What is neurofibromatosis?

Types of neurofibromatosis Types of neurofibromatosis include three main forms: 1. NF1: It is the most common type and is usually associated with brown spots on the skin, subcutaneous nodules and learning problems. 2. NF2: It is rarer and mostly causes auditory tumors such as eighth nerve schwannomas 3. Schwannomatosis: It is a rare form of this disease, which is characterized by chronic pain caused by multiple schwannomas in the peripheral nerves. The difference between **NF**1 and **NF2** is mostly in clinical symptoms, age of onset and genes involved. Accurate identification of the type of disease helps in early diagnosis and better management. ### comparison table of types of neurofibromatosis Symptoms of neurofibromatosis Symptoms of neurofibromatosis vary depending on the type of disease, but some symptoms can be warning signs. In type NF1, light brown spots on the skin (called café au lait), subcutaneous nerve nodules, and learning difficulties are common. While the symptoms of neurofibromatosis type 2 mostly include hearing loss, tinnitus, imbalance and sometimes blurred vision, which are caused by tumors on the auditory and optic nerves. Also, in some patients with brain tumor symptoms, such as schwannoma or meningioma, it may also occur, which causes headache, dizziness or visual disturbances. ### Skin and appearance symptoms Neurofibromatosis often presents with skin symptoms and benign tumors under the skin, which can be an early sign of the disease. These symptoms include the following: - Light brown spots (café oleh) that appear since childhood and more than 6 with a diameter of more than 5 mm can indicate NF1. - Neurofibromas, soft and benign tumors on or under the skin, which may cause disfigurement or psychological distress and require medical follow-up. ### Neurological and cognitive complications Neurofibromatosis can have profound effects on the nervous system and cognitive abilities. Neurological and cognitive complications include the growth of nerve tumors in the brain or spine, which sometimes cause persistent headaches, seizures, or muscle weakness. In NF2, hearing loss is an important symptom, usually caused by tumors on the auditory nerve. In NF1, many patients have learning difficulties, attention disorders, and delayed cognitive development. These problems can affect a person's academic or social performance and require appropriate psychological evaluations and academic support. ### Neurological and cognitive complications Neurological and cognitive complications in neurofibromatosis can seriously affect a person's quality of life. In NF1, the growth of brain or spinal cord tumors may cause headaches, seizures, or limb weakness. Many children with NF1 have learning difficulties, attention deficit disorder, and cognitive disabilities. On the other hand, hearing loss is one of the most obvious symptoms of neurofibromatosis type 2, which is caused by tumor growth on the auditory nerve and may be accompanied by tinnitus or imbalance. Early identification of these problems through medical and psychological evaluations is crucial to prevent the development of complications. Causes of neurofibromatosis; The role of genetics in this disease Neurofibromatosis is a genetic disorder that occurs as a result of specific mutations in genes responsible for controlling cell growth. In most cases, this disease is inherited from parents to children, but it may also be seen in some patients without a family history. The genes involved in this disease play a key role in regulating cell division, and their dysfunction causes the growth of **benign brain tumor types** and non-cancerous tumors. The main genetic factors include the following: - Mutation in **NF**1 gene (chromosome 17): the main cause of neurofibromatosis type 1, which causes the uncontrolled growth of neurofibromas. - Mutation in **NF**2 gene (chromosome 22): causes neurofibromatosis type 2 and growth of hearing tumors (schwannoma). - Mutations in **SMARCB**1 or **LZTR1:** the cause of schwannomatosis, which is associated with the painful development of peripheral schwannomas. - Autosomal dominant inheritance: if one of the parents has a defective gene, the child has a 50% chance of contracting the disease. - New mutations (sporadic): In about half of NF1 and NF2 cases, the disease is caused by a new mutation and there is no history in the family. Accurately knowing the causes of neurofibromatosis and understanding the role of genetics in it is important for genetic counseling, family decisions and proper management of the disease. Families with a history of neurofibromatosis should consult a geneticist to determine the possibility of transmission to the next generation. diagnosis of neurofibromatosis; From examination to genetic testing Diagnosis of neurofibromatosis is a detailed and multi-step process that requires the specialized knowledge of a neurologist. According to the National Institutes of Health (NIH) diagnostic protocols, the first step is a physical examination to check for skin lesions, neurofibromas, or hearing disorders. In case of clinical doubt, imaging such as MRI or CT is used to identify nerve tumors. Along with these methods, genetic testing plays an important role in definitive diagnosis; Especially to differentiate between NF1, NF2 and schwannomatosis. Clinical experience shows that early diagnosis through these steps can be very effective in controlling symptoms and reducing long-term complications. ### Clinical examination The first step in diagnosing neurofibromatosis is a clinical examination by a neurologist or dermatologist. At this stage, the doctor looks for physical signs such as café au lait spots, cutaneous neurofibromas, and bone or nerve abnormalities. National Institutes of Health (NIH) clinical criteria for the diagnosis of NF1 include the presence of at least six skin lesions, two neurofibromas, or Leish eye nodules. In suspicious cases, checking family history is also very important. A careful examination can clarify the possibility of the disease without the immediate need for expensive tests and, if necessary, suggest additional steps such as imaging or genetics. ### Imaging role Medical imaging, especially MRI, is a key tool in identifying neurofibromatosis-related nerve tumors. MRI can show auditory (in NF2), spinal cord or brain tumors with high accuracy, even when clinical symptoms have not yet appeared. In cases where hearing loss or balance is present, an MRI of the inner ear and brainstem is recommended. Also, it is used in NF1 to investigate optic tumors or brain lesions. CT scan is used in special cases such as bone conflicts. Imaging plays an important role in confirming clinical findings and guiding treatment. ### Genetic testing Genetic testing plays an important role in confirming the diagnosis of neurofibromatosis, especially in cases where the clinical symptoms are not clear or when the differential diagnosis between NF1, NF2, and schwannomatosis requires more precision. This test detects mutations related to NF1, NF2 or SMARCB1 and LZTR1 genes by examining a person's DNA. A positive result can provide accurate information about prognosis, the risk of transmitting the disease to children, and treatment planning. In families with a history of the disease, genetic testing before birth or before pregnancy is also possible. The results should be interpreted by a geneticist. Treatment of neurofibromatosis Treatment of neurofibromatosis depends on the type of disease, severity of symptoms and individual conditions, and its approach is often a combination of medical and supportive treatments. In some cases, surgery is performed to remove painful or troublesome tumors. Drugs such as MEK inhibitors have been shown to be effective in reducing the size of neurofibromas, particularly in the management of NF1. Physiotherapy, speech therapy and psychological counseling are also necessary to improve the quality of life. In some patients, regular use of imaging and hearing or vision monitoring is part of ongoing care. The main focus of treatment is on controlling symptoms, preventing the progression of complications and providing personalized treatments for each patient. ### Surgery and invasive interventions Surgery is one of the main methods for treating tumors associated with neurofibromatosis, especially neurofibromas and schwannomas. When tumors cause pain, nerve dysfunction, or cosmetic problems, your doctor may recommend removing them. In cases where the tumors are located in sensitive areas such as the brain or spine, surgery must be performed with high precision and by a specialist team. The goal of surgery is to reduce nerve pressure and improve the patient's function, but there is also a risk of damage to nerve tissues. The choice of surgery should be made with careful consideration of the advantages and disadvantages and within the framework of a comprehensive treatment plan. ### Drug therapy and supportive care In recent years, there have been advances in drug therapy for neurofibromatosis, especially NF1. MEK inhibitor drugs such as selumetinib have been able to reduce the growth of complex neurofibromas in some patients. This treatment is often accompanied by regular monitoring and checking for side effects. Supportive care also plays an important role in disease management; Includes: - Physiotherapy - Speech therapy - Psychotherapy - Educational support for children These interventions help to improve the quality of life, increase independence and reduce the psychological pressure of patients and their families. The treatment approach should be designed based on the specific needs of each person. ### Stereotactic radiosurgery Stereotactic radiosurgery is an advanced, non-invasive treatment method that uses focused radiation to destroy small tumors, especially schwannoma of the auditory nerve in NF2. Unlike open surgery, this method does not require incision or general anesthesia and the patient is usually discharged on the same day. This technique targets tumor cells with high precision, while largely sparing the surrounding healthy tissue. Radiosurgery is a suitable option for patients who are unable to undergo surgery for medical reasons or whose tumors are located in sensitive areas. ### Brain stem and cochlear hearing implant In patients with **neurofibromatosis type 2** who have severe hearing loss or complete deafness, brainstem auditory implant or cochlear implant can help to partially restore hearing. In cases where the auditory nerve is completely destroyed, a brainstem implant is a better alternative and sends sound signals directly to the brainstem. If the nerve still retains part of its function, cochlear implantation is a more suitable option. These methods require expert examination by an ear and neurosurgeon, and after that, hearing rehabilitation sessions are performed. ### Traditional medicine Although some patients seek complementary solutions such as traditional medicine, neurofibromatosis is a complex genetic disease related to vital nerve structures. The use of non-specialist methods such as herbal therapy or local massages can cause a delay in correct treatment or exacerbation of symptoms. For this reason, experts strongly recommend to avoid non-scientific interventions in this field. Visiting a neurologist or a geneticist, and following scientific and approved methods, is necessary to properly manage the disease and prevent irreversible complications. Prevention of neurofibromatosis Prevention of neurofibromatosis is challenging due to the genetic nature of this disease. In many cases, the disease is passed from parent to child, and sometimes it occurs due to a new mutation in the gene. Although it cannot be completely prevented, using scientific methods and expert advice can increase the probability of transmission or early diagnosis. Prevention and risk reduction measures include: - **Pre-pregnancy genetic counseling:** For couples who have a family history of the disease, it is important to check the risk of transmission to the next generation. - **Prenatal diagnosis (PND):** By sampling the amniotic fluid or placental villi, it is possible to check the defective genes in the fetus. - **Pre-implantation diagnosis (PGD):** In laboratory fertilization, it is possible to examine the embryos genetically before transferring them to the uterus. - **Genetic screening tests for families at risk:** Identification of potential disease carriers in close relatives. - **Awareness and training:** Increasing families' awareness of early symptoms and the importance of visiting a specialist doctor.