Down syndrome

Down syndrome
Name	Down syndrome
Synonyms	Down's syndrome, trisomy 21
Caption	Trisomy of chromosome 21 is the most common cause.
Field	Medical genetics, Pediatrics
Symptoms	Intellectual disability, characteristic facial features, growth delays
Complications	Congenital heart defect, hypothyroidism, hearing loss, obstructive sleep apnea
Onset	Conception
Duration	Lifelong
Types	Trisomy 21, Robertsonian translocation, Mosaic Down syndrome
Causes	Third copy of chromosome 21
Risks	Advanced maternal age
Diagnosis	Prenatal screening, amniocentesis, chorionic villus sampling, karyotype
Differential	Zellweger syndrome, Cri du chat syndrome
Prevention	None
Treatment	Early childhood intervention, speech therapy, occupational therapy
Medication	As needed for associated conditions
Prognosis	Life expectancy ~60 years (developed world)
Frequency	~1 in 700 births

Down syndrome. It is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is typically associated with physical growth delays, mild to moderate intellectual disability, and characteristic facial features. The condition's effects and severity can vary widely among individuals.

Signs and symptoms

Common physical traits include a flattened facial profile, upward-slanting palpebral fissures, a protruding tongue, and a single palmar crease. Many individuals experience hypotonia and joint ligamentous laxity. Associated medical conditions are frequent, including congenital heart disease such as atrioventricular septal defect, gastrointestinal issues like Hirschsprung's disease, and otitis media. Vision problems such as cataract and refractive error are common, as is obstructive sleep apnea. Developmental milestones, including speech and motor skills, are often delayed.

Causes

The primary cause is the presence of an extra copy of genetic material from chromosome 21. In approximately 95% of cases, this results from nondisjunction during meiosis, leading to full trisomy 21. About 4% of cases are due to a Robertsonian translocation, where part of chromosome 21 attaches to another chromosome, often chromosome 14. The remaining cases are mosaic Down syndrome, where only some cells carry the extra chromosome. The only well-established risk factor is advanced maternal age, particularly in women over 35, though younger mothers have more total births of children with the condition.

Diagnosis

Suspicion may arise from prenatal screening tests, such as the combined first-trimester test analyzing maternal serum and nuchal translucency ultrasound. Cell-free fetal DNA testing from maternal blood offers high sensitivity. Definitive prenatal diagnosis is achieved through invasive procedures like amniocentesis or chorionic villus sampling and subsequent karyotype analysis. After birth, the diagnosis is often clinically suspected based on physical examination and confirmed by a chromosomal analysis of the child's lymphocytes.

Management

There is no cure; management focuses on treating associated conditions and supporting development. This typically involves a multidisciplinary team including pediatricians, cardiologists, and endocrinologists. Early childhood intervention programs are critical, often incorporating physical therapy, occupational therapy, and speech-language pathology. Surgical correction may be required for heart defects or duodenal atresia. Regular screening for common issues like hypothyroidism, celiac disease, and atlantoaxial instability is standard. Educational support is provided through Individualized Education Programs in schools.

Prognosis

Life expectancy has increased dramatically, now averaging around 60 years in the developed world, largely due to improved cardiac care and treatment of infections. Individuals lead fulfilling lives, though they are at increased risk for early-onset Alzheimer's disease, often linked to the APP gene on chromosome 21. Many achieve varying levels of independence, with some holding paid employment and living in supported living arrangements. The Global Down Syndrome Foundation and the National Down Syndrome Society advocate for health, research, and inclusion.

Epidemiology

It occurs in about 1 in 700 live births globally, making it the most common chromosomal abnormality. Prevalence at birth is influenced by maternal age demographics and prenatal screening practices; in countries with widespread screening and termination, live birth prevalence has decreased. Notable individuals with the condition include the Spanish actor Pablo Pineda and the American advocate and model Madeline Stuart. Research organizations like the Linda Crnic Institute for Down Syndrome and the Anna and John J. Sie Center for Down Syndrome conduct ongoing medical studies.

Category:Genetic disorders Category:Chromosomal abnormalities Category:Conditions diagnosed by prenatal testing