Spinal muscular atrophy genetic epidemiology and the case for premarital genomic screening in Arab populations

Abstract

Abstract Background Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence has not been well-characterized in most Arab countries where rates of consanguinity are high. Understanding SMA disease epidemiology has important implications for screening, prevention, and treatment in those populations. Methods We perform SMA diagnostic testing in a clinical multi-national patient cohort (N = 171) referred for hypotonia and/or muscle weakness. In addition, we carry out genetic newborn screening for SMA on 1502 healthy Emirati newborns to estimate the carrier frequency and incidence of the disease in the United Arab Emirates. Results Patients referred for SMA genetic testing are mostly Arabs (82%) representing 18 countries. The overall diagnostic yield is 33.9%, which is higher (>50%) for certain nationalities. Most patients (71%) has two SMN2 copies and earlier disease onset. For the first time, we estimate SMA carrier frequency (1.3%) and incidence of the disease (1 in 7122 live births) in the United Arab Emirates. Using birth and marriage rates in two Arab populations (United Arab Emirates and Saudi Arabia), as well as disease incidence in both countries, we show that, besides preventing new cases, premarital genetic screening could potentially result in around $8 to $324 million annual cost savings, respectively, relative to postnatal treatment. Conclusions The SMA carrier frequency and incidence we document suggests high potential benefit for universal implementation of premarital genomic screening for a wide range of recessive disorders in Arab populations.