Neuroimaging and neurological findings in patients with hypochondroplasia and FGFR3 N540K mutation

Am J Med Genet A. 2012 Dec;158A(12):3119-25. doi: 10.1002/ajmg.a.35642. Epub 2012 Nov 19.

Abstract

Hypochondroplasia (HCH), an autosomal dominant skeletal dysplasia caused by mutations in the FGFR3 gene, has not been commonly associated with neurological problems. Temporal lobe dysgenesis associated with epilepsy was recently described in single patients. In this retrospective study, we assessed neurological and neuroimaging aspects of 13 FGFR3 (N540K) mutation verified HCH patients in Finland. Eight patients had neurocognitive difficulties, ranging from specific learning disorder (2/13) to mild intellectual disability (5/13) or global developmental delay (1/13). Six of 13 patients had a history of seizures or epilepsy. Eight patients had undergone MRI. They all had structural abnormalities consistent with temporal lobe dysgenesis. Six patients had peritrigonal white matter reduction, and 4 had abnormally shaped lateral ventricles. We recommend a close follow-up of development in patients with HCH and a low threshold for neuroimaging.

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Bone and Bones / abnormalities
  • Bone and Bones / pathology
  • Child
  • Child, Preschool
  • Dwarfism / diagnosis
  • Dwarfism / genetics*
  • Dwarfism / pathology*
  • Female
  • Finland
  • Humans
  • Infant
  • Limb Deformities, Congenital / diagnosis
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / pathology*
  • Lordosis / diagnosis
  • Lordosis / genetics*
  • Lordosis / pathology*
  • Male
  • Mutation*
  • Neuroimaging / methods
  • Psychomotor Disorders / diagnosis
  • Psychomotor Disorders / genetics
  • Psychomotor Disorders / pathology
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Retrospective Studies
  • Temporal Lobe / pathology

Substances

  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3

Supplementary concepts

  • Hypochondroplasia