Down Syndrome (Trisomy 21)

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management | References

Definition

Down Syndrome (Trisomy 21) is a genetic condition caused by the presence of an extra copy of chromosome 21. It is the most common chromosomal disorder, affecting physical growth, cognitive development, and overall health. Children with Down syndrome have distinct facial features, developmental delays, and a higher risk of certain medical conditions, including heart defects, respiratory issues, and gastrointestinal abnormalities.

Aetiology

Down Syndrome is caused by the presence of an extra copy of chromosome 21, either in full or in part. There are three types of Down Syndrome:

• Trisomy 21: This is the most common form, where all cells in the body have an extra copy of chromosome 21. It occurs due to nondisjunction during the formation of reproductive cells.
• Mosaic Down Syndrome: In this rarer form, some cells have an extra copy of chromosome 21, while others have the normal number of chromosomes.
• Translocation Down Syndrome: This occurs when a portion of chromosome 21 attaches to another chromosome, usually chromosome 14. This can be inherited from a parent.

Pathophysiology

Down Syndrome results from the presence of an extra chromosome 21 in the genetic material of an individual’s cells. This additional genetic material causes an overexpression of certain genes, leading to the characteristic physical and intellectual features of Down Syndrome. The specific genes affected on chromosome 21 are involved in various developmental processes, leading to cognitive delays, physical growth impairments, and an increased risk of medical conditions such as congenital heart defects, immune dysfunction, and hypothyroidism.

Risk Factors

• Maternal Age: The risk of having a child with Down Syndrome increases with maternal age, particularly in mothers over the age of 35.
• Previous Child with Down Syndrome: Parents who have had one child with Down Syndrome have a slightly increased risk of having another child with the condition.
• Parental Translocation: If one parent carries a translocation involving chromosome 21, the risk of having a child with Down Syndrome increases.

Signs and Symptoms

Children with Down Syndrome exhibit a combination of characteristic physical features, developmental delays, and potential medical complications. Common signs and symptoms include:

• Physical features: Flat facial profile, upward slanting eyes, small ears, short neck, and a single palmar crease across the hand.
• Hypotonia: Low muscle tone, often noticeable in infancy.
• Developmental delays: Delayed milestones, including walking, speaking, and cognitive development.
• Cognitive impairment: Intellectual disability, with varying levels of severity.
• Congenital heart defects: Around 50% of children with Down Syndrome have congenital heart defects, such as atrioventricular septal defects (AVSD).
• Hearing and vision problems: Increased risk of hearing loss and vision issues, including cataracts and strabismus.
• Gastrointestinal issues: Increased likelihood of conditions such as duodenal atresia, Hirschsprung's disease, and constipation.
• Thyroid disorders: Hypothyroidism is common in children with Down Syndrome.

Investigations

Diagnosis of Down Syndrome is often made prenatally or postnatally using the following methods:

• Prenatal screening: Combined screening tests (blood tests and ultrasound) are offered during pregnancy to assess the risk of Down Syndrome.
• Chorionic villus sampling (CVS) or amniocentesis: These invasive diagnostic tests can confirm the diagnosis prenatally by analysing the fetal chromosomes.
• Postnatal karyotyping: A blood test is performed to analyse the baby’s chromosomes and confirm the presence of an extra chromosome 21.
• Additional investigations: If Down Syndrome is diagnosed, further assessments are carried out to identify potential associated conditions (e.g., echocardiogram to detect heart defects, hearing tests, thyroid function tests).

Management

There is no cure for Down Syndrome, but early intervention and supportive care can greatly improve the quality of life for affected children. Management includes:

Medical Management:

• Cardiology: Regular monitoring and management of congenital heart defects, often requiring surgical intervention.
• Thyroid management: Regular screening for hypothyroidism, with appropriate treatment when needed.
• Gastrointestinal management: Monitoring and treating gastrointestinal conditions such as duodenal atresia or constipation.
• ENT care: Regular hearing assessments and management of recurrent ear infections or hearing loss.

Developmental Support:

• Early intervention programmes: These programmes offer speech therapy, physiotherapy, and occupational therapy to support developmental milestones and cognitive function.
• Educational support: Special educational support plans can help children with Down Syndrome in mainstream or specialist school settings.
• Speech and language therapy: This can help improve communication skills, which may be delayed in children with Down Syndrome.

Multidisciplinary Approach:

Children with Down Syndrome benefit from a multidisciplinary team approach involving paediatricians, cardiologists, speech therapists, physiotherapists, and special educators. Regular health check-ups and developmental assessments are essential for managing associated health problems and promoting optimal development.

References

1. NICE (2024). Management of Down Syndrome. Available at: NICE Guidance
2. Down's Syndrome Association (2023). Supporting Children with Down Syndrome. Available at: Down's Syndrome Association
3. British Medical Journal (BMJ). (2022). Diagnosis and Management of Down Syndrome. Available at: BMJ