Phenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark.

OBJECTIVE

Congenital myopathy as a nosologic entity has long been recognized, but knowledge of overall and subtype prevalence and phenotype-genotype relationship is scarce, especially in the adult population.

METHODS

A national cohort of 107 patients ≥5 years diagnosed with congenital myopathy were prospectively assessed clinically, histologically, and genetically.

RESULTS

Twenty-five patients were excluded because of atypical features or alternative etiologies. The remaining 82 were on average 28 years old. Histologic examination revealed 14 (17%) with core disease, 15 (18%) centronuclear myopathy, 12 (15%) nemaline rods, 27 (33%) congenital fiber-type disproportion or type I predominance, and 14 (17%) nonspecific myopathic changes. Genetic etiology was identified in 46 patients (56.1%); 22.0% were heterozygous or compound heterozygous for mutations in , 7.3% had mutations, and 7.3% mutations. Less than 5% had mutations in , , , , , or . A genetic cause was established in 83% with specific histology (cores/rods/centronuclear myopathy) vs 29% with unspecific histology. The detailed clinical examination found gene-dependent discrepancies in the pattern of muscle affection and walking ability. Although walking ability was delayed in patients with , , and mutations, it was within normal limits in patients with and mutations.

CONCLUSIONS

We found that overall, genetic and histologic prevalence of congenital myopathy in Denmark differs from previous retrospective reports. Less and more and mutations and less core histology were present in our cohort. These differences may be explained by our prospective design, the older cohort of patients, and by differences in genetic background.