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Spinal muscular atrophy with lower extremity-predominant (SMA-LED)

Objective: To describe the rare, non-5q SMA, Spinal muscular atrophy with predominant lower extremity (SMA-LED). Methods: A case series of two cases of SMA-LED who presented to pediatric neurology OPD of a tertiary care centre. Case details: Two boys from unrelated families (non-consanguineous, presented with motor developmental delay. There was history of reduced antenatal movements. Perinatal period was uneventful. Both had contractures at birth (CTEV and hamstrings contractures in case 1; CTEV and elbow contractures in case 2). On examination, they were active, smiling, cooing, but paucity of movements, predominantly lower limbs. There was proximal>>distal weakness, areflexia in lower limbs reflexes and preserved reflexes in upper limbs. Both had lower limb-predominant motor axonal neuropathy. MLPA for SMN gene CPK and MRI-LS spine were normal. In the follow up, they had motor>>cognitive and language delay. By late infancy, they had good neck control, could reach for objects and sit with support when made to sit. The lower limb weakness with proximal>distal gradient persisted with mild atrophy of proximal muscles group and contractures. Whole exome sequencing revealed de novo pathogenic heterozygous mutation in DYNC1H1 and BICD-2 genes respectively. Case 1, at 4 years, can stand with braces support and cruises around, and speaks in short sentences and understands 2-3 step commands. Case 2, at 1 year, can sit with support when made to, has monosyllable speech and responds to name call. Conclusion: SMA-LED is unique form of genetic neuropathy with static course and better long-term outcome. Early diagnosis helps in better prognostication.
Keywords: SMA, SMA-LED, Neuropathy, Spinal muscular atrophy