Journal Article


Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

Abstract

Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, pediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ eight years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10-12. 

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Authors

Balasubramanian M
Dingemans AJM
lbaba S
Richardson R
Yates TM
Cox H
Douzgou S
Armstrong R
Sansbury FH
Burke KB
Fry AE
Ragge N
Sharif S
Foster A
De Sandre-Giovannoli A
Elouej S
Vasudevan P
Mansour S
Wilson K
Stewart H
Heide S
Nava C
Keren B
Demirdas S
Brooks AS
Vincent M
Isidor B
Küry S
Schouten M
Leenders E
Chung WK
van Haeringen A
Scheffner T
Debray F
White SM
Valenzuela Palafoll MI
Pfundt R
Newbury-Ecob R
Kleefstra T

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year of publication: 2021
Date of RADAR deposit: 2020-10-22


Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License


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