​PRENATAL DIAGNOSIS OF SPINAL MUSCULAR ATROPHY IN HIGH-RISK FAMILIES

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder caused predominantly by homozygous deletions of exon 7 of the SMN1 gene. Families with a previously affected child face a 25% recurrence risk in each pregnancy, making prenatal genetic testing a key strategy for early detection, clinical decision-making, and disease prevention.
Two unrelated non-consanguineous couples with a history of SMA underwent medical genetic counseling and invasive prenatal diagnostics (IPD) in subsequent pregnancies. Molecular testing included MLPA copy-number analysis of SMN1 and SMN2 exons 7 and 8. When clinically indicated, targeted molecular testing for additional monogenic disorders and cytogenetic analysis were also performed.
Case 1: A couple with one child affected by SMA type 1 and another with autosomal dominant congenital myotonia underwent invasive prenatal diagnosis at 13+2 weeks due to high biochemical risk and confirmed SMA carrier status. Prenatal testing excluded SMA (two SMN1 exon 7/8 copies) and the familial CLCN1 variant; pregnancy continued. Case 2: Both parents, confirmed SMN1 exon 7 carriers after the death of their first child from SMA type 1, underwent IPD at 11 weeks in a subsequent pregnancy. A homozygous SMN1 exon 7 deletion confirmed fetal SMA, and the pregnancy was terminated following counseling.
These cases highlight the critical role of invasive prenatal testing in the early detection and prevention of SMA. Prenatal molecular diagnosis enables informed reproductive choices and reduces the recurrence of severe neuromuscular disease in high-risk families. This research has been funded by the Program targeted funding (No. BR27199879).