The phenotype and genotype of congenital myopathies based on a large
We report the clinical, histopathological and molecular characterization
of 104 patients with congenital myopathy (CM) managed at a single
center. The most common histopathological subtype was core myopathy
(42%). Patients with severe endomysial fibrosis were more commonly
unable to walk than patients with only a mild grade (56% vs 16%).
Inability to walk was also more prevalent in patients with severe fatty
replacement (44% vs 19%). The genetic etiology was more frequently
identified among those patients with “specific” histologic findings
(74% vs 62%). A definite molecular diagnosis was reached in 65/104
patients (62%), with RYR1 (24/104) and TTN (8/104) as the most frequent
causative genes. Neonatal onset occurred in 56%. Independent ambulation
was achieved by 74%. Patients who walked late were more likely to
become wheelchair-dependent. Respiratory support was needed in 1/3
patients. Gastrostomy placement was required in 15%. Cardiac
involvement was observed in 3%, scoliosis in 43%, and intellectual
disability in 6%. This study provides an updated picture of the
clinical, histopathological and molecular landscape of CMs.
Independently of the causative gene, fibrosis and fatty replacement in
muscle biopsy is significantly associated with clinical severity.
Mutations in TTN are responsible for a higher proportion of cases than