Distal myopathies represent a rare group of myopathies. A vast retrospective study, the largest on the subject, describes the characteristics of 219 patients followed in an expert center located in the Valence region of Spain.
Overall, symptoms start in adulthood with walking difficulties. Motor involvement is not always purely distal but also sometimes proximo-district. It can be associated with an involvement of the heart, diaphragm or peripheral nerves.
Sporadic cases more difficult to diagnose
The authors were able to establish with certainty the genetic diagnosis in 68% of cases. Most of them, anomalies were located in genes already identified in distal myopathies: Myh7 (laing myopathy), Ano5(anoctaminopathie), DYS (myopathie de Miyoshi), TTN (UDD type myopathy), Myot (myopathy myofibrillar), OF THE (myopathy myofibrillar), Gne (Nonaka myopathy), VCP (Myopatia with hereditary inclusions with Paget and Frontotemporal Dementia), DNM2 (Dynamine 2)… genes involved in other forms of myopathies have also been found.
The diagnosis was more difficult, especially for late forms, starting after 60 years and in the absence of a family history. In these people, the involvement was more often atypical, touching the proximal and distal muscles, but also the respiratory muscles and even the peripheral nerves.
Towards a broader detection of genetic anomalies thanks to new tools
A French study, supported by the AFM-Téléthon describes the diagnosis of a family with proximo-district myopathy with late start due to a duplication of the Myot gene, thanks to long-reading sequencing. This technique, used for only a few years, allows you to read long DNA sequences at one time and thus find genetic anomalies previously not detected by conventional technologies such as duplications, repetition expansion, inversions or deletions.
Source
Clinical features, mutation spectrum and factors related to reaching molecular diagnosis in a cohort of patients with distal myopathies
N, Road-Vilarrog L., Martin P. and to the. J Neurol 2025 Jan
Myotilin gene duplication causing late-onset myotilinopathy
Spinazzi M, Savase M, Letourne F et al. 9 Eur J Neurol . 2025 Jann
