EP.123Selenoprotein-related congenital myopathy in two siblings

Abstract

Selenoprotein-related myopathy (SEPN1-RM) is a rare disease with a variable clinical presentation. Typically, patients have early onset respiratory insufficiency and relatively preserved limb muscle strength. Although the precise function of SEPN1 protein is uncertain, recent studies suggest a role in cell protection against oxidative stress. Prominent involvement of diaphragm muscle and skeletal muscle which are more vulnerable to oxidative stress probably may cause early respiratory involvement. Here we report two siblings with presenting early respiratory failure unrelated to limb weakness. 13 years-old girl was referred to hospital for weakness, coliosis, respiratory failure and growth retardation since 5 years. She was borned with uncomplicated delivery from consanguineous parents. Early neurodevelopment was normal. At 5 years old, she had been treated with growth hormone therapy because of short stature. Also, she was operated for scoliosis before 1 year from admission and used nocturnal noninvasive ventilator since then. On examination, she had myopathic face, scapular winging, muscle wasting, scoliosis, spinal rigidity and positive Gower's sign. Deep tendon reflexes were absent. Muscle strength was 3/5 in upper and 4/5 in lower extremities. SEPN1-RM was suspected based on a positive Gowers' sign, calf amyotrophy, limb-girdle dystrophy, rigid cervical spine and prominent and early nocturnal respiratory failure. A homozygous, known c.817G>A (p.Gly273Arg) mutation in the SEPN1 gene was detected. Her 8 year old brother also examined because of frequent falls. He had mild axial hypotonia, generalised muscle atrophy, rigid cervical spine and facial weakness. He had also same mutation. Morning headaches, daytime fatigue and mild nighttime snoring raised suspicion of nocturnal hypercapnia. After initiation of non-invasive ventilation, sleep quality improved and the headaches disappeared. Early respiratory failure in contrast to preserved skeletal muscle strength is a striking clue for this type of myopathy. Respiratory functions, especially in nighttime, should systematically and frequently be screened in all patients with SEPN1-RM. Early diagnosis is life-saving for patients to provide nocturnal noninvasive respiratory support.