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

Baylor-Hopkins Center for Mendelian Genomics

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)38-52
Number of pages15
JournalAmerican Journal of Medical Genetics, Part A
Volume182
Issue number1
DOIs
StatePublished - Jan 1 2020

Fingerprint

Autistic Disorder
Nose
Intellectual Disability
Eye Abnormalities
Exome
Language Development Disorders
Microcephaly
Inborn Genetic Diseases
Forehead
Sleep Apnea Syndromes
Obstructive Sleep Apnea
Natural History
Gait
Hearing Loss
Mouth
Body Mass Index
Databases
Phenotype
Population
Surveys and Questionnaires

Keywords

  • autism
  • developmental delay
  • intellectual disability
  • POGZ
  • speech delay

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome). / Baylor-Hopkins Center for Mendelian Genomics.

In: American Journal of Medical Genetics, Part A, Vol. 182, No. 1, 01.01.2020, p. 38-52.

Research output: Contribution to journalArticle

@article{4c6f1f527e664cf78b4fba9739041087,
title = "Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome)",
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.",
keywords = "autism, developmental delay, intellectual disability, POGZ, speech delay",
author = "{Baylor-Hopkins Center for Mendelian Genomics} and {Assia Batzir}, Nurit and Posey, {Jennifer E.} and Xiaofei Song and Akdemir, {Zeynep Coban} and Rosenfeld, {Jill A.} and Brown, {Chester W.} and Emily Chen and Holtrop, {Shannon G.} and Elizabeth Mizerik and {Nieto Moreno}, Margarita and Katelyn Payne and Annick Raas-Rothschild and Richard Scott and Vernon, {Hilary J.} and Neda Zadeh and Lupski, {James R.} and Sutton, {V. Reid}",
year = "2020",
month = "1",
day = "1",
doi = "10.1002/ajmg.a.61380",
language = "English (US)",
volume = "182",
pages = "38--52",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome)

AU - Baylor-Hopkins Center for Mendelian Genomics

AU - Assia Batzir, Nurit

AU - Posey, Jennifer E.

AU - Song, Xiaofei

AU - Akdemir, Zeynep Coban

AU - Rosenfeld, Jill A.

AU - Brown, Chester W.

AU - Chen, Emily

AU - Holtrop, Shannon G.

AU - Mizerik, Elizabeth

AU - Nieto Moreno, Margarita

AU - Payne, Katelyn

AU - Raas-Rothschild, Annick

AU - Scott, Richard

AU - Vernon, Hilary J.

AU - Zadeh, Neda

AU - Lupski, James R.

AU - Sutton, V. Reid

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - autism

KW - developmental delay

KW - intellectual disability

KW - POGZ

KW - speech delay

UR - http://www.scopus.com/inward/record.url?scp=85075740438&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075740438&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.61380

DO - 10.1002/ajmg.a.61380

M3 - Article

C2 - 31782611

AN - SCOPUS:85075740438

VL - 182

SP - 38

EP - 52

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 1

ER -