P.3.10 An unusual double trouble of coexisting distal myopathy and distal motor neuropathy uncovered by exome sequencing

Distal muscle weakness and atrophy is the presenting symptom of both distal myopathies and distal motor neuropathies. Differential diagnosis might be complicated by the coexistence of secondary axonal changes in primary distal myopathies, or the identification of unspecific myopathic changes on muscle biopsies in neuropathies. We report a two generations Caucasian family with at least 3 affected family members presenting with distal weakness and pes cavus in the teens. The index case was referred to us at the age of 14 years, due to Achilles tendon contractures and equinovarus feet deformity; he could not heel walk, had lower leg muscles wasting and, to a lesser extent, of the thenar and hypothenar eminence. His muscle power was within normal limits except for subgravity ankles plantar and dorsiflexion; deep tendon reflexes were preserved. The electrophysiology was suggestive of a motor neuronopathy. His younger sister presented in her teens with similar problems associated with mild hands weakness. Her electrophysiology was suggestive of a motor neuronopathy while the muscle MRI of the legs was suggestive of a distal myopathy. Their father presented in his forties with increased walking difficulties and frequent falls. The whole exome analysis in these affected individuals unrevealed two independent mutations: a heterozygous Myosin Heavy Chain 7 gene mutation (MYH7, g.23884965C > T,c.5030G > A, p.R1677H) and a heterozygous mutation in the Berardinelli-Seip Congenital Lypodystrophy type 2 gene (BSCL2, g.62469971T > G, p.N88S), present in each of the affected individuals. Our report highlights the power of whole exome sequencing in identifying the mutation load responsible for the phenotype in this family and suggests that “double trouble” of conditions with overlapping clinical features may be easily missed by more traditional diagnostic approaches.