Congenital myopathies

Most affected individuals present at birth or in early infancy with generalised muscle weakness, hypotonia, hyporeflexia, poor muscle bulk, and, in some cases, dysmorphic features related to facial muscle weakness. Although onset is typically neonatal, milder phenotypes may not become apparent until later in childhood or adulthood. Subtypes are traditionally distinguished on muscle biopsy by the predominant structural change: rod-like inclusions (), central cores or multiple minicores (, including central core disease and multi-minicore disease), centrally placed myofibre nuclei (centronuclear and X-linked myotubular myopathy), and selective type-1 fibre hypotrophy (congenital fibre-type disproportion). Histopathologically oriented classification remains in widespread clinical use, although molecular diagnosis is increasingly central to nosology and case definition. A substantial proportion of cases show nonspecific histopathological changes that do not map to a single classical category, which complicates biopsy-based subtyping in routine practice.

The prevalence is estimated at approximately 1-5 per 100,000 live births, although reported estimates vary depending on the population studied. For example, a population-based study from Western Sweden reported an estimated prevalence of 3.9 per 100,000 inhabitants and a birth prevalence of approximately 14.9 per 100,000 live births. Among affected individuals, approximately 4 in 5 are reported to have an identifiable molecular genetic cause.

A large number of genes have been associated with congenital myopathies. The forms divide into nemaline, core, centronuclear, and other categories. The genetic spectrum varies across populations, with RYR1 being the most frequently identified gene in European cohorts. Other important genetic causes include NEB-associated nemaline myopathy and MTM1-associated X-linked myotubular myopathy.

The inheritance patterns associated with congenital myopathies include autosomal dominant, autosomal recessive, and X-linked inheritance.

• Where congenital myopathies are suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Michael E, Hedberg-Oldfors C, Tulinius M, Nordström S, Oldfors A, Darin N. Incidence and prevalence of congenital myopathies: a population-based study from Western Sweden. Ann Neurol. 2026;99(2):382-392. PMID: .
• de Feraudy Y, Vandroux M, Romero NB, Schneider R, Saker S, Boland A, et al. Exome sequencing in undiagnosed congenital myopathy reveals new genes and refines gene-phenotype correlations. Genome Med. 2024;16(1):87. PMID: .
• Huang K, Bi FF, Yang H. A systematic review and meta-analysis of the prevalence of congenital myopathy. Front Neurol. 2021;12:761636. PMID: .