Epidemiologic, Clinical, and Molecular Landscape of Neurofibromatosis Type 1 in Oman: A Study of 211 Individuals

Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder caused by NF1 variants that disrupt neurofibromin regulation of the Ras pathway, increasing tumor risk. Despite the global recognition, data from the Middle East remain scarce with no large cohorts reported. This study investigates large cohort of NF1 patients in Oman.

A retrospective study was conducted to analyze the epidemiologic, clinical, and molecular data of NF1 patients followed at Sultan Qaboos University Hospital and Royal Hospital between 2010 and 2024.

A total of 211 NF1 patients were selected, 56% sporadic and 46% inherited, and 50% were diagnosed by the age of one year. Family history of NF1 and malignancy significantly correlated. Café-au-lait spots (86.3%) were the most common feature, followed by neurofibromas (41.7%), freckling (26.5%), and Lisch nodules (26%). Plexiform neurofibroma was identified in 19% of patients. Optic gliomas were mostly seen in children (17.5%). Cognitive impairment (20.9%) was significantly associated with seizures (10.4%; P = 0.018). Malignancy was noted in 10.9% of cases, most commonly malignant peripheral nerve sheath tumors (34.8%), followed by breast cancer (17.4%). Hypertension was seen in 5.7%. Among the sixty-seven patients who were genetically tested, 80.5% had NF1 variants, mostly deletions (27.8%), without genotype-phenotype correlation.

This represents the first and largest NF1 cohort report from Oman and the region demonstrating the demographic, phenotypic, and genotypic variability of NF1, emphasizing the consistency of NF1 phenotype globally and addressing the risk of malignancy and other complications. While NF1 is primarily a clinical diagnosis, molecular testing supports diagnostic accuracy, genetic counseling, and prevention, especially with a high percentage of familial cases, and emphasizes the importance of long-term surveillance and multidisciplinary care.