Phenotype expansion and development in Kosaki overgrowth syndrome.

TitlePhenotype expansion and development in Kosaki overgrowth syndrome.
Publication TypeJournal Article
Year of Publication2018
AuthorsGawliński, P, Pelc, M, Ciara, E, Jhangiani, S, Jurkiewicz, E, Gambin, T, Różdżyńska-Świątkowska, A, Dawidziuk, M, Coban-Akdemir, ZH, Guilbride, DL, Muzny, DM, Lupski, JR, Krajewska-Walasek, M
JournalClin Genet
Date Published2018 Apr
KeywordsAdolescent, Child, Child, Preschool, Exome, Female, Genetic Association Studies, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Male, Megalencephaly, Musculoskeletal Abnormalities, Mutation, Phenotype, Receptor, Platelet-Derived Growth Factor beta

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.

Alternate JournalClin Genet
PubMed ID29226947
Grant ListUM1 HG006542 / HG / NHGRI NIH HHS / United States

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