Paeds: Common chromosomal disorders Flashcards
Klinefelters syndrome: Affects
1/600-1/800 boys
Klinefelters syndrome: Majority caused by
Non-disjunction during maternal oogenesis
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.
Klinefelters syndrome: Diagnosis by
• Chromosome analysis
Many boys remain undiagnosed throughout childhood, with the diagnosis only coming to light during investigation of infertility.
Patau Syndrome (trisomy 13)
Incidence
1/6000 births
Patau Syndrome (trisomy 13) Causes
75% caused by non-disjunction during maternal oogenesis
20% Robertsonian translocation
5% result from mosaicism
Patau Syndrome (trisomy 13) Diagnosis
Trisomy 13 is usually diagnosed by antenatal US scan, since the majority of affected babies have multiple congenital anomalies
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
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.
Edwards Syndrome (trisomy 18) Incidence
1/8000 births
Femal excess
Edwards Syndrome (trisomy 18) Majority caused by
Non-disjunction during materanal oorgenesis
Edwards Syndrome (trisomy 18) Presentation
Presentation
Edwards Syndrome (trisomy 18) Other common features
Congenital heart disease usually VSD ± valve dysplasia
Short sternum
Overriding fingers
‘rocker-bottom feet’
Edwards Syndrome (trisomy 18) Median life expectancy
4 days, although some affected babies life for several months
Edwards Syndrome (trisomy 18) Diagnosis
Initial rapid interphase FISH testing followed by formal chromosome analysis (additional chromosome 18)
Genetic disorders with cardiac features
Digeorge syndrome
Marfans syndromes
Noonans syndrome
Williams syndrome
Genetic testing in cognitive impairment
Angelman syndrome (AS) Fragile X syndrome (FRAXA) Prader-Willi syndrome Rett syndrome Smith-Magenis syndrome Wiliams syndrome
Genetic disorders with neuromuscular features
Congenital myotonic dystrophy
Duchenne muscular dystrophy
Spinal musculal atrophy
Genetic disorders with dermatological features
Ehlers-Danlos syndrome
Neurofibromatosis type §
X-linked hypohidrotic ectodermal dysplasia
Tuberous sclerosis
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
Turners Syndrome Affects
1/2500 females
Turners Syndrome Genetic
Single X chromosome (45,X), usually due to non-disjunction
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
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)
Ehlers-Danlos Syndrome Incidence
1/5000 births
Ehlers-Danlos Syndrome Inheritance
Autosomal dominant
Ehlers-Danlos Syndrome All forms of Ehlers danlos are characterised by
Skin fragility
Unsightly bruising and scarring
Musculoskeletal discomfort
Susceptibility to osteoarthritis
Angelmann Syndrome Incidence
1/40,000
Angelmann Syndrome Caused by
Impaired or absent function of the maternally imprinted UBE3A gene on chromosome 15q11.13.
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
Fragile X syndrome
Incidence
1/5500 males
Fragile X syndrome Description
Commonest cause of mental retardation
Fragile X syndrome Caused by
A full expansion (>200 repeats) in the (CGG) triplet repeat in the FRAXA gene on chromosome Xq27.3
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
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
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
