Genetic Disorders
Down Syndrome (Trisomy 21)
다운증후군
Most common chromosomal disorder caused by trisomy of chromosome 21
- How common
- 1 in 700 live births
- Typical age
- Lifelong from birth
What is it?
Three copies of chromosome 21 (47,XX,+21 or 47,XY,+21); 95% from meiotic nondisjunction.
Commonly affected: Systemic (heart, brain, GI, thyroid, blood)
How it develops
- Meiotic nondisjunctionMaternal meiosis I nondisjunction (maternal-age effect)
- Chromosome 21 over-expressionDSCR genes (APP, SOD1, DYRK1A) overdose
- Developmental abnormalityAV septal defect, neural delay, hypotonia
- Clinical manifestationDysmorphism + ID + CHD + early-onset Alzheimer
Symptoms
- Congenital heart disease40–50% have AVSD, VSD, or ASD
- Facial featuresFlat nasal bridge, low-set ears, upslanted palpebrae, epicanthal folds
- HypotoniaFloppy baby from neonatal period
- Intellectual disabilityMild-moderate ID, IQ 35–70
- Single palmar creaseSimian crease, sandal gap toe
How it is examined
- Newborn examDysmorphic features + hypotonia + murmur
- EchocardiogramScreen for AVSD/VSD (all infants)
- Karyotype (confirmatory)Peripheral blood G-banding or FISH
Imaging
CXR + echocardiography to evaluate AV septal defect.
- Cardiomegaly
- Increased pulmonary vasculature
Cervical spine films for atlantoaxial instability.
- Atlantoaxial instability (15%)
- Single palmar crease
Non-surgical care
- Early interventionPT, OT, speech therapy (start <3 months)
- Thyroid screeningNewborn, 6 months, yearly (congenital hypothyroidism common)
- Hearing/vision screenFrequent hearing loss and cataracts → yearly screen
- Leukemia surveillance10–20× increased TMD/AMKL risk
- Educational supportSpecial education with individualized IEP
Conservative options are generally tried first. Medications listed here can have side effects — discuss them with your prescriber.
When surgery is considered
Congenital heart defect (AVSD/VSD)
Procedures that may be discussed
- Cardiac repair within 3–6 months
- Cataract removal
- Tympanostomy tubes (chronic OM)
Outlook
Life expectancy now ~60 years. Cardiac repair + early intervention dramatically improve QoL.