Retinal disorders

Gene: DYRK1A

Green List (high evidence)

Comment on list classification: DYRK1A syndrome patients may present with vision abnormalities, including retinal involvement. There is sufficient evidence available (4 unrelated patients with a retinal phenotype) for the association of monoallelic DYRK1A variants with retinal disorders, which fits into the scope of this panel. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 29 Aug 2025, 10:23 a.m. | Last Modified: 29 Aug 2025, 10:23 a.m.

Panel Version: 8.14

As reviewed by Siying Lin, there are at least 4 different variants reported in 4 unrelated patients with DYRK1A syndrome where a retinal phenotype was noted:
PMID: 33159716 Meissner et al., 2020: Proband 1 – Female; non-consanguineous parents. Ocular phenotype: tortuous retinal vessels, bilateral anomalous optic nerves with increased cup‐to‐disc ratio, and mild hyperopic astigmatism. Heterozygous for DYRK1A c.201_204del, p.(Asn68fs) - de novo.
PMID: 36736451 Cai et al., 2023: Case study - Female, 4 y.o. Found to have retinopathy on fundus examination. Heterozygous for DYRK1A c.1370_1373dupTAAG, p.(?) – de novo.
PMID: 40405340 Lin et al., 2025: Two individuals from unrelated Bengali families presented with familial exudative vitreoretinopathy (FEVR)-like presentations. They were heterozygous for a de novo DYRK1A variant each: c.1282C>T, p.(Arg428Ter) and c.857T>C; p.(Leu286Pro) .
Functional studies: DYRK1A has been linked to retinal development in mouse models (PMID: 19081073 Laguna et al., 2008). DYRK1A GeneReviews entry includes retinal anomalies as a feature of DYRK1A syndrome (https://www.ncbi.nlm.nih.gov/books/NBK333438/, accessed 15 Aug 2025). OMIM:614104 and Gene2Phenotype report an association with DYRK1A-related intellectual developmental disorder (accessed 15 Aug 2025).

Created: 29 Aug 2025, 10:22 a.m. | Last Modified: 29 Aug 2025, 10:22 a.m.

Panel Version: 8.14

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder, autosomal dominant 7, OMIM:614104; Retinal disorder, MONDO:0005283

Publications

• 33159716
• 36736451
• 40405340
• 19081073

Green List (high evidence)

PMID 36736451: one individual with DYRK1A syndrome and anomalous retinal vasculature.
PMID 40405340: two individuals with FEVR-like presentations and later likely disease-causing DKRY1A variants identified; the retinal phenotype can be the presenting feature of DYRK1A syndrome
Sources: Literature

Created: 25 May 2025, 9:10 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
FEVR

Publications

• PMID: 40405340
• 36736451

Mode of pathogenicity
Other