Down syndrome is a chromosomal abnormality caused by the presence of a third (partial or total) copy of chromosome 21 and that is characterized by variable intellectual disability, muscular hypotonia, and joint laxity, often associated with a characteristic facial dysmorphism and various anomalies such as cardiac, gastrointestinal, or endocrine defects.
Although trisomy 21 is not rare, the prevalence in the general population has decreased significantly as a result of routine prenatal testing. The prevalence at birth in France is currently estimated at 1/1570 live births, and in Europe at 1/1,020.
Variable and often mild intellectual disability, almost constant muscular hypotonia and joint laxity are often associated with morphological signs, malformations and risks of complications. Morphological features (upslanting palpebral fissures, epicanthus, flat neck, round face, small nose, bilateral single palmar crease) can be mild and do not constitute a hallmark of the condition. The main potential malformations and complications include: short stature, congenital cataract, conductive hearing loss, heart defects (atrio-ventricular canal), digestive malformations (duodenal atresia), Hirschsprung disease, West syndrome (see these terms), seizures, sleep apnea, sensory deficiencies, leukemia, auto-immune and endocrine pathologies (hypothyroidism, celiac disease (see this term), diabetes mellitus type 1, alopecia areata, earlier aging and Alzheimer disease.
In 95% of the cases, trisomy 21 is ``free'': the extra chromosome is due to an accidental non-disjunction during meiosis. 2-3% of those cases are in a mosaic state. In the remaining 5%, the supernumerary chromosome 21 or portion of chromosome 21 is translocated to another chromosome.
The diagnosis is based on karyotyping.
Differential diagnosis includes Zellweger syndrome, 9qter deletion (see these terms) or other chromosomal abnormalities.
In 70-75% of fetuses, increased nuchal translucency can be seen on first-trimester ultrasonography. On the second-trimester, malformations (essentially cardiac and digestive) are present in 60% of the cases, and can be associated with minor morphological signs. Prenatal diagnosis can be confirmed by fetal karyotype on amniocentesis or chorionic villous sampling. Non-invasive prenatal diagnosis on maternal blood is now available in several countries in case of an increased risk of Down syndrome on prenatal screening.
For the parents of a child affected by free trisomy 21, the recurrence risk is only slightly modified (1% until the age of 40 years, linked to maternal age afterwards). In case of Down syndrome caused by translocation, the risk is raised only if one of the parents has a balanced rearrangement. For a person with Down syndrome, the risk of transmitting the disease to the descendants is 1/3.
Early physiotherapy, psychomotor therapy and speech therapy (including alternative non verbal communication tools, namely sign language and picture exchange, in order to stimulate early communication and induce oral skills) are essential. A person with Down syndrome should be involved as soon as possible in decision-making through self-determination. A well-adapted program, including re-education, schooling and social aspects, should be proposed, aiming at obtaining the best possible integration in society. Neuropsychological evaluations are important to recognize the specific dificulties and abilities of each person with Down syndrome and thus propose cognitive remediation. An adapted medical follow-up is useful. It can be necessary to maintain some support in the adult age, including re-education. Research in medical treatment to improve cognition in people with Down syndrome is active with ongoing clinical trials.
Median life expectancy is now above the age of 55 years.
Last update: September 2014
- Dr Bénédicte DE FREMINVILLE
- Dr Renaud TOURAINE