SEPN1 Related Myopathy Presenting as Chronic Respiratory Insufficiency

To the Editor: A 6-y-old girl presented with features of respiratory distress and there was a history of hospitalization; first in the neonatal period for respiratory distress, at 2.5 and 4 y for pneumonia requiring continuous positive airway pressure (CPAP). The clinical pointers which suggested underlying neuromuscular disease were, delayed motor milestones, proximal myopathy, waddling gait with scoliosis, lumbar lordosis and limited spine flexion, digital clubbing, diminished tendon reflex and chronic respiratory acidosis. Creatine phosphokinase (CPK), homocysteine, T3, T4, thyroid stimulating hormone (TSH), tandem mass spectroscopy (TMS), gas chromatography mass spectrometry (GCMS), angiotensin-converting enzyme (ACE), antinuclear antibody (ANA), rheumatoid factor, C3, C4, Anti-dsDNA, cytoplasmic anti-neutrophil cytoplasmic autoantibody (c-ANCA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), Gene expert, electromyography (EMG), nerve conduction velocity (NCV) and clinical exome were normal. Computed tomography (CT) thorax revealed bilateral multifocal patchy areas of mixed GGO and multiple focal asymmetrical areas of perihilar and peri-bronchovascular collapse consolidation reaching up to periphery. Echocardiography and CT thorax angiography confirmed dilatation of pulmonary trunk and pulmonary hypertension. Whole exome sequencing revealed a heterozygous missense variation in exon 11 of the Selenoprotein N1 (SEPN1) gene (chr1:g.25813890G>A; depth:99x) that results in the amino acid substitution of Glutamine for Arginine at codon 466 (p.Arg466Gin). Polysomnography showed nocturnal hypoventilation. Child was discharge on Bi-level-positive airway pressure (BiPAP) and nocturnal oxygen saturation monitoring. …