Phenotype expansion and development in Kosaki overgrowth syndrome

Clin Genet. 2018 Apr;93(4):919-924. doi: 10.1111/cge.13192.


We expand the Kosaki overgrowth syndrome (KOGS) phenotype by over 70% to include 24 unreported KOGS symptoms, in a first male patient, the third overall associated with the PDGFRB c.1751C>G p.(Pro584Arg) mutation. Eighteen of these symptoms are unique to our patient, the remaining six are shared with other patients. Of the 24 unreported features overall, 6 show marked phenotype evolution and varying time of onset. The triangular face detected at 14 months and long palpebral fissures with lateral ectropion at 4 years are present in other members of the cohort. The remaining 4 are unique to Patient 5: pronounced macrocephaly from birth, increasingly triangular anterior skull from 14 months, camptodactyly, emerging at 4 years and worsening joint contractures from 6 years. Compilation of all new symptoms reported here with published clinical data further identifies at least 18 clinical parameters common to all cases to date, encompassing both known KOGS-associated PDGFRB mutations. We therefore propose a set of 18 core KOGS symptoms, with 16 present in early childhood. These results should also impact diagnostic/prognostic scope, intervention and outcome potential for KOGS patients, particularly for developmentally progressive conditions such as scoliosis and myofibroma.

Keywords: Kosaki overgrowth syndrome; PDGFRB gene mutation; developmental progression; extended phenotype; rare genetic disorder; whole exome sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Exome / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Megalencephaly / genetics*
  • Megalencephaly / physiopathology
  • Musculoskeletal Abnormalities / genetics*
  • Musculoskeletal Abnormalities / physiopathology
  • Mutation
  • Phenotype
  • Receptor, Platelet-Derived Growth Factor beta / genetics*


  • PDGFRB protein, human
  • Receptor, Platelet-Derived Growth Factor beta