Chromosomal Syndromes Flashcards
Define Down’s Syndrome.
Trisomy 21
Define Edward’s Syndrome.
Trisomy 18
Define Patau Syndrome.
Trisomy 13
Define Noonan Syndrome.
Autosomal dominant condition on chromosome 12
Define Turner Syndrome.
45, XO
Genetic defect, in females, resulting from the complete or partial absence of an X chromosome
Define Klinefelter Syndrome.
47, XXY
Genetic defect of the sex chromosomes in males leading to a karyotype of 47XXY (80–90% of cases) or more rarely a mosaic of 46XY/47XXY.
Define Prader-Willi Syndrome.
Imprinting disorder affecting the paternal copy of chromosome 15.
(Paternal Prader-Willi)
Explain the aetiology/risk factors for Down’s Syndrome.
- Non-disjunction at meiosis (95%): Extra maternal chromosome: karyotype 47XX þ 21 or 47XYþ21. Increased incidence of trisomy 21 secondary to non-dysjunction with increasing maternal age, especially >35 years and is independent of paternal age.
- Robertsonian translocation (4%): Chromosome 21 usually translocated onto chromosome 14.
- Mosaicism (1%): Some cells normal, some trisomy 21 due to non-dysjunction during mitosis after fertilization; usually less severely affected.
What is Down’s Syndrome associated with?
- Congenital heart disease (40%): AVSD, VSD, ASD, Fallot tetralogy, PDA.
- Gastrointestinal: Anal, oesophageal and duodenal atresia (one-third of infants with duodenal atresia are syndromic), Hirschsprung’s disease.
- Chronic secretory otitis media: Gives rise to conductive hearing loss.
- Others: Recurrent respiratory infections, cataracts, squints, hypothyroidism
Explain the aetiology/risk factors for Edward’s Syndrome and Patau Syndrome.
Similar to Down’s Syndrome
Explain the aetiology for Noonan Syndrome.
Autosomal dominant inheritance.
De novo mutations are possible.
Explain the aetiology of Turner Syndrome.
Classic TS: 45XO.
Mosaic TS: 45X0/46XX and rarely 45X0/46XY.
Two-thirds of classic TS lack paternal X chromosome. Not all the genes have been identified but loss of one copy of the SHOX gene leads to similar phenotype of short stature and skeletal abnormalities (Leri–Weill dyschondrosteosis).
Explain the aetiology of Klinefelter Syndrome.
Similar to Down’s syndrome.
Can rarely have 48 chromosomes (XXXY or XXYY). Most common reason is non-disjunction events.
Explain the aetiology of Prader-Willi Syndrome.
Deletion of the paternal copies on chromosome 15 which means there are no functional copies of the genes encoded. The mechanism of imprinting only occurs during the development of sperm.
Summarise the epidemiology of Down’s Syndrome.
1/700 live births. Most common genetic cause of learning difficulties. Second affected child is 1/200 if >35 and double the age-specific rate if <35.
Summarise the epidemiology of Edward’s Syndrome.
1 in 5000 live births.
Summarise the epidemiology of Patau Syndrome.
1 in 15,000 live births.
Summarise the epidemiology of Noonan Syndrome.
1 in 1000.
Most common genetic disorder associated with congenital heart disease.
Summarise the epidemiology of Turner Syndrome.
1/2500 females.
No race/ethnic trends.
Summarise the epidemiology of Klinefelter Syndrome.
1/1000 males.
Summarise the epidemiology of Prader-Willi Syndrome.
1 in 25,000 newborns.
What are the presenting signs and symptoms for Down’s Syndrome?
General: Neonatal hypotonia, short stature.
Developmental: Mild–moderate learning disability (IQ 25–70, with social skills exceeding other intellectual functions).
Craniofacial: Microcephaly, brachycephaly (shortness of skull), round face, epicanthic folds, upward sloping palpebral fissures, protruding tongue, flat nasal bridge, small ears, excess skin at back of neck, atlantoaxial instability.
Eyes: Strabismus, nystagmus, Brushfield spots in iris, cataracts.
Limbs: Fifth finger clinodactyly, single palmar crease, wide gap between first and second toes (saddle toes), hyperflexible joints in infants.
CVS: Murmurs dependent on congenital heart disease, arrhythmias, signs of heart failure.
GI: Constipation.
