Further delineation of the clinical spectrum of White-Sutton syndrome: 12 new individuals and a review of the literature

Murch, Oliver, Jain, Vani, Benneche, Andreas, Metcalfe, Kay, Hobson, Emma, Prescott, Katrina, Chandler, Kate, Ghali, Neeti, Carmichael, Jenny, Foulds, Nicola C., Paulsen, Julie, Smeland, Marie F., Berland, Siren and Fry, Andrew E. ORCID: https://orcid.org/0000-0001-9778-6924 2022. Further delineation of the clinical spectrum of White-Sutton syndrome: 12 new individuals and a review of the literature. European Journal of Human Genetics 30 , pp. 95-100. 10.1038/s41431-021-00961-3

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Abstract

White–Sutton syndrome (WHSUS) is a neurodevelopmental disorder caused by heterozygous loss-of-function variants in POGZ. Through the Deciphering Developmental Disorders study and clinical testing, we identified 12 individuals from 10 families with pathogenic or likely pathogenic variants in POGZ (eight de novo and two inherited). Most individuals had delayed development and/or intellectual disability. We analyzed the clinical findings in our series and combined it with data from 89 previously reported individuals. The results demonstrate WHSUS is associated with variable developmental delay or intellectual disability, increased risk of obesity, visual defects, craniofacial dysmorphism, sensorineural hearing loss, feeding problems, seizures, and structural brain malformations. Our series includes further individuals with rod-cone dystrophy, cleft lip and palate, congenital diaphragmatic hernia, and duplicated renal drainage system, suggesting these are rare complications of WHSUS. In addition, we describe an individual with a novel, de novo missense variant in POGZ and features of WHSUS. Our work further delineates the phenotypic spectrum of WHSUS highlighting the variable severity of this disorder and the observation of familial pathogenic POGZ variants.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer Nature
ISSN:	1018-4813
Date of First Compliant Deposit:	6 December 2021
Date of Acceptance:	7 September 2021
Last Modified:	07 Nov 2023 04:45
URI:	https://orca.cardiff.ac.uk/id/eprint/145954

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