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.
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http://dx.doi.org/10.1111/cge.13192 | DOI Listing |
J Med Genet
August 2024
Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital. Medicine Genetics Group, Vall d'Hebron Research Institute, Barcelona, Spain
Background: Tatton-Brown-Rahman syndrome (TBRS) is a rare disorder, caused by heterozygous pathogenic variants, and first described in 2014. TBRS is characterised by overgrowth, intellectual disability, facial dysmorphism, hypotonia and musculoskeletal features, as well as neurological and psychiatric features. Cardiac manifestations have also been reported, mainly congenital malformations such as atrial septal defect, ventricular septal defect and cardiac valvular disease.
View Article and Find Full Text PDFJ Cell Mol Med
July 2022
Experimental Medicine Unit, De Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Penttinen syndrome is a rare progeroid disorder caused by mutations in platelet-derived growth factor (PDGF) receptor beta (encoded by the PDGFRB proto-oncogene) and characterized by a prematurely aged appearance with lipoatrophy, skin lesions, thin hair and acro-osteolysis. Activating mutations in PDGFRB have been associated with other human diseases, including Kosaki overgrowth syndrome, infantile myofibromatosis, fusiform aneurysms, acute lymphoblastic leukaemia and myeloproliferative neoplasms associated with eosinophilia. The goal of the present study was to characterize the PDGFRB p.
View Article and Find Full Text PDFMol Syndromol
February 2022
Department of Radiology, Great Ormond Street Hospital, London, United Kingdom.
Heterozygous activating missense variants of are associated with the phenotype of Kosaki overgrowth syndrome (KOGS). Here, we present a family including a father and 2 siblings with a novel variant, c.2567A>T (p.
View Article and Find Full Text PDFDevelopment
December 2021
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Autosomal dominant PDGFRβ gain-of-function mutations in mice and humans cause a spectrum of wasting and overgrowth disorders afflicting the skeleton and other connective tissues, but the cellular origin of these disorders remains unknown. We demonstrate that skeletal stem cells (SSCs) isolated from mice with a gain-of-function D849V point mutation in PDGFRβ exhibit colony formation defects that parallel the wasting or overgrowth phenotypes of the mice. Single-cell RNA transcriptomics with SSC-derived polyclonal colonies demonstrates alterations in osteogenic and chondrogenic precursors caused by PDGFRβD849V.
View Article and Find Full Text PDFClin Genet
January 2022
Department of Pediatrics, Donostia University Hospital, Donostia, Spain.
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