Characterization of a Norwegian cherubism cohort; molecular genetic findings, oral manifestations and quality of life

Eur J Med Genet. 2013 Mar;56(3):131-7. doi: 10.1016/j.ejmg.2012.12.008. Epub 2013 Jan 5.

Abstract

Bilateral multilocular radiolucencies of the mandible are the main feature of cherubism (OMIM #118400), a rare autosomal dominant disorder primarily affecting the jaw. Typically, symmetrical swelling of the lower face is evident from around three years of age and increases until puberty. The underlying radiolucent lesions consist of vascular fibrotic stroma with scattered multinuclear giant cells. By age 30 years the facial contours are often unremarkable. Missing and displaced teeth as well as premature tooth loss are characteristic. Diagnosis rests upon a combination of clinical, radiographic, histological and molecular findings. SH3BP2 is currently the only gene known to be associated with cherubism. This cross-sectional study describes oral manifestations, quality of life and results of mutation analysis of SH3BP2 in 11 females and 13 males ages five to 84 years with cherubism. One individual with molecularly confirmed Noonan syndrome was excluded from the cohort. Standard statistical tools were used to analyze quality of life data. Mutation analysis was positive in all 22 familial and negative in both sporadic cases. Disease manifestations in mutation carriers varied from none to severe. Although intra-familial variability was marked, we found no evidence of non-penetrance, and females were on average more severely affected than males. Dental sequelae were pronounced; adults lacked a mean of 13 teeth (range 2-28), 13 of 17 individuals aged 16 years and older had removable or fixed dentures and five had dental implants; implant survival rate was 79%. In spite of pronounced disease manifestations and dental sequelae, adult quality of life was good.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cherubism / diagnosis*
  • Cherubism / genetics*
  • Cherubism / pathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Jaw / pathology
  • Male
  • Middle Aged
  • Mutation, Missense
  • Norway / epidemiology
  • Pedigree
  • Penetrance
  • Quality of Life*
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • SH3BP2 protein, human