Case Report: Presymptomatic risdiplam in preterm monozygotic twins with co-occurring spinal muscular atrophy and...

Spinal muscular atrophy (SMA) and tuberous sclerosis complex (TSC) are both rare genetic disorders, and their co-occurrence is expected to be exceptionally uncommon. Although risdiplam has demonstrated efficacy in SMA, evidence regarding its use in preterm infants with complex genetic comorbidities remains limited.

We report preterm monozygotic twins born at 32+5 weeks of gestation with genetically confirmed SMA caused by homozygous deletion of SMN1 exons 7-8, with two copies of SMN2. During baseline evaluation prior to presymptomatic treatment, brain magnetic resonance imaging revealed incidental abnormalities, including cortical dysplasia and subependymal nodules, which prompted further genetic testing and led to the diagnosis of TSC with a TSC1 c.1041G>A variant. Presymptomatic risdiplam was initiated at a corrected gestational age of 38+5 weeks. Both twins showed marked improvement in motor function. By 12 months of age, they had achieved independent rolling, unsupported sitting, crawling, and pulling to stand, accompanied by substantial improvements in CHOP INTEND and HINE-2 scores. Risdiplam was well tolerated, and no commonly reported adverse events were observed during follow-up.

This report describes the first documented co-occurrence of SMA and TSC in preterm monozygotic twins and suggests that presymptomatic risdiplam may be effective and well tolerated in this complex clinical setting over 1 year of follow-up. These findings also highlight the importance of comprehensive genetic evaluation in infants with SMA who present with atypical neuroimaging or neurological features. Longer-term follow-up is needed to clarify safety, efficacy, and optimal integrated management strategies in patients with complex genetic comorbidities.