Down Syndrome

Mr. Arvind Kumar

Introduction

  1. Down Syndrome (Trisomy 21) is a genetic disorder caused by having an extra copy of chromosome 21.

  2. Normally, every person has 46 chromosomes (23 pairs). In Down’s Syndrome, there are 47 chromosomes because chromosome 21 is triplicated.

  3. It leads to mental retardation (intellectual disability), growth delay, distinct facial features, and various health problems.

  4. It was first described by Dr. John Langdon Down in 1866, and the extra chromosome 21 was discovered by Dr. Jérôme Lejeune in 1959.

  5. It is the most common chromosomal abnormality seen in newborns.

Genetic Basis (Cause)

Down’s Syndrome occurs because of extra genetic material from chromosome 21.
There are three main genetic types:

Type Genetic Mechanism Frequency (%) Key Points
Trisomy 21 (Nondisjunction) Failure of chromosome 21 to separate during egg/sperm formation (meiosis) 95% Most common type; not inherited
Translocation Extra part of chromosome 21 attaches to another chromosome (commonly 14 or 22) 3–4% May be inherited from parent
Mosaicism Some cells have normal 46 chromosomes; others have 47 1–2% Symptoms are milder

🔹 Nondisjunction

  • Happens when chromosome 21 fails to separate properly during egg/sperm formation.

  • This gives an extra copy of 21 in the baby.

  • Increases with maternal age, especially >35 years.

🔹 Translocation

  • The total chromosome number remains 46, but extra material from chromosome 21 is attached to another chromosome.

  • One parent may carry a balanced translocation, increasing recurrence risk.

🔹 Mosaicism

  • Caused by an error in cell division after fertilization.

  • Some cells are normal, others have trisomy 21 — so symptoms are less severe.

 

Epidemiology

 

Parameter Details
Incidence 1 in every 700 live births
Gender ratio Equal in males and females
Maternal age risk ↑ Higher after 35 years
Inheritance Mostly non-inherited (sporadic)

 

Clinical Features

A. Physical Features

System Features
Face and Head Flat facial profile, small nose, upward slanting eyes, epicanthic folds, small mouth with protruding tongue, small ears
Hands and Feet Single palmar crease (“Simian crease”), short broad hands, wide gap between big and second toe
Neck Short neck with loose skin folds
Body Short stature, overweight tendency, soft muscle tone (hypotonia) in infancy
Hair/Skin Dry skin, fine straight hair
Other Delayed closure of fontanelles, small chin, broad flat skull

 

B. Mental and Developmental Features

  • Mild to moderate intellectual disability (IQ 25–70)

  • Delayed milestones (late sitting, walking, talking)

  • Speech delay and learning difficulties

  • Friendly, cheerful, affectionate behavior

  • Good visual learning and social understanding

C. Medical Problems Common in Down’s Syndrome

System Common Problems
Heart Congenital heart defects (Atrioventricular septal defect, ASD, VSD) – seen in 40–50%
Gastrointestinal Duodenal atresia, Hirschsprung’s disease, constipation
Endocrine Hypothyroidism (common)
Blood Increased risk of leukemia (especially acute lymphoblastic leukemia)
Nervous system Early Alzheimer’s-like dementia
Vision/Hearing Strabismus, cataract, hearing loss
Immunity Prone to infections
Musculoskeletal Joint laxity, short limbs

 

Pathophysiology

 

Cause Effect
Extra chromosome 21 Overexpression of many genes
Gene imbalance Affects brain, heart, and growth
Overproduction of certain proteins Leads to developmental and immune problems
Example genes: SOD1, APP, DYRK1A Cause oxidative stress, Alzheimer-like changes, and delayed brain development

Laboratory and Diagnostic Tests

1. Prenatal Screening Tests

Used to detect high-risk pregnancies before birth.

Test Name Timing Components Interpretation
First Trimester Screening 11–13 weeks Ultrasound (nuchal translucency) + PAPP-A + β-hCG ↑ hCG, ↓ PAPP-A suggest risk
Second Trimester Quadruple Test 15–20 weeks AFP, hCG, Estriol, Inhibin-A ↓ AFP, ↓ Estriol, ↑ hCG, ↑ Inhibin-A = risk
Non-Invasive Prenatal Testing (NIPT) Any time after 10 weeks Cell-free fetal DNA in maternal blood Highly accurate

 

2. Confirmatory Diagnostic Tests

Test Description Timing
Chorionic Villus Sampling (CVS) Tests placental cells for karyotype 10–12 weeks
Amniocentesis Tests amniotic fluid for chromosomal study 15–18 weeks
Karyotyping Confirms extra chromosome 21 Any stage
FISH / Microarray Rapid detection of specific chromosome changes Used for confirmation

 

3. Postnatal Diagnosis

  • Based on physical features + confirmed by karyotype (47, XX+21 or 47, XY+21).

  • Newborns are screened for heart, thyroid, hearing, and vision defects.

 

Management and Treatment

There is no permanent cure, but early management and lifelong care can greatly improve quality of life.

A. Medical Management

Problem Management
Heart defects Early surgery and cardiology follow-up
Hypothyroidism Thyroid hormone replacement
Infections Regular vaccination, antibiotics as needed
Leukemia risk Routine blood monitoring
Vision/Hearing Corrective lenses, hearing aids
GI problems Surgical correction if required

 

B. Developmental Support

  • Early intervention programs: Speech, physical, and occupational therapy from infancy.

  • Special education: Tailored learning plans and visual aids.

  • Social skill training: Improves independence and self-confidence.

  • Behavioral therapy: For discipline and emotional control.

C. Family and Genetic Counselling

Aspect Details
Parental education Explainsthe  nature of disorder and realistic expectations
Genetic counseling Especially for translocation cases
Recurrence risk About 1% for nondisjunction; up to 10–15% for translocation carriers
Emotional support Support groups and special care organizations help parents cope

 

Prognosis

 

Parameter Outcome
Life expectancy Improved — around 55–60 years with medical care
Quality of life Good with therapy and social inclusion
Complications Heart defects, thyroid issues, infections, early aging
Survival improvement factors Early detection, surgery, parental care, education

 

Prevention

  1. Genetic counseling before pregnancy, especially if mother >35 years.

  2. Prenatal screening and testing during pregnancy.

  3. Avoiding late maternal age pregnancy.

  4. Use of assisted reproductive technology (PGD) for high-risk couples.

  5. Folic acid supplementation and general maternal care improve outcomes.

 

MCQs

  1. Down’s Syndrome is also known as:
    A. Trisomy 18
    B. Trisomy 21
    C. Trisomy 13
    D. Monosomy X

  2. Down’s Syndrome is caused by:
    A. Mutation in a single gene
    B. Deletion of a chromosome
    C. Extra copy of chromosome 21
    D. Lack of chromosome 21

  3. The total number of chromosomes in a person with Down’s Syndrome is:
    A. 45
    B. 46
    C. 47
    D. 48

  4. The genetic defect in Down’s Syndrome is due to:
    A. Nondisjunction
    B. Crossing over
    C. Gene transposition
    D. Deletion

  5. Down’s Syndrome is a type of:
    A. Sex-linked disorder
    B. Chromosomal disorder
    C. Autosomal dominant disease
    D. Metabolic disorder

  6. The risk of Down’s Syndrome increases with:
    A. Paternal age
    B. Maternal age
    C. Childhood infections
    D. Vitamin deficiency

  7. Which chromosomal abnormality is seen in Down’s Syndrome?
    A. Monosomy
    B. Trisomy
    C. Tetrasomy
    D. Translocation only

  8. The most common type of Down’s Syndrome is:
    A. Mosaic type
    B. Translocation type
    C. Nondisjunction type
    D. Structural type

  9. The most common cause of Down’s Syndrome is:
    A. Nondisjunction of chromosome 21
    B. Deletion of chromosome 21
    C. Insertion of chromosome 21
    D. Fusion of X and Y chromosomes

  10. The syndrome was first described by:
    A. Watson and Crick
    B. John Langdon Down
    C. Gregor Mendel
    D. Jerome Lejeune

  11. The chromosomal cause of Down’s Syndrome was discovered by:
    A. Lejeune
    B. Watson
    C. Morgan
    D. Muller

  12. Characteristic facial feature of Down’s Syndrome is:
    A. Elongated face
    B. Flat facial profile
    C. Large forehead
    D. Pointed chin

  13. Which of the following is a common hand feature in Down’s Syndrome?
    A. Double palmar crease
    B. Single transverse palmar crease (Simian crease)
    C. Extra fingers
    D. Curved nails

  14. Which of the following physical findings is common in Down’s Syndrome?
    A. Long neck
    B. Short neck with skin folds
    C. Large jaw
    D. Long fingers

  15. The muscle tone in Down’s Syndrome infants is usually:
    A. Normal
    B. Increased
    C. Decreased
    D. Variable

  16. Which congenital heart disease is most common in Down’s Syndrome?
    A. Patent ductus arteriosus
    B. Tetralogy of Fallot
    C. Atrioventricular septal defect
    D. Coarctation of aorta

  17. Which type of leukemia is common in Down’s Syndrome?
    A. Chronic lymphocytic leukemia
    B. Acute lymphoblastic leukemia
    C. Chronic myeloid leukemia
    D. Hairy cell leukemia

  18. Down’s Syndrome children commonly have:
    A. Hyperthyroidism
    B. Hypothyroidism
    C. Diabetes
    D. Addison’s disease

  19. Which of the following GI problems may occur in Down’s Syndrome?
    A. Duodenal atresia
    B. Peptic ulcer
    C. Crohn’s disease
    D. Gastritis

  20. Down’s Syndrome individuals are at higher risk of developing:
    A. Alzheimer-like dementia
    B. Parkinson’s disease
    C. Huntington’s disease
    D. Multiple sclerosis

  21. The genetic abnormality in Down’s Syndrome can be confirmed by:
    A. Blood sugar test
    B. Karyotyping
    C. MRI scan
    D. ECG

  22. The karyotype of a Down’s Syndrome female is:
    A. 45, XX
    B. 46, XX
    C. 47, XX, +21
    D. 47, XY, +21

  23. The karyotype of a Down’s Syndrome male is:
    A. 45, XY
    B. 47, XY, +21
    C. 46, XY
    D. 48, XY

  24. Prenatal screening for Down’s Syndrome can be done by:
    A. Urine test
    B. First-trimester ultrasound and biochemical tests
    C. X-ray
    D. Physical exam

  25. Which prenatal test confirms Down’s Syndrome?
    A. Amniocentesis
    B. Blood test
    C. Ultrasound only
    D. ECG

  26. In Down’s Syndrome screening, which serum marker is increased?
    A. AFP
    B. Estriol
    C. hCG
    D. PAPP-A

  27. Which serum marker is decreased in Down’s Syndrome?
    A. hCG
    B. Inhibin A
    C. Estriol
    D. LDH

  28. Non-Invasive Prenatal Testing (NIPT) detects:
    A. Maternal hormones
    B. Fetal DNA in maternal blood
    C. Placental enzymes
    D. Amniotic proteins

  29. Which of the following is NOT a typical feature of Down’s Syndrome?
    A. Upward slanting eyes
    B. Short stature
    C. Tall and thin body
    D. Flat face

  30. The IQ level of most Down’s Syndrome individuals is:
    A. Normal
    B. Mild to moderate mental retardation
    C. Severe retardation
    D. Superior intelligence

  31. Mosaic type Down’s Syndrome means:
    A. All cells have extra chromosome 21
    B. Only some cells have extra chromosome 21
    C. No extra chromosome present
    D. All chromosomes are duplicated

  32. In translocation Down’s Syndrome, the extra chromosome 21 is attached to:
    A. Chromosome 22
    B. Chromosome 13 or 14
    C. Chromosome 18
    D. Chromosome 1

  33. Life expectancy in modern times for Down’s Syndrome individuals is around:
    A. 10 years
    B. 20 years
    C. 50–60 years
    D. 80–90 years

  34. Early intervention for Down’s Syndrome includes:
    A. Surgery only
    B. Speech, physical, and occupational therapy
    C. Blood transfusion
    D. Hormone replacement

  35. Which of the following preventive measures helps reduce the risk of Down’s Syndrome?
    A. Regular exercise
    B. Avoiding smoking
    C. Genetic counseling and prenatal testing
    D. Protein-rich diet

Answer Key

  1. B — Trisomy 21

  2. C — Extra copy of chromosome 21

  3. C — 47

  4. A — Nondisjunction

  5. B — Chromosomal disorder

  6. B — Maternal age

  7. B — Trisomy

  8. C — Nondisjunction type

  9. A — Nondisjunction of chromosome 21

  10. B — John Langdon Down

  11. A — Lejeune

  12. B — Flat facial profile

  13. B — Single transverse palmar crease (Simian crease)

  14. B — Short neck with skin folds

  15. C — Decreased

  16. C — Atrioventricular septal defect

  17. B — Acute lymphoblastic leukemia

  18. B — Hypothyroidism

  19. A — Duodenal atresia

  20. A — Alzheimer-like dementia

  21. B — Karyotyping

  22. C — 47, XX, +21

  23. B — 47, XY, +21

  24. B — First-trimester ultrasound and biochemical tests

  25. A — Amniocentesis

  26. C — hCG

  27. C — Estriol

  28. B — Fetal DNA in maternal blood

  29. C — Tall and thin body

  30. B — Mild to moderate mental retardation

  31. B — Only some cells have extra chromosome 21

  32. B — Chromosome 13 or 14

  33. C — 50–60 years

  34. B — Speech, physical, and occupational therapy

  35. C — Genetic counseling and prenatal testing