Clinical and Genotype-Phenotype Investigation of the Neurofibromatosis Type 1 Paediatric Population in Hungary, Diagnostic and Follow-up Protocols
Veres Klára
Health Sciences
Dr. Nagy Zoltán Zsolt
SE Bőr-, Nemikórtani és Bőronkológiai Klinika előadóterme
2026-02-02 13:30:00
Clinical and comparative health sciences
Dr. Nagy Zoltán Zsolt
Dr. Szabó László és Dr. Szalai Zsuzsanna
Dr. Bánvölgyi András
Dr. Harangi Ferenc
Dr. Holló Péter
Dr. Rosdy Beáta
Dr. Lőrincz Kende Kálmán
This doctoral work addressed three hypotheses: (1) that the clinical spectrum of the Hungarian paediatric NF1 population is largely comparable to that of international cohorts; (2) that genotype–phenotype associations reveal mutation-specific severity patterns; and (3) that these findings enable the development of an age-adapted follow-up protocol.
Hypothesis 1 was partly supported: the Hungarian paediatric NF1 cohort showed a generally similar clinical profile to international data, with age-related patterns following comparable trends. Café-au-lait macules were almost universal, while freckling, cutaneous neurofibromas, Lisch nodules, and cognitive and behavioural disturbances appeared later and somewhat less frequently. In contrast, the occurrence of plexiform neurofibromas, optic pathway gliomas and skeletal manifestations closely matched international findings. Minor discrepancies may partly reflect the retrospective design and potential underdetection.
Hypothesis 2 was also supported: splice-site variants were associated with disproportionately severe phenotypes (skeletal, intracranial abnormalities, plexiform neurofibromas, Lisch nodules, pseudarthrosis), while microdeletions conferred the most severe multisystemic involvement, and missense variants milder profiles. These tendencies point to aberrant splicing and modifier genes as possible mechanisms but require larger studies.
Hypothesis 3 was realised in a structured, multidisciplinary, age-adapted follow-up protocol integrating clinical trajectories, genetic categories, and international recommendations, aiming to improve diagnostic accuracy, early complication detection, and personalised care.
In conclusion, this thesis provides the first integrated dataset on paediatric NF1 in Hungary, reveals variant-associated severity patterns, and proposes a clinically applicable protocol, laying the groundwork for prospective multicentre research and precision medicine.
