Downs syndrome

Related Subjects: | Osteoporosis | Autosomal Dominant | Autosomal Recessive | X Linked Recessive |Dementias |Chromosomal Defects |Turner's syndrome (Children) |Down's syndrome (Children)

🧬 Down's Syndrome is usually caused by a nondisjunction event, where chromosome 21 fails to separate during gamete formation. This results in an embryo with three copies of chromosome 21 (trisomy 21) instead of the usual two.

⚙️ Aetiology

1. ➕ Non-disjunction (≈94%): All cells have an extra chromosome 21. Strongly linked with increasing maternal age 👩‍🦳.
2. 🧩 Mosaicism (≈2%): Only some cells carry trisomy 21 → usually milder phenotype.
3. 🔗 Robertsonian Translocation (≈4%): Extra chromosome 21 material attached to another chromosome. Can be inherited, so parental karyotyping may be required.

🧑‍⚕️ Clinical Features

• 🙂 Distinct facies: flattened nasal bridge, small ears/mouth, epicanthic folds.
• 👋 Hands & eyes: single palmar crease, Brushfield spots in iris ✨.
• 📏 Growth & tone: short stature, short neck, flat occiput, hypotonia.
• ❤️ Congenital heart defects: ASD, AVSD, PDA, Tetralogy of Fallot.
• 🍽️ GI anomalies: duodenal atresia, Hirschsprung’s disease (“double bubble” sign on USS).
• 🧠 Intellectual disability: variable severity, usually mild–moderate.

📅 Long-Term Considerations

• 🩸 ↑ Risk of leukaemia (ALL, AML).
• 🦋 Endocrine: hypothyroidism, coeliac disease.
• ⚡ Neurology: epilepsy, early-onset Alzheimer’s disease.
• 👂 ENT/respiratory: recurrent infections, hearing and vision impairment.
• 🍔 GI: duodenal atresia, Hirschsprung’s disease (recurring complications).
• ⚖️ Obesity & metabolic concerns in later life.

🔍 Investigations

• 👶 Prenatal screening: Combined test (nuchal translucency + maternal serum markers), cell-free DNA testing. Diagnosis confirmed by CVS or amniocentesis.
• 🧪 Postnatal testing: Karyotyping confirms trisomy 21 or translocation.
• 🖥️ Ultrasound findings: Nuchal thickening, cardiac AVSD, “double bubble” duodenal atresia.

🩺 Management

• 🗣️ Developmental support: speech & language therapy, physiotherapy, special education programmes.
• ❤️ Cardiac care: early screening & surgery for congenital defects.
• 🧪 Endocrine & GI monitoring: thyroid screening, coeliac testing, feeding support.
• 👂 Infection prevention & ENT input for recurrent otitis media/hearing loss.
• 🏃 Long-term: obesity prevention, social inclusion, transition to adult services.
• 🎉 Life expectancy has significantly improved - many now live into their 60s+ with good support.

Cases - Down’s Syndrome (Trisomy 21)

• Case 1 - Neonatal features 👶: A newborn girl is noted to have hypotonia, upslanting palpebral fissures, single palmar crease, and sandal gap toes. Echocardiogram shows an atrioventricular septal defect. Karyotype: 47,XY,+21. Diagnosis: Down’s syndrome with congenital heart disease. Managed with supportive neonatal care and surgical planning for cardiac defect.
• Case 2 - Developmental delay & learning disability 🧩: A 5-year-old boy with Down’s syndrome is referred for delayed speech, global developmental delay, and mild intellectual disability. Exam: short stature, macroglossia. Diagnosis: Down’s syndrome with developmental and learning difficulties. Managed with speech therapy, educational support, and regular health surveillance (thyroid, hearing, vision).
• Case 3 - Adult complications ❤️🧠: A 36-year-old woman with Down’s syndrome presents with progressive memory loss and disorientation. Exam: mild cognitive decline and hypothyroidism. Diagnosis: early-onset Alzheimer’s disease in Down’s syndrome. Managed with memory clinic referral, thyroid replacement, and supportive social care.

Teaching Point 🩺: Down’s syndrome (Trisomy 21) is the most common chromosomal abnormality. Key associations: - Neonates: hypotonia, cardiac defects (AVSD, VSD, ASD). - Children: learning disability, recurrent infections, hypothyroidism, hearing/vision problems. - Adults: early-onset Alzheimer’s, sleep apnoea, atlanto-axial instability. Diagnosis confirmed by karyotype or rapid aneuploidy testing. Lifelong multidisciplinary support is essential.