WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome

Clin Genet. 2018 Feb;93(2):360-364. doi: 10.1111/cge.13054.

J Suleiman ¹, D Allingham-Hawkins ², M Hashem ³, H E Shamseldin ³, F S Alkuraya ³ ⁴ ⁵, A W El-Hattab ⁶

Affiliations

1 Division of Neurology, Department of Pediatrics, Tawam Hospital, Al-Ain, United Arab Emirates.
2 PreventionGenetics, LLC, Marshfield, Wisconsin, USA.
3 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
4 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
5 Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
6 Division of Genetic and Metabolic Disorders, Department of Pediatrics, Tawam Hospital, Al-Ain, United Arab Emirates.

PMID: 28503735 DOI: 10.1111/cge.13054

Abstract

The advancement in genomic Sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic Sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.

Keywords

WDR45B; epilepsy; intellectual disability; quadriplegia; spasticity.

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