Molecular and Clinical Characteristics of a National Cohort of Paediatric Duchenne Muscular Dystrophy Patients in Norway

J Neuromuscul Dis. 2019;6(3):349-359. doi: 10.3233/JND-190402.

Abstract

Background: As new gene-related treatment options for Duchenne muscular dystrophy (DMD) are being developed, precise information about the patients' genetic diagnosis and knowledge about the diversities of natural history in DMD is vital.

Objective: To obtain detailed insight into the genetic and clinical characteristics of paediatric DMD in Norway.

Methods: 94 boys with DMD, aged 0-18 years, were identified over a period of 3.5 years, yielding a national prevalence of 13.5×10-5 boys. 73 boys (78%) were recruited to full genetic and clinical or limited (genetic only) evaluation.

Results: Molecular analysis disclosed 64% deletions, 18% duplications and 18% point mutations. The mean age of diagnosis was 3.9±2.0 years. 78% were treated with glucocorticoids from age 5.8±1.5 years. 23 boys (35%) had lost ambulation at an age of 10.7±2.0 years. 17% were treated for left ventricular dysfunction from age 12.1±3.0 years and 12% had received night-time non-invasive positive pressure ventilation from age 13.0±2.5 years.

Conclusions: The distribution of mutation types and sites was similar to previous studies but with more duplications and fewer point mutations. Any genotype-phenotype correlations were not uncovered. The boys were diagnosed early but there is still diagnostic delay among boys presenting with late motor development. Glucocorticoid treatment was widespread, especially among the younger boys. The clinical results of this comprehensive nationwide study highlight the large variability of disease progression in DMD.

Keywords: Duchenne muscular dystrophy; ambulation; cardiopulmonary; disease progression; genotype-phenotype correlation; glucocorticoid.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease Progression
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Muscular Dystrophy, Duchenne / diagnosis*
  • Muscular Dystrophy, Duchenne / epidemiology
  • Muscular Dystrophy, Duchenne / genetics*
  • Mutation
  • Norway / epidemiology