Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease

Eur J Hum Genet. 2016 Aug;24(8):1216-9. doi: 10.1038/ejhg.2015.276. Epub 2016 Jan 27.

Abstract

CHD7 variants are a well-established cause of CHARGE syndrome, a disabling multi-system malformation disorder that is often associated with deafness, visual impairment and intellectual disability. Less severe forms of CHD7-related disease are known to exist, but the full spectrum of phenotypes remains uncertain. We identified a de novo missense variant in CHD7 in a family presenting with musculoskeletal abnormalities as the main manifestation of CHD7-related disease, representing a new phenotype. The proband presented with prominent scapulae, mild shoulder girdle weakness and only subtle dysmorphic features. Investigation revealed hypoplasia of the trapezius and sternocleidomastoid muscles and semicircular canal defects, but he did not fulfill diagnostic criteria for CHARGE syndrome. Although the shoulders are often sloping and anteverted in CHARGE syndrome, the underlying neuromuscular cause has never been investigated. This report expands the phenotypes associated with CHD7 mutations to include a musculoskeletal presentation, with hypoplasia of the shoulder and neck muscles. CHD7 should be considered in patients presenting in childhood with stable scapular winging, particularly if accompanied by dysmorphic features and balance difficulties.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CHARGE Syndrome / diagnosis
  • CHARGE Syndrome / genetics*
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • Diagnosis, Differential
  • Female
  • Humans
  • Infant
  • Male
  • Musculoskeletal Abnormalities / diagnosis
  • Musculoskeletal Abnormalities / genetics*
  • Mutation, Missense
  • Neck Muscles / pathology
  • Pedigree
  • Phenotype*
  • Scapula / abnormalities*

Substances

  • DNA-Binding Proteins
  • DNA Helicases
  • CHD7 protein, human