Detection of Silent Carriers of Spinal Muscular Atrophy: A Survey of Clinical Practice and Recommendations for Screening

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a carrier frequency of approximately 1 in 50, with an estimated 3-9% of carriers being 'silent' (2+0 configuration) and therefore undetectable by standard assays, complicating reproductive genetic counseling and risk assessment. Implementation of Medicare-funded reproductive genetic carrier screening (RGCS; MBS items 73451 and 73452) in Australia in November 2023 has increased the urgency of addressing this diagnostic gap. This study aimed to characterize current practices and perceptions regarding silent SMA carrier detection among genetics professionals in Australia and New Zealand and to identify strategies to improve detection and counseling. A cross-sectional REDCap survey distributed via the Human Genetics Society of Australasia newsletter yielded 62 responses, 95% from Australia and 5% from New Zealand. Genetic counselors comprised 60% of respondents and clinical geneticists 24%. Silent carrier awareness was high (92%), and 53% reported clinical encounters with silent carriers, most commonly identified through family history with affected offspring or through results indicating the presence of high-risk single nucleotide polymorphisms (SNPs) associated with silent carrier status. However, most respondents had counseled fewer than five cases. Management approaches frequently included counseling on residual risk, segregation studies, and prenatal testing. Thematic analysis identified laboratory support limitations, challenging SNP interpretation, counseling complexity, and workforce constraints as major challenges. A model of care was proposed to address these challenges. This study highlights the need for advanced detection methods, workforce education, and development of guidelines for silent carrier management with the increasing uptake and mainstreaming of RGCS.