Chromosomal Disorders Flashcards
Down Syndrome
-extra 21st chromosome
- Craniofacial (eye folds, protruding tongue, upward palpebral fissure)
- Limbs (single palm crease, gap b/n toes 1 and 2)
- Heart (patent ductus arteriosus, atrial and ventricular defects)
- Short stature + inc risk of AD and leukemia
- Hypotonia
Patau Syndrome
- extra 13th chromosome
- Bilateral cleft lip, microcephaly, extra digits, heart probs
- 98% die in utero
Edwards Syndrome
- extra 18th chromosome
- Triangular face w/ palpebral fissures, hands in fists, rocker bottom feet, sometimes organs in sac outside body + other holes in GI tract, valve probs
- 95% die in utero
Why is there variation in severity of these chromosomal disorders?
Possibly…
- mosaicism
- some may methylate extra chromosome
- alt gene expression
Cri Du Chat
-Deletion in part of chromosome 5 (most are spontaneous mutations)
- Distinguishing feature= high pitch cat cry (malformed larynx)
- Dev delay, microcephaly, low birth weight, hypotonia, heart defects, facial features
Wolf-Hirschhorn Syndrome
-Deletion in pat of chromosome 4 (most are spontaneous mutation)
- Greek warrior helmet (broad flat face w/ flat nasal bridge and high forehead
- Intellectual disability, delayed growth, seizures
PAR 1 and PAR 2
- “Pseudoautosomal regions”
- Homologous regions on X and Y chromosomes that undergo homologous recombination between X and Y in meiosis
- Crossover in PAR 1 is needed to get proper segregation of chromosomes in males
X v Y chromosome
X- larger, functions beyond sex (so abnormal X chromosome can lead to non-sexual disorders and conditions)
Y- smaller, mainly involved in spermatogenesis and sex determination (contains SRY gene)
SRY
- Testes Determining Factor
- On Y chromosome (PAR 1)
- Active early in dev (week 6) to cause undifferentiated gonads to become testes in males (if no SRY –> gonads become ovaries) **testes, seminferous and leydig cells
- Testes then secrete androgens –> secondary sex characteristics
How does X inactivation work?
- all but 1 X chromosome is inactivated in females (to avoid gene dosage problems)
- Inactive X chromsome = Barr Bodies
- 50/50 random whether paternal or maternal X is inactivated
- Governed by XIC (X inactivation center)
- Xinact - transcribes XIST - which coats Xinact to maintain inactivation and turn it into a Barr Body
- X act - transcribes TSix - can inactivate XIST and XIC (so that this X stays ACTIVE)
TSix v. XIST
- XIST = made by inactive X chromosome to stay inactive; RNA but not translated (mainly repeats)
- TSix = made by active X chromosome; opposite strand of XIST gene (antisense RNA)
Turner Syndrome
X,O (only 1 X chromosome)
- 98% spontaneously abort
- May notice at birth (face, short stature, widely spaced nipples, webbed neck)
- Or notice as adult b/c infertile (ovaries degenerate)
- Also renal and heart probs BUT usually normal intelligence
- 70% lack paternal X
- 25% are mosaic
Triple X
XXX (females)
-No phenotypic abnormalities so usually go undiagnosed BUT may have mild mental probs
-Fertile w/ normal kids
(**probably b/c extra X is also inactivated)
XXXX/XXXXX
-Very rare but more symptoms than XXX (inc intellectual disability, facial dysmorphism)
Kleinfelter Syndrome
- XXY (males)
- Problem in either paternal or maternal meiosis
- Usually not diagnosed until puberty (small testes, INFERTILE)
- Androgen def –> dec muscle tone/libido/bone mineralization
- Breast swelling + inc breast cancer risk
- Tall (long limbs)
