VACTERL

A

incidence: 1/40,000

  • associated maternal DM but usually sporadic

cause: unknown, not syndrome but association

clinical:

Vertebral defects: small hypoplastic vertebrae/hemivertebrae

Anal atresia 55%: atresia or imperforate anus

Cardiac defects 75%: VSD/ASD/TOF

Tracheooesophageal fistula 70%

Esophageal atresia

Renal 50%/Radial abnormalities

Limb defects 70%: hypoplastic thumb, polydactyly, syndactyly, radial aplasia

114
Q

22q11 deletions

A

incidence: 1/4000

gene: AD 22q11.2 deletion (most common microdeletion syndrome involving 3 megabases of DNA with 30 genes)

AKA: DiGeorge syndrome, velocardiofacial syndrome

genetic test: FISH, microarray

pathophysiology: abnormal development 3rd and 4th branchial arches

clinical:‘CATCH’

Cardiac 40%: conotruncal/aortic arch defects

  • interrupted AA, truncus arteriosus (34%), TOF, VSD

Abnormal facies: low set/rotated ears, hypertelorism, high nasal bridge, micrognathia, short upward palpebral fissues

Thymic aplasia: variable level of T cell dysfunction, only 1% SCID

Cleft palate 50%: full or submucosal cleft, NO LIP

Hypocalcaemia/hypoparathyroidism: abnormal PT gland formation

ALSO: seizures, psychosis (60%), autism (20%), renal anomalies, ID (30%), learning difficulties (70%), hearing loss, facies (tubulara nose, large ears, small mouth)

115
Q

Waardenburg Syndrome

A

incidence: 1/50,000

genetics: AD, sporadic, mutations in variable genes

variance: types I-V

characteristics:

  • deafness
  • pigmentation anomalies: heterchromia, poliosis, patches hypopigmenation
  • defects of structures from neural crest: telecanthus, cleft lip/palate, spinal defects, hirschsprung’s
116
Q

WAGR Syndrome

A

Wilm’s tumour

Aniridia

Genitourinary abnormalities

Retardation

117
Q

Western blot (protein)

A

method: protein from cell extract separated by gel electrophoresis, placed on membrane, washed with Ab to protein, then washed 2nd Ab with dye

use: obtain information about size/amount of mutant protein of particular disorders

118
Q

Williams syndrome

A

incidence: 1/20,000

defect: heterozygous microdeletion on 7 due to misalignment in meiosis

genetic test: microarray, FISH

clinical:

facial features: widely spaced teeth, long philtrum, flattened nasal bridge, stellate eyes, puffy eyes

physical: short stature, developmental delay

cardiac: supravalvular aortic stenosis

endocrine: hypercalcaemia, hypothyroidism

gastic: colic, diverticulitis

neuro: low IQ, very talkative, social disinhibition, attention problems

behavioural: noctural enuresis

119
Q

Wiskott-Aldrich Syndrome

A

incidence: rare X-linked WASp gene, 1:25000

clinical: eczema, thrombocytopaenia, immune deficiency, blood diarrhoea,

investigations: low IgM, normal IgE/IgA, high IgG

treatment: avoid NSAIDs, BMT

120
Q

X chromosome disorders

A

Rett syndrome

  • deletion methyl-CpG-binding protein 2 (MeCP2)
  • lethal to males inutero
  • female: normal development/HC then regression

Fragile X

  • CGG repeat in FMR-1 gene
  • males more severe
  • clinical: autism, MR, long face, protruding jaw, big ears

Menke Kinky Hair disease

  • copper transporting ATPase gene
  • defective copper absorption
  • clinical: neurodegeneration 1st months, seizures, rosy cheeks, kinky hair

Adrenoleucodystrophy

  • ABCD-1 gene: prevents transport VLCFA into peroxisomes
  • clinical: 4-8 yrs, learning difficulties, behaviour issues, neurological degeneration

Duchenne muscular dystrophy

  • Xp21 deletion: dystrophin gene (1% X chromosome)
  • 1/3 sporadic
  • clinical: boys, onset 18m, weakness, cardiomyopathy, resp muscle weakness, contractures, scoliosis, MR
121
Q

X-linked

A

Recessive

  • Fragile X
  • Haemophilia
  • DMD/BMD

Dominant

  • Incontinentia Pigmenti
122
Q

XYY syndrome

A

genetics: aneuploidy of sex chromosomes due to error in separation during anaphase II meiosis ie nondysjunction

clinical: increase growth velocity, increase height, normal sex development/fertility, 50% learning disability/speech + language delay

investigations: normal testosterone

123
Q

Zellweger syndrome

A

defect: AR defect in protein require for assembly of peroxisomes (PEX genes)

pathophysiology: reduced function peroxisomes and accumulation of VLCFAs normally degrades in peroxisomes

clinical: hypotonia, tall forehead, midface hypoplasia, hepatomegally, eye abnormalities, renal cysts

investigations: abnormal MRI, elevated VLCFAs

prognosis: fatal by 12 months

124
Q

Associations Retinitis Pigmentosa

A
  1. Usher syndrome: hearing then RP
  2. Bardet Biedel: polydactyly, obesity, renal, MR
  3. Nephronopthisis
125
Q

Leri-Weill dyschondrosteosis

A

clinical:

  • mesomelic shortening
  • curved radius/ulna (Madelung deformity)
  • short 4th MC
  • muscular hypertrophy

genetic: AD SHOX gene mutation

126
Q

Rett syndrome

A

genetics: 1:20,000, X linked dominant gene MeCP2

  • fatal in males

clinical: onset 5-48 months

  • decreased head growth
  • loss of purposeful hand skills and social interests
  • stereotyped hand movements
  • gait disorder
  • seizures
127
Q

Usher syndrome

A

incidence: 1/100,000

genetics: AR 11 genes

clinical: retinitis pigmentosa, SNHL

FRACP Exam (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions