Down Syndrome

Down syndrome is a genetic disorder caused by the presence of an extra full or partial copy of chromosome 21. This additional genetic material leads to a combination of physical characteristics, intellectual disabilities, and developmental delays. Down syndrome is the most common chromosomal disorder in humans and a leading cause of intellectual disability. The severity of intellectual disability and developmental problems varies among individuals with Down syndrome, ranging from mild to moderate. Individuals with Down syndrome also have a higher risk of certain medical conditions, such as heart defects, gastrointestinal issues, and thyroid problems.

Causes:

Down syndrome is caused by a chromosomal abnormality, specifically an extra copy of all or part of chromosome 21. There are three main types of Down syndrome, differing in the way the extra chromosome 21 arises.

• Trisomy 21 (Nondisjunction):
  • This is the most common type, accounting for about 95% of cases.
  • It occurs when there is an error in cell division (nondisjunction) during the formation of the egg or sperm cell. This results in an embryo with three copies of chromosome 21 instead of the usual two.
  • This error is typically spontaneous and not inherited from parents.
• Translocation Down Syndrome:
  • Accounts for about 3-4% of cases.
  • In this type, a portion of chromosome 21 breaks off and attaches to another chromosome (often chromosome 14, 21, or 22), either before or at conception.
  • Unlike Trisomy 21, this type can be inherited from a parent who carries a balanced translocation (meaning they have the rearranged chromosome but no extra genetic material, so they do not have Down syndrome themselves).
• Mosaic Down Syndrome:
  • The rarest form, accounting for about 1-2% of cases.
  • Occurs when nondisjunction happens in one of the initial cell divisions after fertilization.
  • This results in a mixture of two types of cells: some with the usual two copies of chromosome 21 and some with three copies.
  • Individuals with mosaic Down syndrome may have milder characteristics of the condition.
• Risk Factors:
  • Maternal Age: A woman’s chance of giving birth to a child with Down syndrome increases with age, particularly after 35.
  • Having One Child with Down Syndrome: Increases the likelihood of having another child with Down syndrome.
  • Being a Carrier of the Genetic Translocation: If a parent carries the genetic translocation for Down syndrome, they can pass it on to their child, leading to translocation Down syndrome.

Symptoms and Characteristics:

Down syndrome is associated with a range of physical characteristics and developmental challenges. The severity varies greatly among individuals.

• Physical Characteristics:
  • Flattened facial profile.
  • Small head and ears.
  • Short neck.
  • Protruding tongue.
  • Upward slanting eyes (palpebral fissures).
  • Unusually shaped or small ears.
  • Poor muscle tone (hypotonia).
  • Broad, short hands with a single crease in the palm (simian crease).
  • Relatively short fingers and small hands and feet.
  • Excessive flexibility.
  • Tiny white spots on the iris (Brushfield spots).
• Intellectual and Developmental Delays:
  • Mild to moderate intellectual disability.
  • Delayed language and speech development.
  • Delayed motor skills (e.g., sitting, crawling, walking).
  • Challenges with reasoning and judgment.
• Associated Medical Conditions (Higher Risk):
  • Heart Defects: Congenital heart defects are common.
  • Gastrointestinal Defects: Intestinal blockages, celiac disease.
  • Thyroid Problems: Hypothyroidism (underactive thyroid).
  • Immune System Deficiencies: Increased susceptibility to infections.
  • Vision and Hearing Problems: Cataracts, strabismus (crossed eyes), hearing loss.
  • Leukemia: A higher risk, particularly acute myeloid leukemia in infancy.
  • Sleep Apnea: Due to soft tissue and skeletal changes.
  • Obesity.
  • Atlantoaxial Instability: Misalignment of the top two vertebrae in the neck.
  • Early Onset Alzheimer’s Disease: Individuals with Down syndrome are at increased risk of developing Alzheimer’s-like brain changes in middle age.

Diagnosis:

Down syndrome can be diagnosed during pregnancy or after birth through chromosomal analysis.

• During Pregnancy (Prenatal Screening and Diagnostic Tests):
  • Screening Tests (non-invasive): Estimate the risk of Down syndrome. They do not diagnose the condition.
    • First Trimester Combined Screen: Blood test (PAPP-A and hCG levels) and nuchal translucency (NT) ultrasound.
    • Second Trimester Quad Screen: Blood test (AFP, hCG, estriol, inhibin A levels).
    • Non-Invasive Prenatal Testing (NIPT)/Cell-Free DNA Testing: A blood test that analyzes fetal DNA in the mother’s blood. Highly accurate for screening.
  • Diagnostic Tests (invasive): Provide a definitive diagnosis by analyzing the baby’s chromosomes.
    • Amniocentesis: A sample of amniotic fluid is taken and analyzed (typically after 15 weeks).
    • Chorionic Villus Sampling (CVS): A sample of tissue from the placenta is taken and analyzed (typically between 10-13 weeks).
• After Birth:
  • Physical Appearance: Doctors often suspect Down syndrome based on the baby’s physical characteristics at birth.
  • Karyotype Test: A blood sample is taken, and the chromosomes are analyzed to confirm the presence of an extra chromosome 21 and determine the type of Down syndrome (Trisomy 21, translocation, or mosaicism). This is the definitive diagnostic test.

Treatment and Management:

There is no cure for Down syndrome, but early intervention, supportive therapies, and medical management of associated health conditions can significantly improve the quality of life and developmental outcomes for individuals.

• Early Intervention Programs:
  • Crucial for promoting development and maximizing potential.
  • Includes physical therapy (to improve motor skills and muscle tone).
  • Speech therapy (to improve communication and language skills).
  • Occupational therapy (to develop daily living and fine motor skills).
  • Special education services tailored to individual learning needs.
• Medical Management of Associated Conditions:
  • Regular Medical Check-ups: To monitor for and address potential health issues (heart, thyroid, vision, hearing, gastrointestinal).
  • Cardiac Care: Surgery for congenital heart defects if necessary.
  • Thyroid Hormone Replacement: For hypothyroidism.
  • Vision and Hearing Correction: Glasses, hearing aids, or surgery as needed.
  • Nutritional Guidance: To prevent obesity and manage gastrointestinal issues.
  • Monitoring for Atlantoaxial Instability: Regular screenings.
• Therapies and Support:
  • Behavioral Therapy: To address behavioral challenges.
  • Social Skills Training: To enhance social interactions.
  • Family Support: Connecting with support groups and resources for families.
  • Inclusive Education: Promoting inclusion in mainstream educational settings where appropriate.
• Transition to Adulthood:
  • Vocational training and job support.
  • Independent living skills training.
  • Continued healthcare management.

With comprehensive and individualized care, individuals with Down syndrome can lead fulfilling lives and be active members of their communities.