Case Report for Two Siblings Carrying Neurofibromatosis Type 1 with a Rare NF1: c.5392C>T Mutation

Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome caused by mutations on the NF1 gene, which is located at chromosome 17q11.2. Although an autosomal dominant inheritance pattern is well-established, about half of new cases are the result of de novo NF1 mutations. Neurofibromatosis type 1 has an incidence rate of 1/2600–3000 individuals, making it a major public health problem. The product of the NF1 gene, the neurofibromin protein, is known to play a critical role in cellular differentiation and in tumor suppression. Due to widespread expression of neurofibromin in numerous tissues, particularly in cutaneous and nervous systems, NF1 mutations cause a wide variety of clinical symptoms, including cutaneous and ocular lesions such as café au lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, choroidal freckling and internal tumors. In this article, we report the cases of two siblings with NF1, a 21-year-old male and his 24-year-old sister, who have the same c.5392C>T mutation on the NF1 gene (p.Gln1798 Ter). Café au lait macules and freckling were the prominent clinical features in both siblings. However, a plexiform neurofibroma was also observed on the left arm of the sister, which is known to carry potential risk for malignant transformation. Although the mutation was previously described once, to the best of our knowledge, no case report has been published since then.