Oculo-dento-digital dysplasia: lack of genotype-phenotype correlation for GJA1 mutations and usefulness of neuro-imaging

Eur J Med Genet. 2010 Jan-Feb;53(1):19-22. doi: 10.1016/j.ejmg.2009.08.007. Epub 2009 Oct 4.

Abstract

Oculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder with complete penetrance and high intra- and interfamilial phenotypic variability. The key features in this syndrome are microphthalmia, enamel hypoplasia and syndactyly of the 4th-5th fingers. ODDD is caused by mutations in the connexin 43 gene (GJA1). We report here four patients from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patients had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leads us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Child, Preschool
  • Connexin 43 / genetics*
  • Dental Enamel Hypoplasia / genetics
  • Diagnostic Imaging*
  • Eye Abnormalities / genetics*
  • Female
  • Fingers / abnormalities
  • Genotype
  • Humans
  • Hypospadias / genetics
  • Intellectual Disability / genetics
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Sequence Analysis, DNA
  • Syndactyly / genetics*
  • Tooth Abnormalities / genetics*
  • Young Adult

Substances

  • Connexin 43
  • GJA1 protein, human