Two male sibs with severe micrognathia and a missense variant in MED12

Eur J Med Genet. 2016 Aug;59(8):367-72. doi: 10.1016/j.ejmg.2016.06.001. Epub 2016 Jun 7.

Abstract

Missense variants in MED12 cause three partially overlapping dysmorphic X-linked intellectual disability (XLID) syndromes: Lujan-Fryns syndrome (also known as Lujan syndrome), FG syndrome (also known as Opitz-Kaveggia syndrome) and X-linked Ohdo syndrome. We report a family with two severely micrognathic male sibs, a 10½ year old boy and a fetus, in which hemizygosity for a previously unreported missense variant in exon 13 of MED12 (NM_005120.2), c.1862G > A, p.(Arg621Gln) was detected by whole exome sequencing. The affected sibs shared no other rare variant with relevance to the phenotype. X-chromosome inactivation in blood was completely skewed (100:0) in the unaffected heterozygous mother, most likely as a result of preferential inactivation of the X-chromosome harbouring the missense variant in MED12. Neither the unaffected brother nor the unaffected maternal grandfather carried the missense variant in MED12. In the 10½ year old boy, upper airway obstruction secondary to Pierre Robin sequence necessitated a tracheostomy for the first 10 months of life. He has mild to moderate intellectual disability and some dysmorphic features seen in MED12-related syndromes. In addition, he has a horizontal gaze paresis, anomalies of the inner ear, and a cervical block vertebra. This report contributes to the expanding phenotypic range associated with MED12-mutations.

Keywords: Intellectual disability; MED12; Mental retardation; Micrognathia; X-linked.

Publication types

  • Case Reports

MeSH terms

  • Exons
  • Genes, X-Linked
  • Genetic Association Studies
  • Genotype
  • Humans
  • Infant
  • Male
  • Mediator Complex / genetics*
  • Micrognathism / diagnosis*
  • Micrognathism / genetics*
  • Mutation, Missense*
  • Pedigree
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Severity of Illness Index
  • Siblings*
  • Tomography, X-Ray Computed
  • X Chromosome Inactivation

Substances

  • MED12 protein, human
  • Mediator Complex