Medical Genetics Health Article

MULTIFACTORIAL DISORDERS

Neural Tube Defects. Neural tube defects (NTDs) are the disorders most commonly screened for prenatally. The incidence of NTDs is between 1 in 1,000 and 2 in 1,000 births. A family history of NTDs and diabetes in the mother increases the risk significantly. If the mother's diet is supplemented with folic acid before conception, however, the incidence of NTDs decreases. These defects are associated with high mortality, high morbidity, and long-term developmental disability. They involve structural abnormalities of the spine, spinal cord, head, and brain.

In the United States, of every 1,000 pregnant females who are tested between 16 and 18 weeks' gestation, about 25 to 50 will have increased levels of maternal serum alpha-fetoprotein (msAFP) and 40 to 50 have low levels. The mothers with high levels of msAFP can undergo ultrasonography to assess gestational age, the presence of a multiple gestation, or significant abnormality. An alternative is to repeat the test within one to two weeks for mothers with abnormally high or low levels of the protein. If the repeat studies confirm the previous abnormal results, ultrasonography is then performed. After screening with ultrasonography, about 17 of the patients with increased levels of msAFP and 20 to 30 with low levels will have no findings that explain the abnormal values. Amniocentesis should be performed in these patients. Of the 17 patients with high levels, 1 or 2 will have a fetus with a significant NTD, whereas 1 in 65 of those with a low msAFP will have a fetus with a chromosome abnormality (1 in 90 chance of Down syndrome). For a pregnant female with an abnormally high msAFP level and a fetus with no NTD, the risk of stillbirth, low birth weight, neonatal death, and congenital anomalies is increased.

Other Disorders. The overall risk for recurrent cleft lip, with or without cleft palate, is 4 percent if a sibling or parent has the abnormality and 10 percent if it is present in two previous siblings. Lip pits or depressions on the lower lip of a newborn may be the manifestation of an autosomal dominant trait, and the recurrence rate for a sibling is 50 percent.

Generally, the incidence of multifactorial congenital disorders is less than 5 percent. The incidence of recurrence is 2 to 5 percent for cardiac anomalies, 1 to 2 percent for tracheoesophageal fistula, 1 to 2 percent for diaphragmatic hernia, 6 to 10 percent for hypospadias, and 4 to 8 percent for hip dislocation.