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

Phenotype expansion and development in Kosaki overgrowth syndrome.

Author information

1
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
2
Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
3
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
4
Department of Diagnostic Imaging, The Children's Memorial Health Institute, Warsaw, Poland.
5
Institute of Computer Science, Warsaw University of Technology, Warsaw, Texas.
6
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
7
Anthropology Laboratory, Children's Memorial Health Institute, Warsaw, Poland.
8
Texas Children's Hospital, Houston, Texas.

Abstract

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

PMID:
29226947
DOI:
10.1111/cge.13192

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