Language
English
Publication Date
6-1-2026
Journal
Clinical Genetics
DOI
10.1111/cge.70155
PMID
41736477
PMCID
PMC13167628
PubMedCentral® Posted Date
2-24-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Dandy-Walker malformation (DWM) is a rare congenital abnormality of the posterior fossa and the cerebellum and has an incidence of 1 in 10 000 to 30 000 births. Although DWM can present in isolation, it is often associated with other central nervous system (CNS) abnormalities or extra-CNS anomalies (DWM+). A molecular cause is not identified in the majority of individuals with DWM+. This is due, in part, to uncertainty regarding optimal testing strategies and an incomplete understanding of the genetic causes of DWM+. In this study, we analyzed clinical exome sequencing (cES) data from 91 individuals with DWM+ to determine its diagnostic efficacy. A definitive or probable diagnosis was made for 32 individuals, yielding a diagnostic rate of 35.2% (32/91). Commercially available brain malformation panels would have detected only 24.2% (8/33) to 54.5% (18/33) of the diagnoses made by cES. We then used data from our cohort, published cases, and mouse models to identify nine phenotypic expansions involving DWM. Our results suggest that cES should be considered for all individuals with DWM+ for whom a molecular diagnosis has not been established and that additional testing to identify a genetic cause of DWM is likely not warranted in individuals with genetic syndromes caused by variants in ANKRD11, C2CD3, COL4A1, KMT2D, KRAS, OPHN1, SHOC2, SMARCB1, and WDR73.
Keywords
Humans, Dandy-Walker Syndrome, Exome Sequencing, Phenotype, Female, Male, Animals, Cerebellum, Exome, Mice, Mutation, Child, Child, Preschool, cerebellum, Dandy‐Walker malformation, exome sequencing, gene panels, phenotypic expansions
Published Open-Access
yes
Recommended Citation
Araji, Sarah; Zhao, Xiaonan; Rosenfeld, Jill A; et al., "Non-Isolated Dandy-Walker Malformation: Exome Sequencing Efficacy and Phenotypic Expansions" (2026). Faculty, Staff and Students Publications. 7350.
https://digitalcommons.library.tmc.edu/baylor_docs/7350