Congenital myopathies in adults: A diagnosis not to overlook

Autores da FMUP

• Joana Da Cruz Guimarães Ferreira De Almeida

  Autor

Participantes de fora da FMUP

• Pinto, M.
• Passos, BA
• Grangeia, A.
• Braz, L.

Unidades de investigação

• Neurociências Clínicas e Saúde Mental

Abstract

Background Congenital myopathies (CM) were traditionally classified according to the muscle histopathological features, but in recent years, molecular diagnosis has become increasingly important. CM may present a wide phenotype variability, and while adult-onset CM have been increasingly recognized, substantial diagnostic delays are still reported. Objectives To describe a cohort of adult CM patients, including clinical, genetic, and histopathological features, and further characterize the subgroup of adult-diagnosed patients. Materials and Methods We performed a retrospective observational cohort study to characterize the CM patients evaluated in our adult Neuromuscular outpatient clinic, including the subgroup of adult-diagnosed patients. Results We identified 19 CM patients with compatible molecular and/or histological diagnoses, of which 14 were diagnosed in adulthood. Eleven adult-diagnosed patients had symptoms since childhood and 9 had a family history of myopathy. The median age of symptoms onset was 4 years old and the median age at diagnosis was 37 years old. The most common causative gene was RYR1, followed by TTN and MYH7. Three patients had non-specific features on muscle biopsy, all diagnosed during adulthood. Conclusions In our cohort, the majority of CM were diagnosed in adulthood, despite most having pediatric-onset symptoms and positive family history. The diagnostic delay may be associated with mild presentation, slow course, atypical muscle histology, and lack of awareness of adult-onset CM. Studies with larger populations are needed.

Keywords

• congenital myopathy; histology; MYH7; RYR1; TTN