Download Down Syndrome

Down Syndrome
Rate this Article Email to a Colleague
History
In 1866, Down described clinical characteristics of the syndrome that now bears his name.
In 1959, Lejeune and Jacobs et al., independently determined that Down syndrome is caused by trisomy 21.
Frequency
Down syndrome is by far the most common and best known chromosome disorder in humans.
 In Japan: 1 per 700 live births.
 In the US: 1 per 600-700 live births.
 In Sudan?
 Approximately 6000 children are born with Down syndrome annually.
Mortality and morbidity
 75% of conceptions with trisomy 21 die in embryonic or fetal life.
 85% of infants survive to 1 year and 50% can be expected to live longer than 50 years.
 The male/female ratio is increased (approximately 1.15:1) in newborns with Down syndrome.
Maternal Age
Remains the only well-documented risk factor.
 20 years or younger risk is 1 per 2500 births.
 35 years risk is 1 in 385.
 40 years risk is 1 in 106.
 45 years or older risk is 1 per 30-55 live births.
Cytogenetic changes (Figure 1-4)
1. Full trisomy 21 in 94% of cases.
2. Translocations in 3.3% of cases.
 75% are unbalanced translocations are de novo.
 25% result from familial (maternal or paternal) translocation.
3. Mosaicism in 2.4% of cases.
Most mosaic cases result from a trisomic zygote with mitotic loss of 1 chromosome.
Molecular consequences of chromosomal changes
Analysis revealed that the 21q22.1-q22.3 region appears to contain the gene(s) responsible for the
congenital heart disease observed in Down syndrome. DSCR1 mapped to locus 21q22.1-q22.2 is highly
Imad Fadl-Elmula - Al Neelain University
expressed in the brain and the heart and thus it is the candidate gene for involvement in the pathogenesis of
Down syndrome, in particular, the mental retardation and/or cardiac defects.
Clinical features
1. Growth and mental retardation.
2. Craniofacial abnormalities
3. Flat faces.
4. Small ears.
5. Cardiac abnormality.
6. 11- Hypotonia.
7. 12- The skull is brachycephalic with misshapen.
8. 13- A single palmer crease (Simian crease) present in 50%.
9. 14- Clinodactyly in 50% (little fingers are short and incurved).
15- A wide gab between the first and second toes may be present.
Craniofacial findings
 Small nose.
 Protruding tongue.
 High-arched palate.
 Dental abnormalities.
 Short and broad neck.
 Depressed nasal bridge.
 Flattened head with dysplastic ears.
 Flat occipital and flattened facial appearance.
Face findings
 Short neck.
 Microcephaly.
 Protruding tongue.
 Moon-shaped face.
 Hypertelorism.
 Flat nasal bridge.
 Epicanthus (regressive with age).
 Late appearing/ malformed teeth.
Imad Fadl-Elmula - Al Neelain University
Hands and feet
 Gap between 1st and 2nd toe.
 Flat feet.
 Brachymesophalangia of the 2nd and 5th
fingers.
 First toe et apart from the others by a gap.
 Transverse palmer crease in 75%.
 Clinodactyly of the 5th finger.
Congenital malformations
1. Heart malformation in 40%.
•
Atroventricular canal.
2. Gastrointestinal tract 10%.
•
Duodenal stenosis or atresia.
•
Imperforate anus.
•
Hirschsprungs disease.
Diagnosis of Down Syndrome
Prenatal
 Amniocentesis.
 Percutaneous umbilical blood sampling (PUBS).
 Chorionic villus sampling (CVS).
 Extraction of fetal cells from maternal circulation.
Shortly after birth
1. Dysmorphic features and distinctive phenotype.
2. Cytogenetic analysis and FISH analysis.
 Clinical diagnosis should be confirmed with cytogenetic studies.
 Karyotyping is essential for determination of recurrence risk.
 In translocation Down syndrome, karyotyping of the parents and other relatives is required for proper
genetic counseling.
Imad Fadl-Elmula - Al Neelain University
Genetic counseling
For trisomy 21
The recurrence risk is about 1%.
For de novo Robertsonian translocation:
The risk of Down syndrome in a subsequent pregnancy is estimated at 2-3%.
For Paternal balance translocation
The risk to have a live born Down syndrome is 1 in 3.
In a carrier parent with a 21q21q translocation or isochromosome, the recurrence risk is 100%.
Mosaic Down syndrome: Most mosaic patients derive from trisomy 21 zygotes.
Affected individuals rarely reproduce.
From 15-30% of females with trisomy 21 are fertile and they have a 50% risk of having an affected child.
No evidence exists of an affected male fathering a child.
Consultations:

Clinical geneticist

Developmental pediatrician

Cardiologist

Ophthalmologist

Neurosurgeon

Orthopedic specialist

Psychiatrist

Physical and occupational therapist

Speech-language pathologist

Audiologist
Prognosis
Life expectancy
Reduced.
Mortality from
1. Congenital heart disease.
2. Susceptibility to infections abnormal serum IgG
High incidence of
1. Leukemia.
Imad Fadl-Elmula - Al Neelain University
2. Thyroid diseases.
3. Autoimmune disorders.
4. Alzheimer by age 40 years (75%).
Medical/Legal Pitfalls

Failure to identify characteristic symptoms and signs of Down syndrome and to refer patient to a
geneticist for evaluation and genetic counseling

Failure to obtain chromosome analysis with clinical diagnosis of Down syndrome

Failure to offer prenatal screening for pregnant women

Failure to offer prenatal diagnosis after having an affected child

Reliance on maternal serum triple marker screening for prenatal diagnosis in a pregnancy at
increased risk for Down syndrome (Amniocentesis and CVS are the criterion standard diagnostic
tests for prenatal diagnosis in a pregnancy at increased risk
Imad Fadl-Elmula - Al Neelain University