The FHL1 myopathy spectrum revisited: a literature review and report of two new patients.

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