Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2020 Jul;98(1):19-31.
doi: 10.1111/cge.13752. Epub 2020 May 4.

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

Alison Foster  1   2 , Basile Chalot  3   4   5 , Thalia Antoniadi  6 , Elise Schaefer  7 , Rebecca Keelagher  6 , Gavin Ryan  6 , Quentin Thomas  8 , Christophe Philippe  4   5 , Ange-Line Bruel  4   5 , Arthur Sorlin  3   4   5 , Christel Thauvin-Robinet  3   4   5 , Marc Bardou  9   10 , Maxime Luu  9   10 , Veronique Quenardelle  11 , Valerie Wolff  11   12 , Jessica Woodley  6 , Pierre Vabres  13 , Derek Lim  2 , Rebecca Igbokwe  2 , Annie Joseph  14 , Harriet Walker  15 , Andrea Jester  15 , Jonathan Ellenbogen  16 , Diana Johnson  17 , Bethanie Rooke  18 , Celia Moss  1   18 , Trevor Cole  2 , Laurence Faivre  3   5
Affiliations
Case Reports

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

Alison Foster et al. Clin Genet. 2020 Jul.

Abstract

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.

Keywords: PDGFRB; KOGS; Kosaki overgrowth syndrome; fusiform aneurysm; long-term outcome; vascular.

PubMed Disclaimer

References

REFERENCES

    1. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276-1312. https://doi.org/10.1101/gad.1653708.
    1. Cheung YH, Gayden T, Campeau PM, et al. A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet. 2013;92(6):996-1000. https://doi.org/10.1016/j.ajhg.2013.04.026.
    1. Martignetti JA, Tian L, Li D, et al. Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet. 2013;92(6):1001-1007. https://doi.org/10.1016/j.ajhg.2013.04.024.
    1. Lepelletier C. Heterozygous PDGFRB mutation in a three-generation family with autosomal dominant infantile Myofibromatosis. Acta Derm Venereol. 2017;97:858-859. https://doi.org/10.2340/00015555-2671.
    1. Murray N, Hanna B, Graf N, et al. The spectrum of infantile myofibromatosis includes both non-penetrance and adult recurrence. Eur J Med Genet. 2017;60(7):353-358. https://doi.org/10.1016/j.ejmg.2017.02.005.

Publication types

Substances

LinkOut - more resources