FHL1‐mutated reducing body myopathy

Abstract

Here, we report about reducing body myopathy, associated with a mutation in the four and a half LIM domain 1 gene (FHL1), identified in a 40‐year‐old woman who was suffering from subtle muscle weakness since the age of six and a limping gait since the age of 22 years. In addition to her elevated muscle enzyme level and magnetic resonance imaging, myopathy was highly suspected considering progression of symptoms. Nerve conduction studies and electromyogram suggested myopathy. The muscle biopsy revealed severe dystrophic features with many reducing bodies on hematoxylin and eosin, nicotinomide adenine dinucleotide dehydrogenase‐tetrazolium reductase (NADH‐TR), and modified Gomori stains and ubiquitin immunohistochemistry. Whole‐exome sequencing revealed Xq26.3 encoding FHL1 missense mutations (NM_001159704) in exon 4: p.C150R, c.T448C. FHL1‐mutated “reducing body myopathy” is worth reporting based on its rarity and unique clinicopathologic features including ultrastructure. The confirmative diagnosis is still very difficult before gene analysis because clinical and pathological features of this disease overlap with other myofibrillar myopathies. We stress the importance of genotype‐phenotype correlation to obtain a precise diagnosis.

A comprehensive study of skeletal muscle imaging in FHL1‐related reducing body myopathy

“…In rare myopathies like FHL1 ‐related RBM, muscle imaging modalities hold promise as disease biomarkers to facilitate diagnosis and to help monitor disease progression and empower interventional clinical trials 10–12 . In a few case studies of FHL1 ‐related RBM patients, muscle MRI studies have suggested a distinct pattern of muscle involvement in the lower extremities: sparing of gluteus maximus muscle, and selective involvement of posteromedial thigh muscles, medial gastrocnemius, and soleus muscles 13–16 . Muscle ultrasound and cardiac MRI studies are not extensively reported in the literature in patients with FHL1 ‐related RBM.…”

“… 10 , 11 , 12 In a few case studies of FHL1 ‐related RBM patients, muscle MRI studies have suggested a distinct pattern of muscle involvement in the lower extremities: sparing of gluteus maximus muscle, and selective involvement of posteromedial thigh muscles, medial gastrocnemius, and soleus muscles. 13 , 14 , 15 , 16 Muscle ultrasound and cardiac MRI studies are not extensively reported in the literature in patients with FHL1 ‐related RBM.…”