Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus

In 1995 Laing et al. (Am J Hum Genet 56(1995)422) described a single family with nine members affected by an autosomal dominant infantile onset distal myopathy. This family generated a LOD score of 2.6 for a locus on chromoso me 14. We describe two families with an infantile onset distal myopathy: a new family with four affected members and the family previously described b y Scoppetta et al. (Acta Neurol Scand 92(1955)122) in both of which haploty pe segregation was compatible with linkage to the same chromosome 14 locus, generating LOD scores of 0.9 at a penetrance of 100% for the markers D14S2 83 and D14S64 (theta = 0) in both families. The loci for autosomal recessiv e hereditary inclusion body myopathy and Nonaka myopathy on chromosome 9 an d for autosomal dominant distal myopathy of Markesberry-Griggs and Udd on c hromosome 2q31-33 were excluded by linkage analysis. The disease followed a uniform course with selective wasting of the anterior tibial muscles, star ting in infancy and recognizable by a characteristic clinical sign of the ' hanging big toe'. This was followed by slow progression, with involvement o f the finger and wrist extensor muscles in the third decade and proximal li mb muscles in the fourth decade. Interestingly, we also found evidence of a n accompanying mild peripheral neuropathy in the oldest individual with hyp omyelination of numerous large myelinated fibres. In addition, this patient 's muscle biopsy also showed autophagic vacuoles and numerous intranuclear tubulo-filamentous inclusions of 15-20 nm diameter. Given that all three fa milies with infantile onset distal myopathy are compatible with linkage to the same locus on chromosome 14, this study supports evidence for, and enla rges the clinical and neuropathological spectrum of the distal myopathy on chromosome 14. (C) 2001 Elsevier Science B.V. All rights reserved.