Phenotype and Genotype of Saudi Pediatric Patients With Neurofibromatosis Type 1: A Seven-Year Multicenter Experience From Saudi Arabia

Background Neurofibromatosis type 1 (NF1) is a complex disorder. Genetics and environment might be attributed as the leading cause of NF1, which is characterized by multisystemic involvement. We aim to elaborate on Saudi children's NF1 phenotypes and genotypes. Methods This study was conducted in the Ministry of National Guard Health Affairs (MNGHA), Saudi Arabia including three tertiary hospitals, using a retrospective cohort method. Electronic charts were reviewed to extract the variables. All Saudi pediatric patients aged less than 18 with NF1 were included. Consecutive sampling was used due to the limited number of patients. Results The study included 160 patients (81 males) with an average age of 8.08 years. Also, 33 (20.6%) patients had cutaneous neurofibroma while 31 (19.4%) patients had plexiform neurofibromas. Iris lisch nodules were seen in 33.75%. Optic pathway glioma was seen in 29 (18%) cases while non-optic pathway glioma was seen in 27 (17%) cases. Skeletal abnormalities were seen in 27 (17%) of cases. A first-degree relative with NF1 was seen in 83 (52%) of cases. Epilepsy was the presenting feature of 27 (17%) cases. Cognitive impairment was found in 15 (9.4%) patients. Genetic mutation was seen in 82/100 cases, the rest were negative. The types of mutations were as follows: nonsense 30 (36.6%); missense 20 (24.4%); splicing site mutation 12 (14.6%); frameshift 10 (12.2%); microdeletion 7 (8.5%); and whole gene deletion 3 (3.75%) patients. No phenotype-genotype correlation was seen. Conclusion In this cohort of Saudi pediatric patients with NF1, optic pathway glioma and other brain tumors were prevalent. The most common mutation is the nonsense mutation.