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Phenotypic expansion of POGZ ‐related intellectual disability syndrome (White‐Sutton syndrome)
Author(s) -
Assia Batzir Nurit,
Posey Jennifer E.,
Song Xiaofei,
Akdemir Zeynep Coban,
Rosenfeld Jill A.,
Brown Chester W.,
Chen Emily,
Holtrop Shan G.,
Mizerik Elizabeth,
Nieto Moreno Margarita,
Payne Katelyn,
RaasRothschild Annick,
Scott Richard,
Ver Hilary J.,
Zadeh Neda,
Lupski James R.,
Sutton V. Reid
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61380
Subject(s) - intellectual disability , microcephaly , autism spectrum disorder , medicine , medical genetics , pediatrics , exome sequencing , population , obstructive sleep apnea , autism , genetics , phenotype , biology , psychiatry , environmental health , gene
Abstract White‐Sutton syndrome (WHSUS) is a recently‐identified genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ . Thus far, over 50 individuals have been reported worldwide, however phenotypic characterization and data regarding the natural history are still incomplete. Here we report the clinical features of 22 individuals with 21 unique loss of function POGZ variants. We observed a broad spectrum of intellectual disability and/or developmental delay with or without autism, and speech delay in all individuals. Other common problems included ocular abnormalities, hearing loss and gait abnormalities. A validated sleep disordered breathing questionnaire identified symptoms of obstructive sleep apnea in 4/12 (33%) individuals. A higher‐than‐expected proportion of cases also had gastrointestinal phenotypes, both functional and anatomical, as well as genitourinary anomalies. In line with previous publications, we observed an increased body mass index (BMI) z‐score compared to the general population (mean 0.59, median 0.9; p 0.0253). Common facial features included microcephaly, broad forehead, midface hypoplasia, triangular mouth, broad nasal root and flat nasal bridge. Analysis of the Baylor Genetics clinical laboratory database revealed that POGZ variants were implicated in approximately 0.14% of cases who underwent clinical exome sequencing for neurological indications with or without involvement of other body systems. This study describes a greater allelic series and expands the phenotypic spectrum of this new syndromic form of intellectual disability and autism.