BIO 320- CONGENITAL & GENETIC DISORDERS

Teratogen

Any substance or situation that causes a developmental abnormality Viruses Smoking or exposure of mother to second-hand smoke ØChild with low birth weight ØIncreased irritability ØPossible stillbirth Alcohol ØRisk throughout pregnancy ØFetal Alcohol syndrome •Impairs child's neurological and intellectual development Radiation Certain medications, including herbal remedies

Single-Gene Disorders

Autosomal recessive disorders: ØCystic fibrosis ØPhenylketonuria ØSickle cell anemia ØTay-Sachs disease X-linked dominant disorders: ØFragile X syndrome X-linked recessive disorders: ØColor blindness ØDuchenne muscular dystrophy ØHemophilia A

Autosomal Recessive Disorders

Both parents must pass on the allele for disorder. ØParents may be heterozygous and unaffected; they are termed carriers. ØParents may be homozygous and affected. Male and female children are affected equally. Homozygous recessive child has the disorder. Heterozygous child ØNo clinical signs of disease ØChild is a carrier Examples: Cystic fibrosis PKU Tay-Sachs disease

Single-Gene Disorders

Classified by inheritance patterns ØRecessive ØDominant ØX-linked recessive Single gene controls a specific function ØExample: color blindness May have systemic effects ØExamples: cystic fibrosis, Tay-Sachs disease, phenylketonuria (PKU) Examples: Autosomal dominant disorders Adult polycystic kidney disease Huntington's chorea Familial hypercholesterolemia Marfan's syndrome

Gestational Diabetes Mellitus

Develops in 2% to 5% of women May lead to developmental abnormalities if blood glucose level is high in first trimester Newborn is large for gestational age and may experience hypoglycemia after birth Glucose levels should be closely monitored in: ØWomen with family history of diabetes ØPreviously high-birth-weight infants

Autosomal Dominant Disorders

Inheritance of one allele causes disorder; only one parent needs to carry allele No carriers ØUnaffected persons do not transmit the disorder. Some conditions become evident later in life. ØAllele for disorder may have been passed on to next generation before diagnosis of disease in parent. ØTermed delayed lethal genotype Examples: Adult polycystic kidney disease Huntington's disease Familial hypercholesterolemia Marfan's syndrome

X-Linked Disorders: Dominant

Dominant disorder ØHeterozygous males and females affected ØReduced penetrance in females ØFragile X syndrome is an example. •Most common genetic cause of cognitive deficits •Effects are variable and related to the extent of mutation of the allele.

Chromosomal Disorders

Down syndrome: ØTrisomy 21 ØMay be caused by nondisjunction or translocation Turner syndrome XO: ØAffects females ØShort stature ØInfertility Klinefelter syndrome XXY: ØExtra X chromosome is present ØInfertility

Developmental Disorders

Exposure to drugs, chemicals, or radiation during childbearing years TORCH—acronym for maternal infections that can result in anomalies ØRoutine prenatal screening tests Exposure to known teratogens in the first 2 months of development ØImpairs organogenesis

Multifactorial Disorders

Genetic influences combined with environmental factors Examples: ØCleft palate ØCongenital hip dislocation ØCongenital heart disease ØType 2 diabetes mellitus

Pregnancy-Induced Hypertension

Persistently elevated blood pressure Ø>140/90 mm Hg ØDevelops after 20 weeks of gestation ØMay lead to stroke or damage to retina ØReturns to normal after delivery Pre-eclampsia: ØProgressively higher BP ØKidney dysfunction, weight gain, generalized edema ØComplication—HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) Eclampsia: ØExtremely high blood pressure—seizures or coma ØHigh risk of stroke ØMay require cesarean section delivery to reduce maternal risk

X-Linked Disorders: Recessive

Recessive: ØAllele carried on the X chromosome but not the Y chromosome ØManifested in heterozygous males lacking the matching unaffected gene on the Y chromosome ØHeterozygous females are carriers. ØHomozygous recessive females may be affected. ØInheritance may appear to skip generations. ØExamples: •Duchenne muscular dystrophy •Classic hemophilia

Rh Incompatibility

Results when the mother is Rh-negative and the fetus is Rh-positive Usually not a problem during first pregnancy Rh-positive blood enters maternal circulation because of placental tears. Formation of maternal antibodies to Rh-positive blood Subsequent pregnancies—maternal antibodies destroy red blood cells. Hemolysis of red blood cells ØSevere anemia, low hemoglobin ØJaundice may be severe. ØPossible heart failure and death Early delivery or intrauterine transfusion may be recommended. Exchange transfusion after birth may be required

Down Syndrome

Trisomy 21 Common chromosomal disorder ØAffects physical and mental development Risk increases with maternal age Triple or quad screening test and/or first-trimester screening test (ultrasound + maternal blood screening) ØMay be used to screen for risk of Down syndrome ØAmniocentesis or chorionic villi sampling used to confirm the disorder prior to birth

Ectopic Pregnacy

Tubal pregnancy Zygote is implanted outside the uterus ØUsually in the fallopian tubes Spontaneous abortion may follow. Embryo may continue to develop. ØEventually causes tubal rupture ØSevere hemorrhage leading to shock ØDeath ØConsidered a surgical emergency

Genotype

ØActual genetic information carried by the individual ØAll cells except the gametes of an individual have the same genotype. ØNot all genes are expressed in all cells.

Thromboembolism

ØBlood clots, common after childbirth ØUsually develop in veins of legs or pelvis

Thrombophlebitis

ØClot forms over an inflamed area in the vein wall

Phenotype

ØExpression of genes ØAppearance of the individual's characteristics

Embolus

ØIf a piece of the thrombus breaks away: •Will flow with venous blood •May result in a pulmonary embolus

Abruptio Placentae

ØMay occur following motor vehicle accident or spontaneously ØPremature separation of the placenta from the uterine wall, usually causing bleeding ØBlood may be trapped between placenta and uterine wall ØAbdominal pain is common.

Placenta Previa

ØPlacenta is implanted in the lower uterus or over cervical os ØPlacenta may tear at end of pregnancy ØBright red bleeding—painless

Disseminated Intravascular Coagulation

ØSerious complication of other conditions •Examples :abruptio placentae, pre-eclampsia ØIncreased activation of clotting mechanisms •Results in multiple blood clots throughout circulation ØDiagnosis confirmed by low serum levels of clotting factors ØHemorrhage, shock, and tissue ischemia