All reported patients with SKDEAS have had a heterozygous de novo variant in WDR26 (NM_025160.6). Mutations are typically loss of function and have included frameshift, nonsense, splice site and full or partial gene deletions mutations that occur throughout the gene. A few individuals have been noted with de novo missense mutations in the CTLH domain that are predicted to alter protein function.
All reported individuals have been identified via exome sequencing, though targeted gene analysis could be utilized if there is high suspicion for the condition. In addition haploinsufficiency of WDR26 is suspected to contribute to the pathology of 1q41q42 microdeletion syndrome, particularly in regards to the neurocognitive and facial phenotype. Therefore, deletions of the gene are anticipated to present similarly, though isolated WDR26 deletions have not been reported.