Two remarkable cases of haploinsufficiency found in the DYRK1A gene.

Introduction: DYRK1A syndrome, also known as "Intellectual developmental disorder, autosomal dominant 7," is a syndromic intellectual disability characterized by dysmorphic features including deep-set eyes, prominent ears, and retrognathia. Patients have neurodevelopmental problems, ocular anomalies, and multisystem phenotypes. Most cases result from single nucleotide variants causing DYRK1A-haploinsufficiency, while deletions occur in < 15% of cases. This study discusses two patients with DYRK1A haploinsufficiency.

Case presentation: Patient 1 had a novel early termination codon variant in DYRK1A and Patient 2 had partial monosomy 21/monosomy 21 mosaicism, both de novo occurrences. Genetic analysis revealed that Patient 2 had DYRK1A monosomy in all cells, and dysmorphic investigations suggested facial features were more likely caused by DYRK1A-haploinsufficiency rather than by mosaic monosomy 21.

Conclusion: This study is the first to describe a patient with a complex chromosomal condition leading to DYRK1A haploinsufficiency, thereby expanding the known genotype spectrum of the syndrome.