Neuropediatrics 2010; 41 - V1262
DOI: 10.1055/s-0030-1265524

Phenotype and long-term follow-up of juvenile Selenoprotein N1-related myopathy (SEPN1-RM)

M von der Hagen 1, W Kress 2, A Ferreiro 3, CG Bönnemann 4, U Grieben 5, CG Korenke 6, U Reuner 7, G Schreiber 8, M Stoetter 9, P Richard 10, E Willichowski 11, J Lütschg 12, U Schara 13
  • 1Dept. of Pediatric Neurology, Technical University Dresden, Germany
  • 2Institute of Human Genetics, Julius-Maximilians University Würzburg, Germany
  • 3U787 Groupe Myologie, INSERM/UPMC, Groupe Hospitalier Pitié-Salpêtriére, Paris, France
  • 4Division of Neurology and Neuromuscular Program, Children's Hospital of Philadelphia, USA
  • 5SPZ, Dept. of Pediatric Neurology, Charité, Berlin, Germany
  • 6Dept. of Pediatric Neurology, Klinikum Oldenburg, Germany
  • 7Dept. of Neurology, Technical University Dresden, Germany
  • 8Dept. of Pediatric Neurology, Klinikum Kassel, Germany
  • 9Dept. of Pediatric Neurology, University of Tübingen, Germany
  • 10UF de Cardiogénétique et Myogénétique, Groupe Hospitalier Pitié-Salpêtriére, Paris, France
  • 11Dept of Pediatric Neurology, Georg-August University Goettingen, Germany
  • 12Dept. of Pediatric Neurology, Children's Hospital, University beider Basel, Basel, Switzerland
  • 13Dept. of Pediatric Neurology, University of Essen, Germany

Introduction: The SEPN1-related myopathy (SEPN1-RM) is an autosomal-recessive early onset muscle disorder characterised by distinct myomorphologies.

Objective: To characterise the phenotype in juvenile SEPN1-RM.

Methods: Retrospective multicentre study of the clinical findings, histomorphological studies and genetic data of 26 juvenile patients (8 male, 18 female) with SEPN1-RM.

Results: Muscle biopsies of 22 individuals revealed multiminicores (n=7), congenital fiber-type disproportion (n=2), myopathic changes with single cores (n=3) and unspecific myopathic features (n=10). Genetic analyses showed a variable distribution of mutations in the SEPN1 gene. Age of manifestation varied within the first two years of life with muscle hypotonia, head lag and delayed motor development. 24/26 patients were ambulant for at least 500 metres at a mean age of 14.5 years. 22 patients exhibited a rigid spine (mean age: 11.8 years) and 22 individuals had a scoliosis (mean age: 9.2 years). 11/22 patients had a scoliosis operation (mean age: 12.6 years). Spirometry was available in 19 individuals and all revealed moderate to severe respiratory impairment with a vital capacity ranging from 24–65%. 15/26 patients were intermittently nocturnally ventilated (mean age: 11.2 years). Two children had a tracheotomy, one child died at the age of three years following acute respiratory failure. Cardiac investigations were performed in 21/26 patients and revealed a mitralvalve prolapse in one and sinustachycardia prior to non-invasive ventilation in two patients. Body mass index was below 20 (kg/m2) in 20/22 patients, mean BMI 14.2 (min. 11.1, max 22.1) at a mean age of 11.7 years. 16/20 children had a birth weight >3000 gram, 4/20 children weighed between 2000–3000 gram (all patients were delivered >36. week of gestation).

Conclusion: Respiratory impairment, deformity of the spine and low body mass index are major features in juvenile SEPN1-RM. Selective symptomatic treatment is important for these patients.