Muenke syndrome with pigmentary disorder and probable hemimegalencephaly: An expansion of the phenotype

Am J Med Genet A. 2011 Jan;155A(1):207-14. doi: 10.1002/ajmg.a.33777.

Abstract

We describe a 2-year-old boy born to healthy, consanguineous parents. He had craniofacial asymmetry with left frontal bossing, midface hypoplasia, proptosis, and low-set ears. In addition, he had curly, light hair, and oval hypomelanotic patches in the abdomen, lower limbs and back and one hyperpigmented patch in the groin without acanthosis nigricans. Cranial three-dimensional CT scan showed right-coronal, sagittal, and lambdoid suture synostoses. His cranial MRI at 2-months of age showed left hemimegalencephaly, hypoplasia of corpus callosum, and an abnormal configuration of hippocampus. In spite of these cranial findings, he had mild developmental delay and his neurological examination showed symmetric strength, tone and reflexes. Apart from febrile seizures, there was no history of epilepsy. The proband developed asymmetric hydrocephalus at the age of 18 months that required third ventriculostomy. Post-operative cranial MRI showed Chiari I- like malformation and asymmetry of cerebral hemispheres but less dysplastic cerebral cortex. Mutation analysis of FGFR3 showed a c.749C > G, p.Pro250Arg substitution. To the best of our knowledge, these manifestations have not been reported in patients with Muenke syndrome.

Publication types

  • Case Reports

MeSH terms

  • Brain / pathology*
  • Child, Preschool
  • Craniosynostoses / genetics
  • Craniosynostoses / pathology
  • DNA Mutational Analysis
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Malformations of Cortical Development / genetics
  • Malformations of Cortical Development / pathology*
  • Mutation, Missense / genetics
  • Pigmentation Disorders / genetics
  • Pigmentation Disorders / pathology*
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*

Substances

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

Supplementary concepts

  • Muenke Syndrome