Concurrent occurrence of an inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving MAP2K2 in a patient with developmental delay, distinctive facial features, and lambdoid synostosis

Eur J Med Genet. 2016 Nov;59(11):559-563. doi: 10.1016/j.ejmg.2016.10.006. Epub 2016 Oct 14.

Abstract

A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2), in which mutations cause the cardio-facio-cutaneous (CFC) syndrome. Reports of patients with overlapping 19p13.3 microdeletions of this region describe similar clinical manifestations including distinctive facial features: prominent forehead, horizontal/down-slanting palpebral fissures, long midface, pointed chin/angular jaw, sparse eyebrows, and underdeveloped cheekbones. Some of these findings overlapped to that of the patients with 16p13.11 microduplications and CFC syndrome. Although craniosynostosis was occasionally observed in patients with dominant-negative mutations in RAS/MAP kinase signaling genes (RASopathies) related to CFC syndrome, it was also reported in two patients with 16p13.11 microduplications. Genetic contributions of both chromosomal aberrations were discussed.

Keywords: 16p13.11 microduplication; 19p13.3 microdeletion; Lambdoid synostosis; MAP2K2.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics
  • Chromosome Duplication / genetics
  • Chromosomes, Human, Pair 16 / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • Craniosynostoses / genetics*
  • Craniosynostoses / physiopathology
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • Ectodermal Dysplasia / genetics*
  • Facies
  • Failure to Thrive / genetics*
  • Female
  • Heart Defects, Congenital / genetics*
  • Humans
  • Infant
  • Karyotype
  • MAP Kinase Kinase 2 / genetics*
  • Mutation
  • Phenotype

Substances

  • MAP2K2 protein, human
  • MAP Kinase Kinase 2

Supplementary concepts

  • Cardiofaciocutaneous syndrome