Lekárska genetika a diagnostika 1/2026
Reinterpretation of the primary indication in the context of secondary symptoms using a whole-exome approach in a patient with cardiofaciocutaneous syndrome
Objective/Introduction: Cardiofaciocutaneous syndrome (CFCS) is a syndromic disease caused by germline RAS/MAPK mutations, characterized by marked craniofacial dysmorphism, congenital heart defects, gastrointestinal dysfunction, skin abnormalities, neurocognitive disease, and epilepsy. New studies have linked the syndrome to hypoglobulin, but the comprehensive characterization of immunological abnormalities is not yet fully understood.
Case: A 2-year-old male proband was referred by a clinical geneticist for genetic analysis using WES analysis, namely for the analysis of a virtual panel of genes associated with immunodeficiency, due to the presence of recurrent febrile illnesses in his personal history, respiratory infections, and epilepsy, West syndrome, skin depigmentation, and cerebral palsy. The family history included cases of epilepsy in two paternal sisters and the paternal grandmother. Performing massive parallel sequencing using the WES approach, we did not identify any potential causal DNA variants in the primarily indicated panel, however, using a broader virtual panel of genes, we detected several potentially causal DNA variants in the BRAF, CFHR5, TSC2 and WFS1 genes. Segregation analysis of the mentioned variants has not yet been performed due to the poor social status of the family.
Conclusion: Early diagnosis of genetic diseases in syndromic patients leads to targeted dispensary care, and thus to personalized therapy at the level of currently available knowledge, but often also to determining the final diagnosis of the patient, as demonstrated in this paper.
Keywords: cardiofaciocutaneous syndrome (CFCS), BRAF gene, TSC2 gene, massive parallel sequencing, whole exome, case report
