TY - JOUR
T1 - Kosaki overgrowth syndrome
T2 - A novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications
AU - Foster, Alison
AU - Chalot, Basile
AU - Antoniadi, Thalia
AU - Schaefer, Elise
AU - Keelagher, Rebecca
AU - Ryan, Gavin
AU - Thomas, Quentin
AU - Philippe, Christophe
AU - Bruel, Ange-Line
AU - Sorlin, Arthur
AU - Thauvin-Robinet, Christel
AU - Bardou, Marc
AU - Luu, Maxime
AU - Quenardelle, Veronique
AU - Wolff, Valerie
AU - Woodley, Jessica
AU - Vabres, Pierre
AU - Lim, Derek
AU - Igbokwe, Rebecca
AU - Joseph, Annie
AU - Walker, Harriet
AU - Jester, Andrea
AU - Ellenbogen, Jonathan
AU - Johnson, Diana
AU - Rooke, Bethanie
AU - Moss, Celia
AU - Cole, Trevor
AU - Faivre, Laurence
N1 - © 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
PY - 2020/4/14
Y1 - 2020/4/14
N2 - 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.
AB - 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.
KW - KOGS
KW - Kosaki overgrowth syndrome
KW - PDGFRB
KW - fusiform aneurysm
KW - long-term outcome
KW - vascular
UR - http://www.scopus.com/inward/record.url?scp=85085064551&partnerID=8YFLogxK
U2 - 10.1111/cge.13752
DO - 10.1111/cge.13752
M3 - Article
C2 - 32291752
SN - 0009-9163
VL - 98
SP - 19
EP - 31
JO - Clinical Genetics
JF - Clinical Genetics
IS - 1
ER -