Choi et al. (2011) reported a large 5-generation Korean family with a complex phenotype of progressive peripheral neuropathy and distal myopathy, with later onset of hoarseness and hearing loss. Affected individuals developed distal muscle weakness at a mean ... Choi et al. (2011) reported a large 5-generation Korean family with a complex phenotype of progressive peripheral neuropathy and distal myopathy, with later onset of hoarseness and hearing loss. Affected individuals developed distal muscle weakness at a mean age of 10.6 years, followed by progressive atrophy of these muscles. The lower limbs were more severely affected than the upper limbs, and the muscle weakness first affected anterior leg muscles and later posterior leg muscles. Three older patients, around age 40 years, reported proximal weakness of the thigh muscles. Most patients had foot deformities and a- or hyporeflexia, although none had sensory loss. Eight (53%) of 15 patients had hoarse voice, but none had dysphagia or vocal cord paresis. Audiologic studies showed late-onset sensorineural hearing loss in 5 (45%), all of whom were older than 28 years. Serum creatine kinase was mildly increased only in a few patients. Nerve conduction studies showed mildly reduced or normal sensory values, but peroneal nerves showed severely reduced compound motor action potentials (CMAPs). MRI showed fatty replacement in affected muscles, and muscle biopsies of 2 patients showed variation of fiber size and shape and subsarcolemmal accumulation of enlarged mitochondria with variably sized rectangular or elongated rhomboidal paracrystalline inclusions. The findings were consistent with both a myopathic and a neuropathic process.
By candidate gene sequencing in the 19q13.3 linkage region for the phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss, Choi et al. (2011) identified a heterozygous mutation in the MYH14 gene (608568.0006).