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Flashcards in Paeds: Common chromosomal disorders Deck (36):
1

Klinefelters syndrome: Affects

1/600-1/800 boys

2

Klinefelters syndrome: Majority caused by

Non-disjunction during maternal oogenesis

3

Klinefelters syndrome: Boys with Klinefelters syndrome

• Enter puberty normally, but by mid-puberty the testes begin to involute and the boys develop hypergonadotrophic hypogonadism with decreased testosterone production (often tall and may develop feminine body build).
• Testes are small in adult life and men with Klinefelter syndrome are generally infertile (azoospermia).
• Gynaecomastia develops at puberty in >50%
Boys with Klinefelter syndrome typically have an IQ ~15 points lower than their siblings.

4

Klinefelters syndrome: Diagnosis by

• Chromosome analysis
Many boys remain undiagnosed throughout childhood, with the diagnosis only coming to light during investigation of infertility.

5

Patau Syndrome (trisomy 13)

Incidence

1/6000 births

6

Patau Syndrome (trisomy 13) Causes

75% caused by non-disjunction during maternal oogenesis
20% Robertsonian translocation
5% result from mosaicism

7

Patau Syndrome (trisomy 13) Diagnosis

Trisomy 13 is usually diagnosed by antenatal US scan, since the majority of affected babies have multiple congenital anomalies

8

Patau Syndrome (trisomy 13) Typical malformation sinclude

Holoprosecncephaly
SGA
Microcephalic
Micophthalmia
Cleft lip/palate
Congenital heart disease e.g. ASD or VSD
Renal anomalies e.g. fused kidneys
Postaxial polydactyly
Together with severe/profound mental retardation

9

Patau Syndrome (trisomy 13)Diagnosis is confirmed by

A chromosome analysis (additional chromosome 13)
Most cytogenetics laboratories are able to offer a rapid analysis e.g. interphase FISH, to confirm the diagnosis quickly.

10

Edwards Syndrome (trisomy 18) Incidence

1/8000 births
Femal excess

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Edwards Syndrome (trisomy 18) Majority caused by

Non-disjunction during materanal oorgenesis

12

Edwards Syndrome (trisomy 18) Presentation

Presentation

13

Edwards Syndrome (trisomy 18) Other common features

Congenital heart disease usually VSD ± valve dysplasia
Short sternum
Overriding fingers
‘rocker-bottom feet’

14

Edwards Syndrome (trisomy 18) Median life expectancy

4 days, although some affected babies life for several months

15

Edwards Syndrome (trisomy 18) Diagnosis

Initial rapid interphase FISH testing followed by formal chromosome analysis (additional chromosome 18)

16

Genetic disorders with cardiac features

Digeorge syndrome
Marfans syndromes
Noonans syndrome
Williams syndrome

17

Genetic testing in cognitive impairment

Angelman syndrome (AS)
Fragile X syndrome (FRAXA)
Prader-Willi syndrome
Rett syndrome
Smith-Magenis syndrome
Wiliams syndrome

18

Genetic disorders with neuromuscular features

Congenital myotonic dystrophy
Duchenne muscular dystrophy
Spinal musculal atrophy

19

Genetic disorders with dermatological features

Ehlers-Danlos syndrome
Neurofibromatosis type §
X-linked hypohidrotic ectodermal dysplasia
Tuberous sclerosis

20

Genetic disorders of growth

IUGR
- Silver-Russle syndrome
- Cornelia de lange syndrome
Short stature Turners syndrome
Tall stature marfans
Obesity
- Bardet-biedly syndrome
- Prada-willi syndrome
Overgrowth
- Beckwith-widemann syndrome
Sotos syndrome

21

Turners Syndrome Affects

1/2500 females

22

Turners Syndrome Genetic

Single X chromosome (45,X), usually due to non-disjunction

23

Turners Syndrome Presentation

Short Stature
Typical phenotype:
- Broad neck
- Ptosis
- Wide carrying angle at elbows (cubitas valgus)
- Widely spaced hypoplastic nipples
- Low posterior hairline
- Excessive pigmented naevi
Puffiness of the hands and feet is a common neonatal finding

24

Turners syndrome
Associated abnormalities include

Congenital heart disease (15-50%)
Especially coarctation of the aorta and VASD
Structural renal anomalies (~30%) e.g. horseshoe kidney or unilateral renal agenesis
Hypoplastic ‘streak’ ovaries (1o amenorrhoea and infertility)

25

Ehlers-Danlos Syndrome Incidence

1/5000 births

26

Ehlers-Danlos Syndrome Inheritance

Autosomal dominant

27

Ehlers-Danlos Syndrome All forms of Ehlers danlos are characterised by

Skin fragility
Unsightly bruising and scarring
Musculoskeletal discomfort
Susceptibility to osteoarthritis

28

Angelmann Syndrome Incidence

1/40,000

29

Angelmann Syndrome Caused by

Impaired or absent function of the maternally imprinted UBE3A gene on chromosome 15q11.13.

30

Angelmann Syndrome Presentation

A distinctive neurobehavioural condition with severe developmental delay
Profound speech impairement
An ataxic wide gait
Specific behavioural phenotype (excitable personality, hand-flapping and inappropriately happy affect
Seizures are common

31

Fragile X syndrome
Incidence

1/5500 males

32

Fragile X syndrome Description

Commonest cause of mental retardation

33

Fragile X syndrome Caused by

A full expansion (>200 repeats) in the (CGG) triplet repeat in the FRAXA gene on chromosome Xq27.3

34

Fragile X syndrome Boys with fragile X syndrome

Typically have global developmental delay often with gaze avoidance, sterotyped repetitive behaviours such as hand-flapping and resistance to change of routines

35

Fragile X syndrome Up to 50% of girls with a full FRAXA expansion will have

Learning and behavioural difficulties that are similar to, but less severe than those seen in affected boys

36

Fragile X syndrome Learning and behavioural difficulties that are similar to, but less severe than those seen in affected boys

Very complex and there will be genetic implications for relatives.
Referral to a clinical geneticist is recommended

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