Newborn and Carrier Screening for Spinal Muscular Atrophy

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that occurs in about 1 in 10,000 live births. SMA is caused by mutations in the survival motor neuron (SMN1) gene; homozygous deletion of exon 7 of the SMN1 gene has been observed in the majority of patients with SMA. A reliable and sensitive SMA diagnostic test is available that can identify this specific deletion in about 95% of the SMA affected patients. No specific therapy for SMA is currently available, although several promising therapies are being investigated. Early identification of affected infants before presentation of clinical symptoms may permit their enrollment in a clinical trial and the start of potential proactive treatment before the occurrence of irreversible neuronal loss and damage, usually within 3 to 6 months of delivery. The primary goal of population-based screening of newborn infants for SMA is to identify cases early, before symptoms occur, so that appropriate care can be provided. The purpose of population screening of potential parents is to identify at-risk couples, so that they can undergo genetic counseling and prenatal diagnosis, and can thus make an informed reproductive choice. At present, neither newborn screening nor carrier screening is considered standard of care. In this study, 2 pilot projects were performed addressing the clinical applicability of both population-based newborn screening and carrier screening. Newborn screening was performed on 40,103 anonymized blood spots, and 4 cases of SMA were correctly identified. Carrier screening was performed on 500 preconception or pregnant women, and 16 carriers were identified. A survey was sent to potential participants and responses were received from 392 patients of whom, 229 accepted prenatal carrier screening. After learning of their test results, the vast majority (98.7%) were glad they pursued screening. The findings of this study demonstrate that both population-based newborn screening and carrier screening for SMA is technically feasible and can provide an estimate of carrier frequency. The study also provides an assessment of the educational material used during genetic counseling that helps individuals to make an informed decision regarding carrier testing.