Ocular Phenotype Associated with DYRK1A Variants

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Ophthalmology

Background:

• DYRK1A (Dual-specificity tyrosine phosphorylation-regulated kinase 1A) plays a critical role in central nervous system development.
• DYRK1A gene variations are associated with Down syndrome and DYRK1A-related intellectual disability syndrome, characterized by intellectual disability, autism, and specific facial features.
• Preclinical and case studies suggest a link between DYRK1A and ocular development, with reported ocular pathologies.

Purpose of the Study:

• To investigate the prevalence and spectrum of ocular abnormalities in patients with pathogenic variants in the DYRK1A gene.
• To determine the frequency of ocular features in individuals diagnosed with DYRK1A-related intellectual disability syndrome.

Main Methods:

• A study combining self-reported data from DYRK1A Syndrome International Association families, molecularly confirmed cases, and literature review.
• Analysis of ocular features in a cohort of 145 patients with heterozygous DYRK1A variants.
• Categorization and quantification of reported ocular abnormalities including optic nerve hypoplasia, refractive errors, and strabismus.

Main Results:

• Ocular features were identified in 62.1% (90/145) of patients with heterozygous DYRK1A variants.
• The most common ocular findings included refractive error (35.6%), strabismus (21.1%), and optic nerve hypoplasia (13%).
• Data was aggregated from 26 self-reporting families, 19 UK Genomics England participants, and 112 literature-reported patients.

Conclusions:

• Heterozygous pathogenic variants in DYRK1A are frequently associated with a range of ocular abnormalities.
• Routine ophthalmological evaluation is recommended for patients with DYRK1A variants to prevent amblyopia and manage visual comorbidities.
• Addressing visual impairments is essential for optimizing learning, behavior, and overall quality of life in individuals with DYRK1A-related disorders.