%0 Journal Article %J Clin Genet %D 2018 %T Phenotype expansion and development in Kosaki overgrowth syndrome. %A Gawliński, P %A Pelc, M %A Ciara, E %A Jhangiani, S %A Jurkiewicz, E %A Gambin, T %A Różdżyńska-Świątkowska, A %A Dawidziuk, M %A Coban-Akdemir, Z H %A Guilbride, D L %A Donna M Muzny %A Lupski, J R %A Krajewska-Walasek, M %K Adolescent %K Child %K Child, Preschool %K Exome %K Female %K Genetic Association Studies %K Genetic Predisposition to Disease %K High-Throughput Nucleotide Sequencing %K Humans %K Male %K Megalencephaly %K Musculoskeletal Abnormalities %K Mutation %K Phenotype %K Receptor, Platelet-Derived Growth Factor beta %X

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.

%B Clin Genet %V 93 %P 919-924 %8 2018 Apr %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/29226947?dopt=Abstract %R 10.1111/cge.13192