Down Syndrome

Causes

• 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

• 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

• 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

• 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.

Adult Health Care in Down Syndrome

Adults with Down syndrome now commonly live into their sixties, and their medical needs shift to conditions that arrive earlier and more often than in the general population. Most are treatable, and several are easy to miss because they present as a change in behavior rather than a complaint.

Thyroid: checked every year, for life

Hypothyroidism becomes progressively more common with age in Down syndrome, often from Hashimoto's thyroiditis, and its symptoms of slowing, weight gain, and low mood are easily attributed to the syndrome itself. An annual thyroid blood test is standard, and levothyroxine replacement is straightforward once it is found. Overactive thyroid and celiac disease are also more frequent and are tested for when symptoms suggest them.

Sleep apnea is the rule rather than the exception

The airway anatomy and low muscle tone of Down syndrome make obstructive sleep apnea extremely common in adults, and it drives daytime sleepiness, irritability, and cognitive decline that are otherwise unexplained. A sleep study is worth arranging even without loud snoring, and treatment often visibly improves energy and behavior; our sleep apnea diagnosis guide explains the process.

Hearing, vision, and the heart

Hearing loss from earwax, middle-ear fluid, or aging, and vision loss from cataracts, keratoconus, or an uncorrected prescription, appear earlier and are checked every one to two years, because either can look like withdrawal or decline. Adults who had heart surgery in childhood need periodic cardiology follow-up, and acquired valve disease can develop even in those born with normal hearts.

Alzheimer's disease comes early, and is not the first explanation

Because the gene for amyloid sits on chromosome 21, most adults with Down syndrome develop Alzheimer's-type brain changes by their forties and many develop Alzheimer's disease in their fifties. A baseline assessment of function and abilities around age 35 to 40, repeated annually, allows real change to be recognized. Any decline is first checked for the reversible mimics, including thyroid disease, sleep apnea, hearing loss, depression, vitamin B12 deficiency, and pain, before dementia is diagnosed. Our dementia warning signs article describes the changes families notice first.

Bones, weight, mood, and the neck

Low bone density, obesity, and depression are all more common, and each is screened for and treated as in anyone else. Neck pain, a change in walking, or new clumsiness prompts imaging for atlantoaxial instability. Our endocrine team manages thyroid and bone health within a coordinated adult care plan. The NICHD and the National Institute on Aging publish guidance on adult health and Alzheimer's disease in Down syndrome.

If an adult with Down syndrome in your family has not had a thyroid test, hearing and vision check, or baseline cognitive assessment in the past year, schedule a visit.