Reducing Body Myopathy in Female Patients With FHL1 Variants Showing Rapid and Severe Evolution Mimicking...

Reducing body myopathy (RBM) is a rare inherited disorder, due to pathogenic variant in the FHL1 gene. The disease is characterized by protein aggregates in myocytes strongly stained with menadione-nitro blue tetrazolium with α-glycerophosphate and immunoreactive for FHL1 as myopathologic hallmarks. RBM is an X-linked dominant disorder, with the most severe cases occurring in hemizygous sporadic male patients, who usually present with early onset and rapid progression. This study aimed to comprehensively analyse a cohort of FHL1 female patients presenting with a severe and rapidly progressive phenotype clinically mimicking an inflammatory idiopathic myopathy.

This is retrospective study of a cohort of female patients with RBM harboring pathogenic variants in FHL1 gene from France and Italy. Data regarding clinical onset and progression, myopathologic features, muscle imaging, and genetic testing have been collected retrospectively and analyzed from medical records.

We present 5 young girls and women with FHL1 pathogenic variants presenting a mean age at onset of 13 years. All patients showed an asymmetric pattern of muscle weakness evolving in bilateral proximo-distal involvement and restrictive respiratory syndrome, rapidly leading to severe tetraparesis and loss of ambulation after a mean period of 6.2 years in 4 of them. Serum CK level at onset was slightly elevated with a mean value of 539 UI/L. Muscle MRI revealed severe asymmetric proximo-distal involvement with STIR positive sequences. Muscle biopsies showed reducing bodies and prominent autophagic material accumulation.

FHL1-related reducing body myopathy can present with a rapidly progressive muscle weakness mimicking an inflammatory myopathy also in female patient. Muscle biopsy is an useful tool in the contest of rapidly progressive myopathy to distinguish between genetic myopathies and treatable inflammatory myopathy.