Spinal Muscular Atrophy with Predominant Lower Extremity (SMA-LED) with Intellectual Disability and Dysmorphism

Excerpt

To the Editor: DYNC1H1-related diseases have variable phenotypes, affecting the function of either the central or peripheral nervous system or sometimes both. Spinal muscular atrophy with predominant lower extremity (SMA-LED) is an autosomal dominant disease characterized by non-progressive early onset lower limb predominant weakness and wasting, mostly due to variants of the tail domain of the DYNC1H1 gene [1‐4]. We present a case of 10-y-old girl with SMA-LED. Patient presented with a history of lower limb weakness noticed since early infancy. Childbirth was uneventful. The child had a history of global development delay. The patient had facial dysmorphism (Supplementary Fig. S1) and significant lower limb weakness and wasting of distal muscles of the foot. Power in the lower limb muscles was 3/5. Deep tendon reflexes were absent in the lower limbs. There was no upper limb or facial muscle weakness. The patient had a positive Gowers sign (Supplementary Fig. S1). The patient's creatinine phosphokinase (CK) enzyme level was 167 U/L. Brain magnetic resonance imaging (MRI) was suggestive of dilated ventricles (Supplementary Fig. S1). On electromyography (EMG), there were signs of chronic denervation. With physical examination and electrodiagnostic findings, the possibility of type 3 SMA was kept. MLPA for SMN1 was negative. Whole-exome sequence analysis revealed a pathogenic heterozygous missense mutation c.9142G > A (p. Glu3048Lys) detected in the DYNC1H1 gene in exon 47. …