MEGF10 gene mutations causing a recessive congenital multiminicore myopathy (P9-9.010)

Abstract

<h3>Objective:</h3> Congenital myopathies are classified into five main types: core myopathies, nemaline myopathies, centronuclear myopathies, congenital fiber-type disproportion, and myosin storage myopathies. The most common forms are core myopathies. Despite their phenotypic diversity, patients demonstrate common symptoms including hypotonia, muscle weakness, dysmorphic features, and respiratory problems. There are several mutations in <i>MEGF10</i> that have been reported to cause autosomal recessive congenital myopathy, areflexia, respiratory distress, muscle weakness, dysphagia with early or late-onset syndrome, minicore myopathy and limb girdle muscular dystrophy. Affected individuals frequently become ventilator dependent or die secondary to respiratory failure. <h3>Background:</h3> A 5-year-old girl from a consanguineous couple was referred to our service due to weakness and hypotonia. After birth, she developed respiratory failure. Severe motor delay was already evident in the first months of life: at 6 months she had no cervical control and at 12 months she could not sit without support. At age 3 she developed respiratory problems with apnea and hypercapnia, requiring ventilation with two levels of positive airway pressure. She was indicated for gastrostomy at age 4 after aspiration pneumonia. On her evaluation, she had axial and proximal muscle weakness, facial weakness, scoliosis, and nasal speech. Despite presenting hypotonia and gait difficulties, she was able to walk independently and had no cognitive changes. A muscle biopsy was performed which suggested multiminicore myopathy. Genetic investigation resulted in a homozygous mutation of the <i>MEGF10</i> gene. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> <i>MEGF10</i> mutations should be considered in the differential diagnosis of individuals with respiratory insufficiency and myopathy, particularly when accompanied by facial weakness, scoliosis or dysphagia. The phenotypic similarities with other congenital neuromuscular disorders may cause difficulties in reaching a definite diagnosis. Treatment with a multidisciplinary team is important and family counseling is essential since consanguineous unions play a role in recessive genetic mutations manifestations. <b>Disclosure:</b> Miss Faria has nothing to disclose. Dr. Barbosa has nothing to disclose. Mrs. Ribeiro Torres has nothing to disclose. Mr. E Souza Filho has received research support from Universidade Federal de Minas Gerais. Mrs. Thiersch has nothing to disclose. Mrs. Oliveira has nothing to disclose.