Understanding the Phenotypic Spectrum of ASXL-related Disease: Ten Cases and a Review of the Literature

Overview

Journal Am J Med Genet A

Specialty Genetics

Date 2021 Mar 22

PMID 33751773

Citations 9

Authors

Vishnu Anand Cuddapah

Holly A Dubbs

Laura Adang

Steven L Kugler

Elizabeth M McCormick

Zarazuela Zolkipli-Cunningham

Xilma R Ortiz-Gonzalez

Shana McCormack

Elaine Zackai

Daniel J Licht

Marni J Falk

Eric D Marsh

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

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Four heterozygous variants in identified with Bainbridge-Ropers syndrome and further dissecting published genotype-phenotype spectrum.

Ling S, Zhang Y, Li N, Tian S, Hu R, Zhang D Front Neurosci. 2024; 18:1456433.

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Pathogenic Germline Variants in Uveal Melanoma Driver and BAP1-Associated Genes in Finnish Patients with Uveal Melanoma.

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Identification of a de novo variant in the ASXL2 gene related to Shashi-Pena syndrome.

Zheng Y, Yang L, Niu M, Zhao S, Liang L, Wu Y Mol Genet Genomic Med. 2023; 11(11):e2251.

PMID: 37493007 PMC: 10655504. DOI: 10.1002/mgg3.2251.

A newborn with a pathogenic variant in ASXL2 expanding the phenotype of SHAPNS: a case report and literature review.

Yuan M, Shan Y, Xu F, Yang L, Sun C, Cheng R Transl Pediatr. 2023; 12(1):86-96.

PMID: 36798937 PMC: 9926125. DOI: 10.21037/tp-22-220.

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