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Kosaki overgrowth syndrome: A novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications
Author(s) -
Foster Alison,
Chalot Basile,
Antoniadi Thalia,
Schaefer Elise,
Keelagher Rebecca,
Ryan Gavin,
Thomas Quentin,
Philippe Christophe,
Bruel AngeLine,
Sorlin Arthur,
ThauvinRobinet Christel,
Bardou Marc,
Luu Maxime,
Quenardelle Veronique,
Wolff Valerie,
Woodley Jessica,
Vabres Pierre,
Lim Derek,
Igbokwe Rebecca,
Joseph Annie,
Walker Harriet,
Jester Andrea,
Ellenbogen Jonathan,
Johnson Diana,
Rooke Bethanie,
Moss Celia,
Cole Trevor,
Faivre Laurence
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13752
Subject(s) - medicine , camptodactyly , craniosynostosis , ptosis , short stature , ehlers–danlos syndrome , pdgfrb , noonan syndrome , pathology , surgery , genetics , gene , biology
Heterozygous activating variants in platelet‐derived growth factor, beta ( PDGFRB ) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long‐term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contractures, camptodactyly, widely spaced teeth, and constriction rings. We also propose novel occasional features including craniosynostosis, ocular pterygia, anterior chamber cleavage syndrome, early osteoporosis, increased pigmentation, recurrent haematomas, predisposition to cellulitis, nail dystrophy, carpal tunnel syndrome, recurrent hypoglycaemia in infancy, joint dislocation, and splenomegaly. Importantly, we report fusiform aneurysm of the basilar artery in two patients. Complications include thrombosis and stroke in the oldest reported patient and fatal rupture at the age of 21 in the patient with the novel variant. We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS‐like disorders and suggest vascular imaging is indicated in these patients.