Large phenotypic variability with severe respiratory involvement in MEGF10-related myopathies: Description of three...

MEGF10 biallelic variants cause early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD), congenital myopathies with cores, and later-onset myopathies with respiratory failure. As MEGF10 plays a key role in satellite cells proliferation and differentiation, these disorders are considered primary Satellite Cell-opathies. We present clinical, genetic, and laboratory findings from three patients with MEGF10-related myopathy from two families: a 6-year-old boy with EMARDD, and two siblings with a milder myopathy with respiratory involvement. Patient 1, male, showed decreased fetal movements and profound neonatal hypotonia with respiratory failure, requiring tracheostomy soon after birth. At 6 years, he had lack of head and trunk control, scoliosis, and upper limbs antigravity movements. Muscle MRI revealed mild-to-moderate, symmetrical fibro-fatty replacement affecting scapular, paravertebral, gluteal and adductor muscles, with bilateral absence of the semimembranosus. Muscle biopsy revealed a reduction of Pax7-positive satellite cells. Genetic studies disclosed the novel homozygous MEGF10 c.337T>C, p.(Cys113Arg) variant. Patient 2 is a 24-year-old woman with myopathic facies, progressive axial and generalized weakness, and thoracolumbar scoliosis at 11 years, leading to progressive respiratory involvement necessitating tracheostomy at 14 years. Her 17-year-old brother, patient 3, experienced a threatened abortion and perinatal complications consisting of neonatal hypoxia, right arm monoplegia, and clavicle fracture, followed by motor delay, scoliosis and progressive respiratory dysfunction, requiring non-invasive ventilation at 16 years. P2 and P3 harbour the novel homozygous c.917G>C, p. (Arg306Pro) MEGF10 pathogenic variant. We describe three new patients with MEGF10-related myopathy, showing severe but variable clinical expression, associated with two novel variants.