HCR 240: Genetic Diseases - Chromosome Abnormalities

What is polyploidy

cells with 3 or more copies of each chromosome; fetuses do not survive (stillborn or miscarriage)

What is aneuploidy

cells with an abnormal number of one particular chromosome, typically a result of nondisjunction
- down syndrome (trisomy 21), trisomy X (47, XXX), Turner syndrome (45, X), Klinefelter syndrome (47, XXY)

What is down syndrome

- trisomy 21
- occurs 1 in 800 live births
- incidents of disorder increases with maternal and paternal age (older than 35 increases probability)

What is the increased risk and life expectancy of down syndrome

- has an increased risk of congenital heart defects, respiratory infections, leukemia, and Alzheimer disease
- life expectancy is around 60 years

What are down syndrome characteristics

intellectual disabilities
- low nasal bridge
- epicanthal folds (mono lid)
- protruding tongue
- flat and low-set ears
- short stature
- poor muscle tone

What is turner syndrome

- sex-linked aneuploidy → every child is female genotype
- females have only 1 X chromosomes (instead of normal 2 chromosomes)
- denoted as karyotype 45, X

What are manifestations for turner syndrome

absence of ovaries (sterile), short stature, webbing of the neck, widely spaced nipples, high rates of fetal mortality

How often does turner syndrome occur and what do patients receive with turner syndrome

- occurs 1 in 2500 female births
- teenagers receive estrogen replacement therapy to promote secondary sexual characteristics

What is trisomy X

- sex-linked aneuploidy
- 1 in 1000 female births
- females have 3 or more X chromosomes

What are symptoms of trisomy X and diagnosis for it

- symptoms are variable and include sterility, menstrual irregularity, and/or cognitive deficits
- may not be diagnosed until later in life (typically have worsening symptoms with additional X chromosomes)

What is klinefelter syndrome

- sex-linked aneuploidy
- 1 in 1000 male births
- at least 1 Y and 2 or more X chromosomes

What are the characteristics of Klinefelter syndrome

- overall male appearance, gynecomastia (unintentional breast tissue development in males), small testes, sparse body hair
- many have extra Y chromosomes (typically have worsening symptoms with additional X chromosomes

Describe Klinefelter syndrome in regards to genotype and phenotype

male genotype with female characteristics

What is fragile X syndrome

- site is on the long arm of X chromosome and has elevated number of repeated DNA sequences (CGG)
- manifestations: intellectual disabilities, behavioral problems, long and narrow faces, large protruding ears, hyper-extensible finger joints
- second most common cause of intellectual disability after down syndrome

Describe fragile X syndrome in regards to chromosomes and in female vs male patients

normal amount of chromosomes but the X chromosome is too long. It gets so long that the body doesn’t make the gene.
- female patients have mild symptoms due to 2 X chromosomes
- male patients have more severe symptoms due to only 1 X chromosomes