Syndromes Flashcards
(39 cards)
What is down syndrome?
Trisomy 21, most common autosomal trisomy and most common genetic cause of severe learning difficulties.
Incidence in live-born infants is about 1 in 650 and increases with maternal age
Clinical features of down syndrome
- round face and flat nasal bridge
- upslanted palpebral fissures
- epicanthic folds
- pigmented spots in iris
- small mouth and protruding tongue
- small ears
- flat occiput and third fontanelle
- short neck
- single palmar crease
- incurved and short fifth finger
- wide sandal gap between 1st and 2nd toes
- hypotonia
Neonatal complications of down syndrome:
- congenital heart disease is present in 40%
- duodenal atresia
- Hirschsprung disease <1%
- learning difficulties - varies widely
Prognosis of down syndrome:
- over 85% of infants survive to 1 year
- at least 50% of affected individuals live longer than 50 years
What should children with down syndrome be screened for?
Hearing/vision impairments, hypothyroidism, coeliac disease, atlantoaxial instability
Cytogenics of down syndrome?
- meiotic nondisjunction - 94%
- translocation - 5%
- mosaicism - 1%
What is meiotic nondisjunction trisomy 21?
- error at meiosis
- the chromosome 21 pair fails to separate so one gamete has 2 cr21 and one has none
- fertilisation of gamete with 2 cr21 gives rise to zygote with trisomy 21
- parental chromosomes do not need to be examined
- risk increases with increased maternal age, but more common in younger mothers as larger proprotion
- can occur in spermatogenesis
What is translocation trisomy 21?
- when the extra chromosome 21 is joined onto another chromosome (usually 14 but can be 15,21,22 - Robertsonian)
- parental chromosome analysis is recommended
- risk of recurrence is 10-15% if the mother is translocation carrier
- risk of recurrence is 2.5% if father is carrier
- if parent carries the rare 21:21 translocation all offspring will have down syndrome
- if neither parent carries translocation (75%) the recurrence risk is <1%
What is mosaicism trisomy 21?
Some cells are normal and some have trisomy 21. Milder down syndrome
Diagnostic investigations for down syndrome?
- rtPCR/FISH analysis of blood
- antenatal screening tests measuring biochemical markers in blood samples and nuchal thickening on USS
- amniocentesis if increased risk identified
- non-invasive prenatal testing - maternal blood analysed, part of routine screening can opt out
Later medical problems in down syndrome:
- delayed motor milestones
- learning difficulties
- short stature
- increased susceptibility to infections
- hearing impairment from secretory otitis media (75%)
- visual impairment from cataracts (15%), squints, myopia (50%)
- increased risk of leukaemia and solid tumours (1%)
- acquired hip dislocation/atlantoaxial instaiblity
- obstructive sleep apnoea (50%-75%)
- increased risk of hypothyroidism (15%) and coeliac disease
- epilepsy
- early onset Alzheimer’s disease
What is Edwards syndrome?
Incidence?
Trisomy 18
1 in 8000 live births
Clinical features of Edwards syndrome?
- low birthweight
- prominent occiput
- small mouth and chin
- short sternum
- flexed, overlapping fingers
- ‘rocker bottom’ feet
- cardiac and renal malformations
What is Patau syndrome?
Incidence?
Trisomy 13
1 in 14 000 live births
Clinical features of Patau syndrome?
- structural defect of brain
- scalp defects
- small eyes and other eye defects
- cleft lip and palate
- polydactyly
- cardiac and renal malformations
What is Turner syndrome?
Incidence?
Only occurs in females: 45, X
1 in 2500 live born females
>95% results in early miscarriage
How can Turner syndrome be identified antenatally?
USS showing fetal oedema of neck, hands, or feet and cystic hygroma may be identifies
Clinical features of Turner syndrome?
- lymphoedema of hands and feet in neonate which may persist
- spoon-shaped nails
- short stature
- neck webbing/thick neck
- wide carrying angle
- widely spaced nipples
- congenital heart defects (particularly CoA)
- delayed puberty
- ovarian dysgenesis resulting in infertility, although pregnancy may be possible with IVF using donated ova
- hypothyroidism
- renal anomalies
- pigmented moles
- recurrent otitis media
- normal intellectual function in most cases
Cytogenetics of Turner syndrome?
- 50% have 45, X
Other cases: - deletion of short arm of one X chromosome
- Isochromosome that has 2 long arms but on short arm
- Variety of other structural defects of X chromosomes
- Presence of Y chromosome sequence may increase risk of gonadoblastoma
- incidence does not increase with maternal age and risk of recurrence is very low
Treatment of Turner syndrome?
- growth hormone therapy
- oestrogen replacement for development of secondary sexual characteristics at time of puberty
infertility still persists
What is fragile X syndrome?
Inherited X-linked disorder
A break in the distal part of the long arm of the X chromosome causing significant learning difficulties in males (1 in 4000)
- 2nd most common genetic cause of severe learning difficulties
Characteristics of fragile X syndrome?
- mod-severe learning difficulty
- macrocephaly
- macroorchidism - postpubertal
- long face, large everted ears, prominent mandible, broad forehead
- mitral valve prolapse, joint laxity, scoliosis, autism, hyperactivity
What is Marfan syndrome?
Clinical features?
Later risks?
Autosomal dominant disorder of connected tissue
Tall stature, long thin digits, hyperextensible joints, high arched palate, dislocation of lenses, severe myopia. May be chest deformity and scoliosis.
Major probs - cardiovascular: mitral valve prolapse and regurg; aneurysms of aorta may dissect or rupture
What is Rett syndrome?
Rare genetic neurological and developmental disorder that affects the way the brain develops, causing progressive inability to use muscles for eye and body movements and speech.
Occurs almost exclusively in girls
Seem to develop normally at first but after 6months lose skills they previously had - crawling, walking, communicating, using hands
