Theory: Genetics / Chromosomal Disorders
1. Chromosomal Aneuploidy
Aneuploidy: abnormal chromosome number (not exact multiple of haploid set). Trisomy (+1): 2n+1 = 47. Monosomy (−1): 2n−1 = 45. Cause: non-disjunction (failure of chromosome pair to separate) during meiosis I or II (or mitosis → mosaic aneuploidy). Common trisomies: Trisomy 21 (Down), Trisomy 18 (Edwards), Trisomy 13 (Patau). Common sex chromosome aneuploidy: Turner (45,X), Klinefelter (47,XXY), Triple X (47,XXX).
2. Key Chromosomal Disorders Summary
Disorder — Karyotype — Chromosome count — Key feature: Down — 47,+21 — 47 — Intellectual disability, trisomy 21. Edwards — 47,+18 — 47 — Severe, clenched fists. Patau — 47,+13 — 47 — Cleft lip, polydactyly. Turner — 45,X — 45 — Short female, infertile. Klinefelter — 47,XXY — 47 — Tall male, infertile. Triple X — 47,XXX — 47 — Tall female, fertile. Jacob — 47,XYY — 47 — Tall male.
3. Non-Disjunction
Non-disjunction in meiosis I: homologous chromosomes fail to separate → both go to same cell → after meiosis II, two cells have 24 chromosomes, two have 22. Non-disjunction in meiosis II: sister chromatids fail to separate → one cell has 24, one has 22, two normal. Maternal age effect: risk of non-disjunction increases with age (aged oocytes, prolonged arrest in meiosis I prophase, degraded cohesin proteins that hold chromosomes together).
4. Prenatal Diagnosis
Prenatal testing for chromosomal disorders: Non-invasive: ultrasound (nuchal translucency, structural anomalies), cell-free fetal DNA (NIPT/NIPS) in maternal blood — screens for common trisomies from 10 weeks. Invasive (confirmatory): amniocentesis (15-20 weeks, amniotic fluid → fetal cells → karyotype/FISH/array CGH), chorionic villus sampling (CVS, 10-13 weeks, placental cells). Preimplantation genetic testing (PGT): test embryos before IVF transfer.
Frequently Asked Questions
1. What is Down syndrome? ⌄
Down syndrome (Trisomy 21): extra copy of chromosome 21. Karyotype: 47,XX,+21 (female) or 47,XY,+21 (male). Total chromosomes = 47. Cause: non-disjunction during meiosis (most commonly in maternal meiosis I; risk increases with maternal age). Features: intellectual disability, characteristic facial features (epicanthal folds, flat nasal bridge, protruding tongue), hypotonia, congenital heart defects, increased risk of Alzheimer's disease. Life expectancy has improved to 50-60 years with modern care.
2. What is Turner syndrome? ⌄
Turner syndrome (Monosomy X): missing one X chromosome. Karyotype: 45,X (or 45,X0). Total chromosomes = 45 (ONE fewer than normal 46). Phenotype: FEMALE (no Y chromosome). Features: short stature, streak ovaries (non-functional, premature ovarian failure), infertility, webbed neck, shield chest, lymphoedema at birth, coarctation of aorta. Intelligence usually normal. Treatment: oestrogen replacement at puberty (develop secondary sexual characteristics), growth hormone therapy.
3. What is Trisomy 18 (Edwards syndrome)? ⌄
Edwards syndrome (Trisomy 18): extra chromosome 18. Karyotype: 47,+18. More severe than Down syndrome. Features: severe intellectual disability, heart defects (ventricular septal defect), overlapping fingers, rocker-bottom feet. Most pregnancies end in miscarriage; 90% of liveborn infants die within first year. Second most common autosomal trisomy after Down syndrome.
4. What is Klinefelter syndrome? ⌄
Klinefelter syndrome: extra X chromosome in males. Karyotype: 47,XXY. Total chromosomes = 47. Phenotype: MALE (Y chromosome present). Features: tall stature, small testes (hypogonadism), gynecomastia (breast development), infertility (azoospermia), may have mild learning difficulties. Testosterone replacement therapy used.
5. What are other chromosomal disorders? ⌄
Trisomy 13 (Patau syndrome): severe intellectual disability, cleft lip/palate, polydactyly, heart defects. Most die within first year. Triple X syndrome (47,XXX): karyotype 47,XXX, female, usually fertile, mild learning difficulties or no phenotype. Jacob syndrome (47,XYY): tall male, fertile, often no distinctive phenotype. Cri-du-chat (5p deletion): high-pitched cry, intellectual disability. Prader-Willi/Angelman: imprinting disorders of chromosome 15.