Lekárska genetika a diagnostika 2/2026

Two genetic diagnosis in patients with neurodevelopmental disorders

Purpose: Number of patients with multiple genetics diagnoses arised using the whole-exome and whole-genome sequencing in genetic diagnostics. In large cohorts of patients undergoing whole-exome sequencing, those with dual or multiple diagnoses account for 2.6–5% of the total number of tested patients.

Case reports: We present case reports of patients with two genetic diagnoses contributing to blended phenotype. The first case report describes a boy with a neurodevelopmental disorder in whom we confirmed Coffin-Siris syndrome and a KDM5C-associated neurodevelopmental disorder. The second case report focuses on a family with 2q23.1 microduplication syndrome and an EIF3F-associated intellectual developmental disorder.

Conclusion: Multiple genetic diagnoses in the same patient can lead to two distinct phenotypes, a blended or an indistinguishable phenotype. Mutated genes may interact synergistically or antagonistically, leading to a milder or more extreme phenotype, or to the development of atypical phenotype. A second genetic diagnosis sometimes can be a cause of an atypical phenotypic presentation of a known familial disorder. Knowledge of all the patient‘s diagnoses is crucial for appropriate patient management.

Keywords: multiple genetic diagnoses, neurodevelopmental disorders, ARID1B, KDM5C, 2q23.1 mikroduplication syndrome, EIF3F