Genetic and Chromosomal disorders

gene mutation

biochemical events that produces a new allele for a particular gene

single gene disorder

cause by defective or mutant allel at a single gene locus
usually obtained through famiy genetic hx

common single gene mutations

cystic fibrosis, sickle cell, tay-sachs, hemophilia A, marfan

autosomal dominant disorders

single mutant passed on regardless of gender

sex linked disorders

almost always are associated with the x chromosome—predominantly recessive

inherited multifactoral disorders

caused by influence of multiple genes along w/ environmental factors

examples of inherited multifactorial disorders

cleft lift, club foot, urinary tract malformation

study of chromosomal disorders

cytogenetics

autosomal recessive disorder

only manifest when both members of gene pairs are affected (homozygous)

margain of safety

ensures that cells with half their usual amount of exzyme function normally

2 examples of autosomal recessive disorders

PKU and Tay-sachs

aneuploidy

abnormal number of chromosomes

monosomy

presence of only one member of a chromosome pair

polysomy

more than two chromosomes to a set

Down syndrome

most are caused by error in cell division during meiosis—trisomy of chromosome 21

features of down syndrome

small square head, flat facial profile, small nose and depressed nasal bridge, slanting eyes, open mouth, large tongue

turner syndrome

absence of all or part of the x chromosome

short in stature, normal body proportions

do not menstruate, no signs of secondary sex characteristics

tx: estrogen therapy. growth hormone therapy.

Klinefelter syndrome

testicular dysgenesis—one or more extra x chromosome in excess of normal xy

enlarged breasts, sparse facial and body hair, small testes, inability to produce sperm

mitochondrial gene disorders

mitochondrial DNA (mtDNA) mutations/rearrangements

mtDNA inherited from

mother’s side only

organogenesis

day 15-60 after conception

teratogenic agents

chemical, physical, or biologic that produce abnormalities during embryonic or fetal development

how do teratogenic agents impact development?

1. direct exposure to agent

2. slow clearance rate for a soon to be pregnant woman

3. mutagenic effectts—occurs before pregancy and damage reproductive cells

most common radiation effects

microcephaly, skeletal malformations, and mental retardation

environmental teratogen

mercury (by contaminated water, fish)

pharmacological teratogen

thalidomide, warfarin, anticonvulsant drugs, vitamin A (accutane)

FDA pregnancy drugs

A, B, C, D, X—A is least dangerous, X are contraindicated

FAS (fetal alcohol syndrome) effects

CNS involvement, behavioral dysfuction, eye opening, elongated, flat midface and groove above lip

TORCH

microorganisms cross placenta causes malformation

Toxoplasmosis,
Other

Rubella

Cytomegalovirus

Herpes

Folic acid deficiency

neural tube defects

tx: folic acide long term by women of reproductive age

diagnostics for genetic and congential disorder

prenatal screening, ultrasound, serum markers, amniocentesis, chorionic villus sampling, percutaneous umbilical cord blood sample, cytogenetic and DNA analyses

ultrasound diagnosis

cardiac defects, hydrocephalus, spina bifida, facial defects, congestial heart defects, congenital diaphragmatic hernias, GI, skeletal

serum markers in pregnancy

first trimester, usually between 11-13weeks

quad screen

used to detect down syndrome

quad screen

AFP, hCG, estriol, inhibin A

amniocentesis

invasive diagnostic procedure

sample of amniotic fluid

elevated risk on first trimester screening

can be done as early as 15 weeks