located on the long arm of chromosome 5 (5q 13.2) and encodes the SMN protein. Types I and II account for 80 percent of cases and are both lethal (American College of Obstetricians and Gynecologists, 2017b). SMA type I, known as WerdnigHofmann, is the most severe. Disease onset is within the first 6 months, and afected children die of respiratory failure by age 2 years. Type II generally has onset before age 2 years, and the age at death can range from 2 years to the third decade of life. Type III also presents before age 2 years, with disease severity that is milder and more variable. Type IV does not present until adulthood.
The American College of Obstetricians and Gynecologists (20 17b) recommends that carrier screening for SMA be ofered to all women who are considering pregnancy or are currently pregnant. The SMA carrier frequency approximates 1:35 in those of non-Hispanic white (caucasian) ethnicity, 1:41 in Ashkenazi Jews, 1:53 in Asians, 1:66 in African Americans, and 1: 117 in those of Hispanic white ethnicity (Hendrickson, 2009). Carrier detection rates range from 90 to 95 percent for each race/ethnicity except African Americans, in whom it just exceeds 70 percent. Approximately 2 percent of individuals with SMNI mutations are not identiied with carrier screening. In addition, although there is usually one copy of the SMNI gene on each chromosome, approximately 3 to 4 percent of individuals have two copies of this gene on one chromosome and no copies on the other. These individuals are carriers for the disease. African mericans are more likely to have this genetic variation, which explains the lower sensitivity of screening in this group. he American College of Obstetricians and Gynecologists (20 17b) recommends that prior to screening for SMA, providers counsel about its potential spectrum of severity, carrier frequency, and its detection rate. Posttest counseling should include the residual risk after a negative screening result, which difers according to the patient's ethnicity and also according to the number of SMNI copies detected. Most unafected individuals have two copies, but a small percentage has three copies and is at even lower risk. If the patient or her partner has a family history of SMA, or if carrier screening is positive, genetic counseling is recommended.
These include sickle-cell anemia, sickle-cell hemoglobin C disease, and sickle-cell 3-thalassemia. Their pathophysiology and inheritance are discussed in detail in Chapter 56 (p. 1081).
African and African-American patients are at increased risk to carry hemoglobin S and other hemoglobinopathies and should be ofered preconceptional or prenatal screening. Of African Americans, 1 in 12 has sickle-cell trait, 1 in 40 carries hemoglobin C, and 1 in 40 carries the trait for 3-thalassemia. Hemoglobin S is also more common among individuals of
Middle Eastern, and Asian Indian descent (Davies, 2000). The American College of Obstetricians and Gynecologists (2015) recommends that patients of African descent be ofered hemoglobin electrophoresis. If a couple is at risk to have a child with a sickle hemoglobinopathy, genetic counseling should be ofered. Prenatal diagnosis can be performed with either chorionic villus sampling or amniocentesis.