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Am J Med Genet A. 2020 Jan;182(1):38-52. doi: 10.1002/ajmg.a.61380. Epub 2019 Nov 29.

Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome).

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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Texas Children's Hospital, Houston, Texas.
Le Bonheur Children's Hospital, Memphis, Tennessee.
Division of Medical Genetics, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
Department of Genetics, Kaiser Permanente, San Francisco, California.
Division of Clinical and Translational Genetics, Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, Florida.
Jackson Memorial Hospital, Miami, Florida.
Section of Child Neurology, Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana.
Institute of Rare Diseases & Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel.
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Clinical Genetics Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK.
Division of Neurogenetics, Department of Neurology, Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland.
Genetics Center, Orange, California.
Division of Medical Genetics, Children's Hospital of Orange County, Orange, California.
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.


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.


POGZ; autism; developmental delay; intellectual disability; speech delay


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