Kosaki overgrowth syndrome: a novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications.

Fiche publication

Date publication

avril 2020

Journal

Clinical genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BARDOU Marc , Pr FAIVRE Laurence , Pr PHILIPPE Christophe , Pr VABRES Pierre , Pr THAUVIN-ROBINET Christel

Tous les auteurs :
Foster A, Chalot B, Antoniadi T, Schaefer E, Keelagher R, Ryan G, Thomas Q, Philippe C, Bruel AL, Sorlin A, Thauvin-Robinet C, Bardou M, Luu M, Quenardelle V, Wolff V, Woodley J, Vabres P, Lim D, Igbokwe R, Joseph A, Walker H, Jester A, Ellenbogen J, Johnson D, Rooke B, Moss C, Cole T, Faivre L

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32291752

Résumé

Heterozygous activating variants in PDGFRB (platelet-derived growth factor, beta) 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 a fatal rupture age 20 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. This article is protected by copyright. All rights reserved.