Ch. 5 Genetic and Congenital Disorders Flashcards
Congenital defects
may be caused by genetics or environmental factors
allele
two members of a gene pair, 1 from mom, 1 from dad
polymorphism
many genes have more than one normal allele at the same locus
codominance
possible for both alleles of a gene pair to be phenotypically seen in a heterozygote
Causes of birth defects
genetic factors: single or multifactorial inheritance or chromosomal aberrations
Environmental factors: maternal disease, infections, or tetragoenics
Intrauterine factors (rare0 fetal crowding, positioning, entanglement of fetal parts with the amnion)
Amnion
inner membrane
Chorion
outer membrane
Single Gene Disorders
may be present on an autosome or x chromosome
may affect one member or both members of an autosomal gene inheritance
-family genetic history
-can be expressed differently in people
-wide variation of gene penetrance
Results of Single Gene disorders
o Formation of an abnormal protein or decreased production of a gene product
o Defective or decreased amounts of an enzyme
o Defects in receptor proteins and their function
o Alterations in nonenzyme proteins
o Mutations resulting in unusual reactions
Disorders of Single Gene Inheritance. Autosomal dominant
Marfan syndrome: connective tissue disorder that is manifested by changes in the skeleton, eyes and CV system. 70-80% are familial inheritance.
Neurofibromatosis: (NF). a condition in which tumors develop from schwann cells of neurologic system. two distinct forms. Type 1 and Type 2.
Autosomal Recessive Disorders
:only when both members of the gene pair are homozygous. both parents may be unaffected but are carriers. characteristically caused by loss of function mutations.
PKU (phenylketonuria) disorder of deficiency of the liver enzyme phenylanaine hydroxylase, (which allows the conversion to tyrosine) allows toxic acid of phenyl to accumulate in tissues and blood.
Tay Sachs Disease: rare, absence of an enzyme that breaks down fatty substances (gangliosides) affects the function of the nerve cell
X linked Recessive
males usually display the phenotype. regardless if dominant or recessive.
sons of of hetero women have 50% of recieving. expression in females is often variable
cause of spontaneous abortions
sex linked disorders are almost always the X chromosome.
Fragile X Syndrome- dominant
chromatin fails to condense during mitosis. second most common cause of mental retardation after downs.
for females, mutant x is dom to normal x. often lethal to embryonic males
affected males will have 100% affected daughters and 100% normal sons
Multifactoral inheritance disorders
caused by multiple genes and environment factors.
ex.Cleft lip or palate. Clubfoot. Congenital dislocation of the hip. Congenital heart disease. Pyloric stenosis .( Vomiting. Hypertrophy of pyloric sphincter. More common in males. Surgically fix. )Urinary tract malformation
Results of Chromosomal disorders
Early gestation loss. congenital malformations. intellectual disabilities.
Aneuploidy
abnormal amount of chromosomes.
Monosomy
presence of only one member of the chromosome pair. (Turner syndrome) monosomy x
Polysomy
presence of more than two chromosomes to a set (Kleinefelter) polysomy x
Down syndrome
excess pair of chromosome.
increased risk with higher maternal age
95% are caused by nondisjunction or an error in cell division during meiosis
Turners Syndrome
only females. one x is missing of partially missing. short height, failure of the ovaries to develop, heart defects
Klinefelter syndrome
too many x chromosomes. male. hypogonadism, decreased body hair, gynecomastia, inc risk for breast cancer, typically tall with long arms and legs. lanky build.
Mitchondrial DNA disorders
subject to mutations at a higher rate than nuclear DNA bc no repair mech.
commonly associated with neuromuscular disorders.
mtDNA) is packaged in a double-stranded circular chromosome and contains 37 genes: 2 ribosomal RNA genes, 22 transfer RNA genes, and 13 structural genes encoding subunits of the mitochondrial respiratory chain enzymes, which participate in oxidative phosphorylation and generation of adenosine triphosphate..always inherited from maternal line
Teratogenic Agents
produce abnormalities during embryonic or fetal development.
radiation. chemical and drugs, infectious agents
Periods of Fetal Development
CNS 3- Full Term Eyes 41/2 to full term Heart 3 ½ to 9 Lower limbs 4 ½ to 9 External Genitalia : 7 to full term Ears 4 ¼ to 20 Teeth 6 ½ to full term Palate 6 ½ to 16 Upper limbs 4 ½ to 9
Pregnancy Categories
old: A-X (d-x has shown injury)
New: 8.1 pregnancy 8.2 lactation 8.3 females and males of reproductive potential
When is a fetus most sensitive to radiation?
2-18 weeks.
FAS
prenatal or postnatal retardation (below 100th percentile) neurologic abnormalities. developmental delays, behaviroal dysfunction, intellectual impairment, skull and brain malformation
Cocaine
decreased blood flow, maternal hypertension, stimulation of uterine contractions, fetal vasoconstriction
Vitamin A derivatives
synthetic retinoids. used to treat acne vulgaris. on BC for up to 3 years after taking regimen. cytotoxic, antimetabolic
Folic Acid deficiency
up to 70% of all deficiencies are preventable.
Spina bifida (lower nerve exposed)
Anencephaly (no brain)
Encephalcocele (brain is outside crainum)
Infectious Agents during pregnancy
TORCH
Toxoplasmosis, other, rubella, cytomegalovirus, herpes
2.5% incidence of these infections in live newborns
Prenatal screening tests
tests can tell you the chance that your fetus has an aneuploidy and a few other disorders
prenatal diagnostic tests:
can tell whether fetus actually has certain disorders. are done on the cells from the fetus or placenta through chorionic villus sampling or amniocentesis
AFP (alpha-fetoprotein)
protein produced by fetus
Estriol
estrogen produced by both the fetus and placenta
Inhibin A
protein produced by the placenta and ovaries
Quad Screen
perfromed between 16 and 18 wks, maternal screen, risk for down syndrome or neural tube defect
cffDNA
present after 5-7 wks, tests for downs, patau syndrome, edwards syndrome, and problems with other sex chromosomes
Edwards syndrome
severe developmental delays due to an extra chormosome 18. low birth weight, small abnormally shaped head, birth defects in organs that are often life threatening. has no treatment and is usually fatal before birth or within the first year of life.
