AXIN2-related oligodontia-colorectal cancer syndrome with cleft palate as a possible new feature.
AXIN2
cancer predisposition syndrome
cleft palate
oligodontia
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
30
12
2022
received:
02
08
2022
accepted:
09
02
2023
medline:
15
6
2023
pubmed:
3
3
2023
entrez:
2
3
2023
Statut:
ppublish
Résumé
Pathogenic variants in AXIN2 have been associated with tooth agenesis, colon polyps, and colon cancer. Given the rare nature of this phenotype, we set out to collect additional genotypic and phenotypic information. Data were collected via a structured questionnaire. Sequencing was performed in these patients mostly due to diagnostic purpose. A little more than half of the AXIN2 variant carriers were identified by NGS; other six were family members. Here, we report 13 individuals with a heterozygous AXIN2 pathogenic/likely pathogenic variant who have a variable expression of oligodontia-colorectal cancer syndrome (OMIM 608615) or oligodontia-cancer predisposition syndrome (ORPHA 300576). Three individuals from one family also had cleft palate, which might represent a new clinical feature of AXIN2 phenotype, also given the fact that AXIN2 polymorphisms have been found in association with oral clefting in population studies. AXIN2 has already been added to multigene cancer panel tests; further research should be conducted to determine whether it should be added to cleft lip/palate multigene panels. More clarity about oligodontia-colorectal cancer syndrome, about the variable expression, and associated cancer risks is needed to improve clinical management and to establish guidelines for surveillance. We collected information about the surveillance that was advised, which might support clinical management of these patients.
Sections du résumé
BACKGROUND
Pathogenic variants in AXIN2 have been associated with tooth agenesis, colon polyps, and colon cancer. Given the rare nature of this phenotype, we set out to collect additional genotypic and phenotypic information.
METHODS
Data were collected via a structured questionnaire. Sequencing was performed in these patients mostly due to diagnostic purpose. A little more than half of the AXIN2 variant carriers were identified by NGS; other six were family members.
RESULTS
Here, we report 13 individuals with a heterozygous AXIN2 pathogenic/likely pathogenic variant who have a variable expression of oligodontia-colorectal cancer syndrome (OMIM 608615) or oligodontia-cancer predisposition syndrome (ORPHA 300576). Three individuals from one family also had cleft palate, which might represent a new clinical feature of AXIN2 phenotype, also given the fact that AXIN2 polymorphisms have been found in association with oral clefting in population studies. AXIN2 has already been added to multigene cancer panel tests; further research should be conducted to determine whether it should be added to cleft lip/palate multigene panels.
CONCLUSION
More clarity about oligodontia-colorectal cancer syndrome, about the variable expression, and associated cancer risks is needed to improve clinical management and to establish guidelines for surveillance. We collected information about the surveillance that was advised, which might support clinical management of these patients.
Identifiants
pubmed: 36860143
doi: 10.1002/mgg3.2157
pmc: PMC10265056
doi:
Substances chimiques
AXIN2 protein, human
0
Axin Protein
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
e2157Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009141
Pays : United States
Informations de copyright
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):169-73
pubmed: 18683894
J Dent Res. 2012 May;91(5):473-8
pubmed: 22370446
Development. 2018 Feb 21;145(4):
pubmed: 29437780
Am J Hum Genet. 2004 May;74(5):1043-50
pubmed: 15042511
Semin Cell Dev Biol. 2010 May;21(3):309-13
pubmed: 19747977
Nat Genet. 2000 Oct;26(2):146-7
pubmed: 11017067
Fam Cancer. 2019 Jul;18(3):311-315
pubmed: 30671715
Cancer Lett. 2014 Dec 1;355(1):1-8
pubmed: 25236910
Dev Biol. 2009 Jul 1;331(1):38-49
pubmed: 19394325
Hered Cancer Clin Pract. 2020 Jul 30;18:14
pubmed: 32754288
BMC Med Genet. 2020 Aug 17;21(1):161
pubmed: 32807118
Neuro Endocrinol Lett. 2017 Jul;38(3):131-137
pubmed: 28759178
Mol Genet Genomic Med. 2023 Jun;11(6):e2157
pubmed: 36860143
J Med Genet. 2006 Feb;43(2):138-42
pubmed: 15831593