Human Genetic Disorders - Chromosomal Disorders or Abnormalities

Chromosomal disorders arise from changes in the number or structure of chromosomes, rather than mutations in individual genes. They are classified into Numerical Abnormalities (change in chromosome count) and Structural Abnormalities (change in chromosome architecture). Both types are caused either by errors during cell division or by exposure to mutagenic agents.

1. Down's Syndrome (Trisomy 21)

• Karyotype: 47, +21 (extra chromosome 21); also written as 44A + 2sex chromosomes + 1 extra chromosome at 21​
• Incidence: 1 in 660–700 live births — most common autosomal aneuploidy​
• Cause: Nondisjunction during oogenesis (maternal nondisjunction in ~95% cases); risk increases with maternal age​

Clinical Features:

• Short stature, broad hands with short fingers
• Flat facial profile with broad skull and flat nasal bridge
• Epicanthal folds (skin fold at inner corner of eye)
• Large, furrowed tongue; open mouth appearance
• Intellectual disability (mild to moderate)
• Congenital heart defects (present in ~50% of cases)
• Increased risk of acute leukaemia and Alzheimer's disease

2. Patau Syndrome (Trisomy 13):

• Karyotype: 47, +13 (extra chromosome 13)​
• Incidence: 1 in 5,000 live births​

Clinical Features:

• Severe intellectual disability
• Congenital heart defects
• Extra fingers (polydactyly)
• Cleft palate and lip
• Small eyes (microphthalmia) or absent eyes (anophthalmia)
• Most affected infants die within the first year of life

3. Edwards Syndrome (Trisomy 18):

• Karyotype: 47, +18 (extra chromosome 18)​
• Incidence: Second most common trisomy in live births​

Clinical Features:

• Severe intellectual disability
• Characteristic "rocker-bottom" feet
• Overlapping fingers with clenched fists
• Congenital heart, kidney, and lung defects
• Very high neonatal mortality; most survive less than 1 year

1. Klinefelter's Syndrome (47, XXY):

• Karyotype: 47, XXY - extra X chromosome in genetic males​
• Gender: Affects males only
• Incidence: ~1 in 650 male newborns - most common sex chromosome disorder​
• Cause: Nondisjunction in Meiosis I or II during gametogenesis in either parent​

Clinical Features:

• Tall stature with long limbs
• Small, underdeveloped testes (hypogonadism/micro-orchidism)
• Gynecomastia (breast tissue development) in late puberty
• Sparse body and facial hair
• Infertility (azoospermia/oligospermia) — most common cause of male hypogonadism
• Mild intellectual or learning difficulties in some patients
• Elevated urinary gonadotropin levels

2. Turner's Syndrome (45, XO):

• Karyotype: 45, XO (monosomy X) - only one functional X chromosome
• Gender: Affects females only
• Incidence: ~1 in 2,000–2,500 live female births
• Cause: Nondisjunction resulting in loss of one sex chromosome; missing chromosome is usually the paternal X in ~2/3 of cases​

Clinical Features:

• Short stature (average adult height ~145 cm)
• Webbed neck (pterygium colli)
• Broad chest with widely spaced nipples
• Rudimentary / streak ovaries → absent secondary sexual characteristics
• Primary amenorrhoea (no menstruation)
• Infertility (primary ovarian insufficiency)
• Normal intelligence in most cases
• Risk of cardiac abnormalities (coarctation of aorta)

3. Triple X Syndrome (47, XXX):

• Karyotype: 47, XXX - extra X chromosome in females​
• Incidence: ~1 in 1,000 female newborns​

Features: Usually phenotypically normal females; taller than average; mild learning difficulties possible; often fertile

4. XYY Syndrome (47, XYY):

• Karyotype: 47, XYY - extra Y chromosome in males​
• Incidence: ~1 in 1,000 male newborns​

Features: Phenotypically normal males; tall stature; fertile in most cases; associated with behavioural tendencies in older literature (no longer considered clinically significant)

• Increase in the number of entire chromosome sets (3n, 4n, 6n…)​
• Examples: Triploid (3n), Tetraploid (4n)
• In Plants: Very common - wheat (Triticum) is hexaploid (6n = 42); banana is triploid (3n); polyploid crops often show increased size and vigour​
• In Animals: Generally lethal - very rare in mammals as dosage compensation mechanisms cannot accommodate multiple X chromosomes

Structural chromosomal abnormalities arise when a chromosome segment breaks and rejoins abnormally. This may occur spontaneously or be induced by radiation, chemicals, or viruses.

Types of Structural Abnormalities: