SelenoproteinN1-related myopathy: From clinical signs to diagnosis

Introduction: Selenoprotein N1 (SEPN1)-related myopathies are caused by mutations in the SEPN1 gene and form a group of rare disorders, whose incidence and prevalence is unknown so far. The inheritance is autosomal recessive. The phenotype could be characterised by early muscular hypotonia, poor head control, axial muscle weakness, spinal rigidity with early scoliosis and respiratory distress with nocturnal hypoventilation. Most of the patients show dystrophy with body mass index (BMI) below the 3.rd percentile. Intelligence is mostly normal and weakness is often static or slowly progressive.

Case report: We report on a 2,7 year old boy, whose first presentation has been arranged due to weakness and dystrophy (BMI: 12,7kg/m²;<1. P. -3,06 SDS). Furthermore there could be found funnel chest, flat valgus feed, large ears, axial and proximal muscle weakness including lag of head control and positive Gowers sign and symptoms of respiratory hypoventilation during sleep. Pregnancy was uncomplicated, birth weight was normal, no feeding problems in the first months. Further motor development in the first year was normal (walking at 14 months). Speech development was in upper range, serum creatine kinase (CK) level and neurophysiologic investigations were normal. Because of the typical clinical appearance a genetic analysis in the SEPN1 gene was performed without a muscle biopsy before, which disclosed two missence mutations in the SEPN1 gene (c. 1 A>G or p. Met1Val in exon 1 and c. 973 G>A or p. Gly315 Ser in exon 7).

Conclusion: SEPN1 related myopathies are rare disorders and muscle biopsy may show non-specific changes. In our case the combination of history and typical clinical symptoms prompted to a direct genetic analysis in the SEPN1 gene. In those cases muscle biopsy can be omitted.