Axenfeld-Rieger syndrome: more than meets the eye
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F23%3A10445441" target="_blank" >RIV/00216208:11130/23:10445441 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10445441 RIV/00064203:_____/23:10445441 RIV/00064165:_____/23:10445441
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Nal0yUM49G" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Nal0yUM49G</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1136/jmg-2022-108646" target="_blank" >10.1136/jmg-2022-108646</a>
Alternative languages
Result language
angličtina
Original language name
Axenfeld-Rieger syndrome: more than meets the eye
Original language description
BACKGROUND: Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition. METHODS: Genetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses. RESULTS: 128 individuals with causative variants in PITX2 or FOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for FOXC1-related ARS. Systemic anomalies were seen in all individuals with PITX2-related ARS and the majority of those with FOXC1-related ARS. PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype of FOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS. CONCLUSION: Since clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, PITX2-related ARS or FOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30101 - Human genetics
Result continuities
Project
<a href="/en/project/NV19-06-00189" target="_blank" >NV19-06-00189: Genetic factors of progressive hearing loss of cochlear implantation candidates: a potential for stratification of their therapy</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medical Genetics
ISSN
0022-2593
e-ISSN
1468-6244
Volume of the periodical
60
Issue of the periodical within the volume
4
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
368-379
UT code for WoS article
000831307900001
EID of the result in the Scopus database
2-s2.0-85135137847