From the Guidelines
Neurofibromatosis (NF) is a genetic disorder that causes tumors to form on nerve tissue, with two main types: NF1 and NF2, which are characterized by distinct clinical features and caused by mutations in specific genes on chromosomes 17 and 22, respectively. The diagnosis of NF2 is primarily based on the presence of bilateral vestibular schwannomas (VS) or a unilateral VS with at least two other NF2-related tumors 1. NF1 typically presents with café-au-lait spots, freckling, and benign neurofibromas, while NF2 primarily causes VS that affect hearing and balance.
Clinical Features and Management
The clinical management of NF2 involves regular monitoring by a multidisciplinary team, including neurologists, dermatologists, ophthalmologists, and geneticists. Treatment is symptom-based, focusing on surgical removal of problematic tumors, pain management, and addressing complications like high blood pressure, scoliosis, or learning disabilities in children 1. Surgery is the primary clinical tool for NF2 management, although it can lead to significant morbidity, including deafness, loss of facial nerve function, infections, and headaches.
Genetic Basis and Inheritance
Both NF1 and NF2 are autosomal dominant disorders, with a 50% chance of passing the condition to offspring 1. Genetic counseling is recommended for affected individuals planning families. While there's no cure for NF, the FDA approved selumetinib (Koselugo) for children with NF1 who have symptomatic, inoperable plexiform neurofibromas. Regular screening is essential as patients have an increased risk of certain malignancies.
Key Considerations
- NF2 mutations are found in >92% of NF2 individuals in the second or greater generation of families 1.
- Population studies suggest that up to 1:300 people will develop a tumor with an underlying sporadic NF2 mutation in their lifetime 1.
- VS in NF2 patients are known to grow faster than their sporadic counterparts, highlighting the need for effective treatments and alternative or adjunct therapies to surgery 1.
From the Research
Definition and Types of Neurofibromatosis
- Neurofibromatosis (NF) is an autosomal genetic disorder with three types, including NF1, NF2, and schwannomatosis 2, 3, 4.
- NF1 is the most common neurogenetic disorder, with a birth incidence of 1 in 3000 4.
- The hallmark lesion of NF1 is the neurofibroma, a benign tumor derived from the nerve sheath and composed of a mixture of proliferating Schwann cells, fibroblasts, mast cells, and pericytes 4.
Clinical Manifestations and Complications
- NF1 is characterized by bulging and deforming masses arising from multiple nerves involving skin folds and connective tissues 3.
- Café au lait macules are typically the initial clinical manifestation of NF1 and tend to increase in size and number throughout childhood and puberty 4.
- Other findings include gliomas, learning disability, vasculopathy, and bony abnormalities 4.
- NF1 patients develop multiple tumors (neurofibromas); approximately 8%-15% percent of them present with malignant peripheral nerve sheath tumors (MPNST) within the patient's lifetime 3.
- Tumor ulceration is a rare but possible complication of NF1 3.
Diagnosis and Management
- The diagnosis of NF1 is based on clinical criteria, including the presence of multiple café au lait macules, neurofibromas, and other characteristic features 5.
- Current treatment of patients with NF1 remains primarily surgical, with genetic counseling essential for adult patients because molecular diagnostic testing can minimize the risk of transmission to children 4, 6.
- A multidisciplinary management approach is ideal, with treatment options including surgery, radiotherapy, and targeted biological agents 3, 6.
- Further prospective studies are needed to confirm the efficacy, safety, and cost/benefit ratio of new therapeutic approaches and the optimal timing for their use in patients with NF1 6.