110 Down Syndrome
110.1 Introduction
Down syndrome, also referred to as Trisomy 21, is the most common chromosomal disorder, characterized by a range of physical, developmental, and cognitive abnormalities. First described by John Langdon Down in 1866, it occurs due to an extra copy of chromosome 21, which results in overexpression of the genes on this chromosome. Affecting approximately 1 in 700 live births worldwide, Down syndrome is seen across all racial, ethnic, and socioeconomic groups. This condition presents with varying degrees of intellectual disability, distinctive physical features, and a predisposition to certain medical conditions. Advances in prenatal screening, early interventions, and supportive care have significantly improved the quality of life and life expectancy for individuals with Down syndrome.
110.2 Definition
Down syndrome is a congenital chromosomal disorder caused by trisomy 21, resulting from an extra chromosome 21 in whole or part. It is a multisystem condition affecting physical development, cognitive abilities, and susceptibility to specific medical disorders. Based on the genetic cause, Down syndrome is classified into three types:
Trisomy 21 (95%): A result of nondisjunction during meiosis, leading to an extra chromosome 21 in all cells.
Translocation (4%): A structural rearrangement where a part of chromosome 21 is attached to another chromosome, often chromosome 14.
Mosaicism (1%): A mixture of normal and trisomic cells due to a post-zygotic nondisjunction event.
110.3 Genetics
The extra genetic material from chromosome 21 disrupts normal development and leads to the phenotypic features of Down syndrome. Chromosome 21 is one of the smallest autosomes and contains around 200–300 genes. Overexpression of key genes contributes to the syndrome’s clinical manifestations. These include:
DYRK1A: Implicated in cognitive impairment.
APP (Amyloid Precursor Protein): Associated with early-onset Alzheimer’s disease.
SOD1 (Superoxide Dismutase 1): Contributes to oxidative stress.
ETS2: May influence craniofacial development.
Advanced maternal age is a significant risk factor due to increased nondisjunction during oocyte maturation. The risk of Down syndrome increases with maternal age, from about 1 in 1,500 at age 20 to 1 in 100 at age 40.
110.4 Clinical Features
Individuals with Down syndrome exhibit a characteristic phenotype along with a range of medical and developmental complications. These include:
Craniofacial Features:
Flat facial profile and nasal bridge
Brachycephaly (short and broad skull)
Upward-slanting palpebral fissures
Epicanthal folds
Low-set, small ears
Protruding tongue and small oral cavity
Musculoskeletal Features:
Hypotonia (generalized low muscle tone)
Short stature
Joint hypermobility
Single transverse palmar crease (Simian crease)
Clinodactyly (inward curvature of the fifth finger)
Neurological and Cognitive Features:
Mild to moderate intellectual disability (average IQ: 50–70)
Delayed developmental milestones (e.g., sitting, walking, and speech)
Early-onset Alzheimer’s disease (in 50% by their 50s)
Congenital Anomalies:
Cardiac: Approximately 50% have congenital heart defects, primarily atrioventricular septal defects (AVSD) and ventricular septal defects (VSD).
Gastrointestinal: Duodenal atresia, Hirschsprung disease, and annular pancreas are common
Medical Comorbidities:
Endocrine: Hypothyroidism is frequently observed.
Hematological: Increased risk of leukemia, particularly acute lymphoblastic leukemia (ALL) and acute megakaryoblastic leukemia (AMKL).
Immunological: Impaired immune responses lead to recurrent infections.
Respiratory: Obstructive sleep apnea due to airway abnormalities.
Ophthalmic: Cataracts, refractive errors, and strabismus.
Auditory: Conductive and sensorineural hearing loss.
110.5 Investigations
Diagnosis of Down syndrome can be made prenatally or postnatally using a combination of clinical evaluation and laboratory tests.
Prenatal Screening:
Non-Invasive Methods:
- First-Trimester Screening: Combines maternal serum markers (β-hCG and PAPP-A) with nuchal translucency measurement via ultrasound.
- Second-Trimester Screening: Measures serum markers like AFP, β-hCG, estriol, and inhibin-A (quadruple test).
- Non-Invasive Prenatal Testing (NIPT): Analyzes cell-free fetal DNA in maternal blood with high sensitivity and specificity.
Invasive Diagnostic Methods:
- Chorionic Villus Sampling (CVS): Performed at 10–13 weeks of gestation.
- Amniocentesis: Performed after 15 weeks of gestation.
- Cordocentesis: Used for advanced gestational age
Postnatal Diagnosis:
- Clinical Evaluation: Characteristic physical features and hypotonia are noted.
- Cytogenetic Testing: Karyotyping confirms the diagnosis by identifying trisomy 21. Fluorescence in situ hybridization (FISH) or chromosomal microarray analysis provides rapid results.
Additional Investigations:
Echocardiogram to detect congenital heart defects.
Thyroid function tests (TSH and free T4) to screen for hypothyroidism.
Complete blood count (CBC) for hematologic abnormalities.
Hearing and vision assessments.
Polysomnography for suspected obstructive sleep apnea.
110.6 Treatment
There is no cure for Down syndrome, but early intervention, medical management, and supportive care can significantly improve outcomes.
Developmental Interventions:
Early therapy programs, including speech, occupational, and physical therapy.
Special education tailored to cognitive abilities and needs.
Medical Management:
Surgical correction of congenital anomalies (e.g., AVSD or duodenal atresia).
Thyroid hormone replacement for hypothyroidism.
Antibiotics for recurrent infections.
Management of obstructive sleep apnea with CPAP or adenotonsillectomy.
Regular follow-up for screening and management of complications like leukemia or Alzheimer’s disease.
Psychosocial Support:
Enabling social inclusion through community programs.
Support groups for families and caregivers.
Promoting independent living skills in adulthood
110.7 Counselling
Comprehensive genetic and psychosocial counseling is essential for families of individuals with Down syndrome.
- Prenatal Counselling:
- Educate expectant parents about the condition, available diagnostic methods, and outcomes.
- Provide psychological support to help them make informed decisions regarding pregnancy continuation or termination.
- Postnatal Counseling:
- Offer guidance on medical care, developmental milestones, and prognosis.
- Address the emotional and social concerns of the family.
- Encourage joining support groups and advocacy networks.
- Genetic Counseling:
- For translocation Down syndrome, parents should undergo karyotyping to determine if one is a carrier of a balanced translocation, which increases the recurrence risk in future pregnancies.
110.8 Conclusion
Down syndrome is a complex chromosomal disorder requiring a multidisciplinary approach to diagnosis, treatment, and management. Advances in prenatal screening and medical care have improved the life expectancy and quality of life for individuals with Down syndrome. However, ongoing research into the genetic and molecular basis of the condition holds promise for novel therapeutic interventions. Holistic care, including medical, developmental, and psychosocial support, is crucial in empowering individuals with Down syndrome to lead fulfilling lives.
110.9 Review Schedule
| Age: Focus Areas | Assessments & Follow-Up | Referral/Intervention |
| Birth – 1 Month: Initial Screening |
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| 1 – 6 Months: Early Development |
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| 6 – 12 Months: Development & Screening |
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| 1 – 2 Years: Cognitive & Physical Growth |
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| 2 – 5 Years: School Readiness |
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| 5 – 10 Years: Academic, Social, and Health Monitoring |
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| 10 – 13 Years: Puberty & Social Development |
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| 13 – 16 Years: Transition Planning |
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