Introduction

This study evaluated the clinical utility of proband-only whole-exome sequencing (WES) in paediatric and young adult patients with atypical or complex haematologic and oncologic presentations suggestive of an underlying genetic aetiology.

Material and methods

We retrospectively analysed 30 patients treated at a single paediatric oncology and haematology center. Peripheral blood- derived DNA underwent WES, followed by phenotype-driven variant prioritisation and classification according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria. Clinical implications were assessed with respect to diagnosis, genetic counselling, surveillance, and treatment modification.

Results

Causal findings were identified in 6 patients (20%), and causal or likely causal findings in 9 patients (30%). Clinically relevant implications included genetic counselling in 8 patients (26.7%), treatment adjustment in 4 patients (13.3%), and surveillance in 4 patients (13.3%). Diagnostic benefit was greatest in patients with cyto- penias and selected haematologic malignancies, whereas no causal findings were detected in the solid tumour subgroup. Interpretation was limited by the proband-only design, lack of routine segregation testing, and use of blood-derived DNA in oncologic patients.

Conclusions

Whole-exome sequencing may contribute to diagnosis and clinical decision-making in carefully selected paediatric haematology patients with atypical manifestations or suspected hereditary disorders. Larger prospective studies incorporating clinical outcomes, cost-effectiveness analyses, and long-term follow-up are needed to define its role in routine paediatric oncohematologic practice.