Classic Case

Mutations in the LAMA2 gene cause severe neonatal congenital myasthenia dystrophy and occasionally give rise to a limb-girdle muscular dystrophy–like syndrome. Patients usually present with delayed motor milestones, a limb-girdle pattern of weakness, raised creatine kinase values, epilepsy, and leukoencephalopathy. Independent ambulation is achieved in this group of patients. Characteristic symmetric hyperintense T2 signal in the periventricular and subcortical white matter is observed in most patients. U-fibers are relatively spared (A and B, arrows). Two compound heterozygous mutations (c.437C>a(p.S146Y), c7263delA) were identified in this case. The combination of a white matter lesion and myopathy is uncommon. Differentials include myotonic dystrophy and MNGIE. The former presents with prominent myotonia. The latter presents with gastrointestinal dysmotility, ptosis, ophthalmoplegia, and hearing loss.