Down Syndrome Diagnosis and Characteristics

Down Syndrome

• Cell cycle is arrested at metaphase, and chromatids are purified, Giemsa stained, and analyzed for number and rearrangements.
• Symptoms include low muscle tone, single deep crease across the center of the palm, looseness of joints, small skin folds at the inner corners of the eyes, and excessive space between the first and second toe.
• Mental retardation is always present, ranging from mild to severe, with most cases being mild to moderate.

Trisomies

• Patau Syndrome (Trisomy 13): characterized by polydactyly, deformed/rocker-bottom feet, neurological problems, facial defects, and cardiac/renal defects.
• Edwards Syndrome (Trisomy 18): characterized by low birth weight, prominent occiput, clubbed hands, neurological problems, facial defects, and cardiac/renal malformations.

Klinefelter's Syndrome

• Results from nondisjunction of the 21st chromosome (Trisomy 21), leading to characteristic facial and body patterns, and varying mental abilities.
• Occurs when a sperm containing both X and Y combines with an egg containing the X, resulting in a male child with an extra X chromosome.
• Leads to sterile males with female characteristics.

Genetic Variation

• Three mechanisms contribute to chromosomal genetic variation: independent assortment of chromosomes, crossing over, and random fertilization.
• Independent assortment reshuffles alleles and chromosomes every generation, resulting in 2^n possible combinations (8,388,608 for humans).
• Random fertilization leads to 70 trillion possible offspring (excluding cross over).
• Mosaicism, the presence of 2 or more genetically different sets of cells, can affect the expression of genetic disorders.

Mosaicism

• All females are mosaics due to X-chromosome inactivation (lyonization).
• Can be caused by a mitotic error soon after fertilization.
• 5% of Down Syndrome patients are a mosaic variant, with only some cells having a trisomy 21.

Independent Assortment

• With n=2, there are 4 possibilities (A and a, B and b, C and c) and 8 possible combinations.
• The "2" rule states that the number of possible chromosome sorting combinations is 2^n.

Cross Over

• A single crossing over event leads to 4 genetically unique daughter cells.
• Crossing over occurs during Meiosis I, resulting in recombinant chromosomes.

When Things Go Wrong

• Aneuploidy: any deviation from the normal number of chromosomes, usually meaning a cell nucleus possessing too many or too few chromosomes.
• Somatic aneuploidy: non-heritable and has a localized effect.
• Meiosis can lead to trisomy, monosomy, or tetrasomy.

Karyotype

• XXY (Klinefelter's Syndrome): males with some development of breast tissue, little body hair, and small testes, leading to infertility and possible mental retardation.
• Turner Syndrome (XO): sterile females with webbed necks, shortened torso, and a range of physical and developmental abnormalities, affecting 1 in 2,000 live births.