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Prenatal Diagnosis of Genetic Disorders

Genetic disorders have a tremendous potential adverse effect on reproductive-age women and their families. Of conceptuses, 8% (1/13) are chromosomally abnormal, accounting for 50% of all first-trimester abortions and 6-11% of all stillbirths Down syndrome and neonatal deaths. Of all newborns, 34% have a major congenital defect; by age 7 Down's syndrome.

Genetic Disorders

CHROMOSOME ABNORMALITIES

A variety of chromosome abnormalities can occur in association with a live birth. Most autosomal trisomies result from maternal meiotic nondisjunction, a phenomenon that occurs more frequently with advanced maternal age. Numeric sex chromosome abnormalities can result from either maternal or paternal nondisjunction; inversions and translocations may be sporadic or familial.

Trisomy. Most fetal trisomies result from an error in maternal meiosis I. Although any woman at any age can have a trisomic fetus, the frequency of meiotic errors and resulting fetal aneuploidy increases as women (and their eggs) age. Traditionally, women who will be 35 years of age or older at the time of delivery are thought to be at great enough risk that fetal karyotype analysis by CVS or genetic amniocentesis is offered routinely. Women younger than age 35 should be offered prenatal genetic testing if their obstetric history, family history, or maternal serum screening test suggest increased risk.

Sex Chromosome Abnormalities. Sex chromosome abnormalities occur in 1 of every 300-500 births. The most common are 45,X; 47,XXY; 47,XXX; 47,XYY; and mosaicism (the presence of two or more cell populations with different karyotypes). The origin of the chromosome error may be either maternal or paternal in all cases except 47,XYY (in which it is paternal in origin). Women who have had a pregnancy complicated by fetal XXX genetic disorders, prenatal diagnosis, or XXY should be offered prenatal testing in subsequent pregnancies because their recurrence risk for another fetal trisomy is estimated to be 1%.