Characteristics of the rigid spine syndrome due to SEPN-1 myopathy. A long-term follow-up series of 21 patients

Abstract

SEPN-1 related myopathy is a recessive autosomal disorder caused by SEPN1 gene mutations. Patients present homogeneous clinical features, in particular a striking cervico-axial hypotonia and a weakness associated with poor head control. A progressive spinal stiffness and severe restrictive respiratory insufficiency with diaphragmatic failure is observed in the course of the first or second decade. They are described as a “rigid spine syndrome” (RSMD1). The aim of this study was to describe the course of the spinal deformity and the clinical and respiratory complications. We reviewed retrospectively the medical charts of 21 patients with mutations in the SEPN1 gene. Genetic, clinical, radiological (X-rays) and respiratory studies (spirometry) were reviewed and analyzed. Mean age at last follow-up was 23 years (4–55). All patients except one, showed poor weight and height for their age, with a mean body mass index of 13.3 kg/m 2 (8–25). Mechanical ventilation was required in 19 patients (age range 4–15), usually only nocturnally, but in three cases a tracheostomy was performed. Four patients lost walking at a mean age of 28 (12–44). Clinical and radiological examinations were available for 15. Cervical spine stiffness was present in 65% of patients (mean chin–sternum distance in maximal cervical flexion of 7 cm). Scoliosis was observed in 12 (7 spinal translation; 6 pelvic obliquity). Clinically, a thoracic lordosis was observed in 87% of patients, and X-ray showed a flat thoracic spine. Management of the spinal deformity was focused mainly in axial stretching and antilordotic bracing. Two cases developed a severe progressive scoliosis before puberty. Spinal surgery was performed in 15 patients. SEPN1-related myopathy should be suspected in children developing a characteristic stiff and lordotic thoracic spinal deformity associated with a cervical rigidity. Due to constant respiratory complications, these patients require specialized multidisciplinary management.