Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Its incidence is approximately 1 in 11,000 live births. In 2007, an International Conference on the Standard of Care for SMA published a consensus statement on SMA standard of care that has been widely used throughout the world. Here we report a two-part update of the topics covered in the previous recommendations. In part 1 we present the methods used to achieve these recommendations, and an update on diagnosis, rehabilitation, orthopedic and spinal management; and nutritional, swallowing and gastrointestinal management. Pulmonary management, acute care, other organ involvement, ethical issues, medications, and the impact of new treatments for SMA are discussed in part 2.

Spinal muscular atrophy (SMA) is a leading inherited cause of infant death with a reported incidence of ∼1 in 10 000 live births and is second to cystic fibrosis as a common, life-shortening autosomal recessive disorder. The American College of Medical Genetics has recommended population carrier screening for SMA, regardless of race or ethnicity, to facilitate informed reproductive options, although other organizations have cited the need for additional large-scale studies before widespread implementation. We report our data from carrier testing (n=72 453) and prenatal diagnosis (n=121) for this condition. Our analysis of large-scale population carrier screening data (n=68 471) demonstrates the technical feasibility of high throughput testing and provides mutation carrier and allele frequencies at a level of accuracy afforded by large data sets. In our United States pan-ethnic population, the calculated a priori carrier frequency of SMA is 1/54 with a detection rate of 91.2%, and the pan-ethnic disease incidence is calculated to be 1/11 000. Carrier frequency and detection rates provided for six major ethnic groups in the United States range from 1/47 and 94.8% in the Caucasian population to 1/72 and 70.5% in the African American population, respectively. This collective experience can be utilized to facilitate accurate pre- and post-test counseling in the settings of carrier screening and prenatal diagnosis for SMA.