Understanding the phenotypic spectrum of ASXL-related disease: Ten cases and a review of the literature.


Journal

American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741

Informations de publication

Date de publication:
06 2021
Historique:
revised: 10 02 2021
received: 30 04 2020
accepted: 22 02 2021
pubmed: 23 3 2021
medline: 2 9 2021
entrez: 22 3 2021
Statut: ppublish

Résumé

Over the past decade, pathogenic variants in all members of the ASXL family of genes, ASXL1, ASXL2, and ASXL3, have been found to lead to clinically distinct but overlapping syndromes. Bohring-Opitz syndrome (BOPS) was first described as a clinical syndrome and later found to be associated with pathogenic variants in ASXL1. This syndrome is characterized by developmental delay, microcephaly, characteristic facies, hypotonia, and feeding difficulties. Subsequently, pathogenic variants in ASXL2 were found to lead to Shashi-Pena syndrome (SHAPNS) and in ASXL3 to lead to Bainbridge-Ropers syndrome (BRPS). While SHAPNS and BRPS share many core features with BOPS, there also seem to be emerging clear differences. Here, we present five cases of BOPS, one case of SHAPNS, and four cases of BRPS. By adding our cohort to the limited number of previously published patients, we review the overlapping features of ASXL-related diseases that bind them together, while focusing on the characteristics that make each neurodevelopmental syndrome unique. This will assist in diagnosis of these overlapping conditions and allow clinicians to more comprehensively counsel affected families.

Identifiants

pubmed: 33751773
doi: 10.1002/ajmg.a.62156
pmc: PMC8842511
mid: NIHMS1775327
doi:

Substances chimiques

ASXL1 protein, human 0
ASXL2 protein, human 0
ASXL3 protein, human 0
Repressor Proteins 0
Transcription Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1700-1711

Subventions

Organisme : NICHD NIH HHS
ID : P50 HD105354
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS082761
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS007413
Pays : United States

Informations de copyright

© 2021 Wiley Periodicals LLC.

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Auteurs

Vishnu Anand Cuddapah (VA)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Holly A Dubbs (HA)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
The Epilepsy Neurogenetics Initiative, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Laura Adang (L)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Steven L Kugler (SL)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Elizabeth M McCormick (EM)

Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Zarazuela Zolkipli-Cunningham (Z)

Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Departments of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Xilma R Ortiz-González (XR)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
The Epilepsy Neurogenetics Initiative, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Shana McCormack (S)

Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Elaine Zackai (E)

Departments of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Daniel J Licht (DJ)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Marni J Falk (MJ)

Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Departments of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Eric D Marsh (ED)

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
The Epilepsy Neurogenetics Initiative, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

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Classifications MeSH