The FHL1 myopathy spectrum revisited: a Literature Review and report of two new patients

Objectives. Mutations in the FHL1 gene have been associated with a diverse spectrum of X-linked diseases affecting skeletal and cardiac muscle. Six clinically distinct human myopathies can be recognized, including reducing body myopathy (RBM), X-linked dominant scapuloperoneal myopathy (SPM), X-linked myopathy with postural muscle atrophy (XMPMA), rigid spine syndrome (RSS), hypertrophic cardiomyopathy (HCM) and type 6 Emery- Dreifuss muscular dystrophy (EDMD). The core features of all described FHL1opathies are mostly scapuloperoneal muscle weakness, rigid spine, cardiac involvement, and cytoplasmic bodies in the muscle biopsy.

Methods: We systematically reviewed the medical literature between the years 2000 and 2024 regarding the phenotype and genotype description of FHL1-associated myopathies

Results. Here, we report two novel patients presenting with an X-linked myopathy with postural muscle atrophy (XMPMA) caused by the c.672 C>G FHL1 gene mutation.

Conclusion. When encountering these features in a patient, one may consider screening for an FHL1 mutation. The course ranges from a severe fatal course with early onset to very mild features with late onset. Once a dystrophinopathy has been excluded, increased CK values in male subjects with possible X-linked inheritance should always trigger FHL1 gene screening.