Two Novel Variants of WDR26 in Chinese Patients with Intellectual Disability

Area of Science:

• Genetics
• Neurology

Background:

• Skraban-Deardorff syndrome is a rare autosomal dominant genetic disorder.
• It is caused by pathogenic variants in the WDR26 gene.

Observation:

• Two Chinese patients with Skraban-Deardorff syndrome were identified.
• They presented with novel de novo, heterozygous pathogenic WDR26 variants: c.977delA (p.N326Ifs*2) and c.1020-2A>G (p.R340Sfs*29).
• Clinical features included intellectual disability, developmental delay, and abnormal facial features, notably without early-onset seizures.

Findings:

• The identified variants expand the known phenotype spectrum of Skraban-Deardorff syndrome.
• Key diagnostic features include developmental delay (especially speech), rounded palpebral fissures, depressed nasal root, full nasal tip, and abnormal gums.
• WDR26 variants and 1q41q42 deletions are significant in the differential diagnosis of intellectual disability with distinct facial features.

Implications:

• This research refines the diagnostic criteria for Skraban-Deardorff syndrome.
• It highlights the importance of considering WDR26 gene variants in individuals with intellectual disability and specific facial dysmorphisms.
• Further research into WDR26-related disorders is warranted to understand the full spectrum of clinical presentations and underlying mechanisms.