Neurofibromatosis Type 2

Neurofibromatosis Type 2 (NF2) is a rare, genetically inherited, progressive disease that affects the central nervous system. Characterized primarily by vestibular schwannomas originating from the auditory nerve, NF2 can lead to hearing loss, balance problems, facial paralysis, and various neurological symptoms over time. If you would like more comprehensive information about this disease, please take a look at our content. We wish you all good health and happy reading.

What is Neurofibromatosis Type 2 (NF2)?

Neurofibromatosis Type 2 (NF2) is a rare hereditary disease characterized by the development of benign tumors in the central and peripheral nervous systems. This disease arises from a mutation in the NF2 gene located on chromosome 22, causing the loss of function of a protein called merlin (schwannomin) that regulates cell growth. In this context, patients may experience progressive hearing loss, tinnitus, and balance disorders. Various tumor types, such as meningiomas, ependymomas, and facial nerve schwannomas, may also develop in NF2. Consequently, while there is no definitive cure for NF2, early diagnosis, regular follow-up, and multidisciplinary approaches involving surgery, radiosurgery, and supportive treatments can help control the disease and maintain quality of life.

How Common Is Schwannomatosis Associated with NF2 (Neurofibromatosis Type 2)?

Schwannomatosis associated with NF2 (Neurofibromatosis Type 2) is among the rare genetic diseases. Therefore, it is seen in approximately 1 in 25,000–40,000 people in the general population, which classifies NF2 as a rare disease. Furthermore, the disease occurs at similar rates in both women and men and usually begins to show clinical symptoms during childhood, adolescence, or young adulthood. Furthermore, while approximately half of the cases show familial inheritance, the other half develop as a result of sporadic genetic mutations without a family history. Although rare, this disease requires regular monitoring and follow-up at specialist centers due to its neurological effects and significant impact on quality of life.

What causes schwannomatosis associated with NF2 (neurofibromatosis type 2)?

It is responsible for the production of the tumor suppressor protein merlin (schwannomin), which regulates cell growth and cell-to-cell interactions. Mutations in the NF2 gene cause the merlin protein to lose its function, leading to the uncontrolled proliferation of Schwann cells and the development of schwannomas originating from nerve sheaths. Therefore, although the disease can be autosomal dominant, approximately half of the cases develop as a result of sporadic genetic mutations without a family history. Consequently, this genetic disorder paves the way for the formation of multiple tumors, particularly in the vestibular nerve, as well as in the cranial and spinal nerves, leading to the onset of schwannomatosis associated with NF2.

How is NF2 Diagnosed?

Neurofibromatosis Type 2 (NF2) is diagnosed through a comprehensive process that involves evaluating clinical findings along with imaging and genetic testing. In this diagnostic process, the patient's detailed medical history is first taken; in particular, hearing loss starting at an early age, balance disorders, symptoms related to facial nerve involvement, and family history are inquired about. Following the clinical evaluation, magnetic resonance imaging (MRI) of the brain and inner ear is the primary diagnostic tool, and the detection of bilateral vestibular schwannomas is considered a strong diagnostic criterion for NF2. When necessary, spinal cord MRI is used to investigate meningiomas, ependymomas, and other spinal tumors. Additionally, genetic testing can confirm the diagnosis by demonstrating a mutation in the NF2 gene and plays an important role, especially in familial cases and in patients suspected at an early age.

NF2 Tumor Types

• Vestibular Schwannomas (Acoustic Neuromas)

Vestibular schwannomas are the most characteristic tumors of NF2 and are usually found in both ears (bilateral). They originate from the vestibulocochlear nerve (8th cranial nerve), which is responsible for hearing and balance. Therefore, these tumors can cause progressive hearing loss, tinnitus, and balance disorders. Furthermore, NF2 often appears at a young age, and as the tumors grow, they can press on the brain stem over time, causing serious neurological problems.

• Facial Nerve Schwannomas

Facial nerve schwannomas affect the 7th cranial nerve, which controls the facial muscles. These effects can cause weakness, asymmetry, and facial paralysis in the facial muscles. Additionally, difficulty closing the eye, drooping at the corner of the mouth, and loss of facial expression during speech may be observed. Thus, facial nerve schwannomas may coexist with vestibular schwannomas, and preserving facial nerve function is of great importance during treatment planning.

• Other Cranial Nerve Schwannomas

NF2 can also affect cranial nerves other than the vestibular and facial nerves. The trigeminal (5th nerve), oculomotor (3rd nerve), and lower cranial nerves are particularly susceptible. These involvement may manifest with various neurological symptoms such as numbness in the facial region, pain, difficulty chewing, limited eye movement, swallowing and speech disorders. Therefore, simultaneous involvement of multiple cranial nerves is a typical finding in NF2.

• Meningiomas

Meningiomas are benign tumors originating from the meninges surrounding the brain and spinal cord and are common in NF2 patients. These tumors, which can be single or multiple, can grow over time and exert pressure on brain tissue. As a result, headaches, epileptic seizures, visual disturbances, and focal neurological deficits may occur.

• Ependymomas

Ependymomas develop from ependymal cells that line the spinal canal and brain ventricles. This condition is particularly common in spinal cord-located ependymomas. For this reason, it can lead to symptoms such as weakness in the arms and legs, sensory loss, gait disturbance, and problems with bladder and bowel function. Additionally, despite their slow growth, they can cause significant functional impairments due to spinal cord compression.

• Spinal Schwannomas

The final tumor type, spinal schwannomas, originate from the peripheral nerve roots emerging from the spinal cord and are commonly seen in NF2 patients. Therefore, they cause symptoms such as back or waist pain, numbness in the arms and legs, tingling, and muscle weakness. Additionally, the presence of multiple spinal schwannomas together is one of the distinguishing features of NF2, and they require regular spinal imaging for monitoring.

What are the symptoms of NF2-related schwannomatosis (neurofibromatosis type 2)?

Neurofibromatosis type 2 has certain main symptoms. These symptoms vary from person to person and do not occur with the same severity in everyone. In this context, the symptoms of neurofibromatosis type 2 are as follows:

• Hearing loss
• Tinnitus
• Balance disorder and dizziness
• Weakness in facial muscles
• Facial paralysis
• Difficulty closing the eyes
• Headache
• Vision problems
• Numbness in arms and legs
• Muscle weakness
• Gait disorder
• Difficulty speaking and swallowing
• Back and waist pain
• Psychological effects

How is Schwannomatosis Associated with NF2 (Neurofibromatosis Type 2) Treated?

Various treatment methods are used in the treatment of neurofibromatosis type 2. These treatment methods vary depending on the course of the disease. In this context, the treatment methods used are as follows:

Gracilis Muscle Transfer

Facial paralysis in NF2 usually occurs as a result of permanent damage to the facial nerve following vestibular schwannomas or surgery for these tumors. In this case, gracilis muscle transfer is an effective surgical method used to restore facial expressions. In this surgical method, the gracilis muscle taken from the thigh is transferred to the facial region and, due to its reliability in most NF2 patients, is connected to the masseter nerve. The goal is to enable active smiling and facial expression. It is particularly preferred in cases of long-term and irreversible facial paralysis.

Free Functional Muscle Flap

The free functional muscle flap is one of the basic surgical approaches aimed at restoring functional movement in permanent facial paralysis associated with NF2. This approach typically involves the gracilis muscle, which is the most commonly used muscle, and the basic principle is to transfer the muscle, along with its blood vessels and nerves, to the facial region using microsurgical techniques. Furthermore, due to progressive nerve involvement in NF2, the free functional muscle flap, when combined with a strong nerve graft, contributes to restoring facial symmetry and mimic function.

Temporalis Muscle Flap

The temporalis muscle flap is an alternative facial reanimation method for NF2 patients who are not suitable for free muscle transfer or who require additional support. This temporalis muscle flap involves directing the temporalis muscle, one of the masticatory muscles, toward the corner of the mouth to create facial movement. While this offers the advantage of achieving results in a shorter time, the resulting facial expressions may be more limited and less natural compared to free muscle transfer.

Gold Eyelid Weight

Infacial paralysis associated with NF2, which is commonly seen in cases of insufficient eyelid closure, poses a serious risk to corneal health. In such cases, a gold eyelid weight is placed on the upper eyelid to assist in the passive closure of the eye. Thus, the gold eyelid weight generally presents itself as a protective treatment option.

Eyelid Reconstruction Surgery

Eyelid reconstruction surgery is performed to correct eyelid laxity, asymmetry, and closure disorders that develop in facial paralysis associated with NF2. This procedure is planned to protect the eye and maintain visual function. It can also be performed in conjunction with methods such as gold eyelid weights.

Facial Sling Surgery

Facial sling surgery is a method aimed at providing static support in NF2-related facial paralysis. The goal is to lift the facial tissues that sag downward due to gravity using suspension materials and to improve facial symmetry. In this context, it provides significant relief to the patient in terms of speech, eating, and aesthetic appearance and is performed in addition to functional surgeries.

Differences Between Neurofibromatosis Type 2 and Type 1

• NF1 develops due to mutations in the NF1 gene located on chromosome 17, while NF2 arises as a result of mutations in the NF2 gene found on chromosome 22.
• NF1 is more common in the population (approximately 1/3,000), while NF2 is a rarer disease (approximately 1/25,000–40,000).
• NF1 usually manifests in childhood, while NF2 mostly appears during adolescence or young adulthood.
• Subcutaneous neurofibromas and plexiform neurofibromas are common in NF1, while bilateral vestibular schwannomas are the most typical tumors in NF2.
• Hearing and balance problems are rare in NF1, while hearing loss, tinnitus, and balance disorders are common findings in NF2.
• Facial nerve involvement is rare in NF1, whereas facial nerve involvement and facial paralysis are more common in NF2.
• Café-au-lait spots and axillary or inguinal freckling are common in NF1, whereas skin findings are generally milder and more limited in NF2.
• Lisch nodules on the iris are typical in NF1, whereas cataracts developing at an early age are more frequently observed in NF2.
• Optic gliomas and some brain tumors may be seen in NF1, whereas meningiomas, ependymomas, and multiple cranial and spinal tumors are common in NF2.
• While facial reanimation surgery is generally not required in NF1, it is more frequently considered in patients with facial paralysis in NF2.
• The clinical course of NF1 is more variable and often slower progressive, while NF2 has a more progressive course and requires close follow-up.
• While treatment for NF1 focuses more on symptoms and complications, a multidisciplinary approach, surgery, radiosurgery, and rehabilitation practices are at the forefront for NF2.

Long-Term Facial Paralysis Associated with NF2

Long-Term Facial Paralysis Associated with NF2 is a complex and difficult-to-manage clinical condition that arises due to permanent damage to the facial nerve as a result of tumors or surgical interventions targeting these tumors, due to the progressive nature of Neurofibromatosis Type 2. In this condition, vestibular schwannomas and facial nerve schwannomas, in particular, disrupt the structural integrity of the nerve, leading to gradual denervation of the facial muscles. This manifests as functional problems such as loss of facial expression, facial asymmetry, difficulty speaking and eating, and inadequate eye closure. On the other hand, in long-term facial paralysis, the spontaneous healing potential of the facial nerve is largely eliminated due to the development of atrophy and fibrosis in the facial muscles, and conservative treatments are insufficient. Therefore, the treatment approach mostly focuses on facial reanimation surgeries, especially free functional muscle transfers and static supportive interventions. Consequently, while protective measures for the eyes, rehabilitation programs, and multidisciplinary follow-up are crucial in the early stages, the long-term goal is not only to improve aesthetic appearance but also to preserve the patient's daily living functions—such as speech, nutrition, eye health, and social interaction—at the highest possible level.

Facial Reanimation Surgery in NF2 Patients

Facial reanimation surgery in NF2 patients involves advanced surgical approaches aimed at restoring facial expressions and functional symmetry in cases of permanent facial paralysis associated with neurofibromatosis type 2. Particularly in NF2, facial paralysis most often arises from irreversible damage to the facial nerve following vestibular schwannomas or surgical interventions targeting these tumors; therefore, the nerve's potential for spontaneous recovery is limited in treatment planning. Therefore, the most commonly preferred methods in facial reanimation surgery include free functional muscle transfers, particularly gracilis muscle transfer and its innervation with the masseter nerve. In addition to surgery, complementary methods such as gold eyelid weights and eyelid reconstructions for inadequate eyelid closure, static suspension procedures to improve facial symmetry, and temporalis muscle flaps in selected cases may also be applied.

All these interventions are planned individually by multidisciplinary teams, taking into account the patient's age, duration of facial paralysis, tumor burden, and general neurological status. The goal is not only aesthetic improvement but also the permanent improvement of daily life functions such as speech, feeding, eye health, and social interaction.

Living with Neurofibromatosis Type 2 and Facial Paralysis

Living with Neurofibromatosis Type 2 and facial paralysis requires a multifaceted adaptation process, both physically and psychosocially, due to the chronic and progressive nature of the disease. Facial paralysis associated with NF2 can lead to functional problems that directly affect daily life, such as loss of facial expressions, difficulties with speech and eating, problems closing the eyes, and facial asymmetry. This condition is not limited to aesthetic concerns; it can also have significant effects on social interaction, self-confidence, and emotional well-being. However, it is possible to maintain quality of life through early diagnosis, regular neurological and radiological follow-up, facial reanimation surgeries, eye-preserving interventions, and physical therapy and rehabilitation applications.

On the other hand, thanks to personalized treatment and support programs planned by multidisciplinary teams, individuals living with NF2 and facial paralysis can increase their functional independence, participate more actively in social life, and establish a long-term balance with the disease.