title: SEPN1-related myopathies: clinical course in a large cohort of patients.
abstract: OBJECTIVE
  To assess the clinical course and genotype-phenotype correlations in patients with selenoprotein-related myopathy (SEPN1-RM) due to selenoprotein N1 gene (SEPN1) mutations for a retrospective cross-sectional study.
  
  
  METHODS
  Forty-one patients aged 1-60 years were included. Clinical data including scoliosis, respiratory function, and growth measurements were collected by case note review.
  
  
  RESULTS
  Mean age at onset was 2.7 years, ranging from birth to the second decade of life. All but 2 remained independently ambulant: one lost ambulation at age 5 years and another in his late 50s. The mean age of starting nocturnal noninvasive ventilation (NIV) was 13.9 years. One child required full-time NIV at the age of 1 year while in 2 cases NIV was started at 33 years. Two patients died from respiratory failure at the age of 10 and 22 years, respectively. The mean age at scoliosis onset was 10 years, in most cases preceded by rigidity of the spine. Fourteen patients had successful spinal surgery (mean age 13.9 years). Twenty-one were underweight; however, overt feeding difficulties were not a feature.
  
  
  CONCLUSIONS
  This study describes the largest population affected by SEPN1-RM reported so far. Our findings show that the spectrum of severity is wider than previously reported. Respiratory insufficiency generally develops by 14 years but may occur as early as in infancy or not until the fourth decade. Motor abilities remain essentially static over time even in patients with early presentation. Most adult patients remain ambulant and fully employed.
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, WC1N 1EH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Scoto
authors.forename: S
authors.initials: S
authors.lastname: Cirak
authors.forename: R
authors.initials: R
authors.lastname: Mein
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.forename: S
authors.initials: S
authors.lastname: Robb
authors.forename: A-M
authors.initials: AM
authors.lastname: Childs
authors.forename: R M
authors.initials: RM
authors.lastname: Quinlivan
authors.forename: H
authors.initials: H
authors.lastname: Roper
authors.forename: D H
authors.initials: DH
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Longman
authors.forename: G
authors.initials: G
authors.lastname: Chow
authors.forename: M
authors.initials: M
authors.lastname: Pane
authors.forename: M
authors.initials: M
authors.lastname: Main
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.forename: C
authors.initials: C
authors.lastname: Sewry
authors.forename: S
authors.initials: S
authors.lastname: Abbs
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation; D051140:Selenoproteins / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; C435489:SELENON protein, human; D051140:Selenoproteins