Neurofibromatosis Type 2

Neurofibromatosis type 2 is a neurocutaneous disorder that can arise from mutations in the NF2 gene located in chromosome 22 and may be inherited in an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance fashion or occur from de novo mutations. The main clinical features are bilateral vestibular schwannomas, intracranial/spinal meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma, and intramedullary and extramedullary spinal tumors. Other features can include eye lesions such as cataracts, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions, and peripheral neuropathy. Diagnosis is made clinically from history and examination and confirmed with MRI, molecular testing, and histopathology. Tumor surveillance and follow-up with screening of at-risk family members is recommended. Management includes surgical interventions, radiation therapy, and/or monoclonal antibody therapy with bevacizumab.

Last update:

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Overview

Epidemiology

  • The incidence of neurofibromatosis type 2 (NF2) is 1 in 25,000.
  • Bilateral vestibular schwannomas are present in 90%–95% of affected individuals.
  • Meningiomas are present in 50% of affected individuals.
  • De novo mutations that occur in the absence of a positive family history are present in > 50% of affected individuals.
  • NF2 gene mutations are detected in > 93% of families, with multiple members affected with NF2.

Etiology

  • Caused by NF2 gene mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations located in chromosome 22
  • The abnormal gene:
    • May be passed down from 1 parent ( autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance)
    • May occur via de novo mutations 
  • Risk of gene transmission from parent to offspring is 50%.

Pathogenesis

  • Mutations occur in NF2 gene, located on chromosome 22.
  • NF2 gene codes for merlin (schwannomin):
    • Cell-membrane–related protein 
    • Acts as a tumor suppressor 
    • Found on Schwann cells
  • Mutations lead to loss of merlin expression, allowing tumor eruption in the central and peripheral nervous systems.
  • 2-hit hypothesis:
    • Schwannomas and other tumors occur only after inactivation of both NF2 alleles:
      • Affected individuals are born with 1 abnormal allele.
      • Abnormalities of the 2nd allele are acquired.
    • Acquired loss of function in the entire NF2 gene or in chromosome 22 is most common.
    • Point mutations of the wild-type allele occur less commonly.

Clinical Presentation

The clinical presentation of NF2 may vary widely between individuals with de novo mutations and families carrying genetic mutations. Younger ages at onset are often associated with an atypical presentation with more severe symptoms.

Clinical manifestations of nf2

Clinical manifestations of NF2

Image by Lecturio.

Age at onset

  • Childhood onset:
    • Visual/ocular manifestations
    • Pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Weakness
    • Mononeuropathy Mononeuropathy Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathies affect a single nerve. Mononeuropathy and Plexopathy
    • Cutaneous tumors
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Adult onset (most commonly at about age 20):
    • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Tinnitus

Neurologic lesions

  • Vestibular schwannomas (cranial nerve (CN) VIII):
    • Present in approximately 95% of NF2-affected individuals
    • Develop by 30 years of age
    • Typically bilateral
    • Typically benign
    • Symptoms:
      • Tinnitus
      • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
      • Loss of balance/equilibrium
  • Schwannomas of other cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. Overview of the Cranial Nerves:
    • Present in 25%–50% of NF2-affected individuals
    • Not observed in CN I or CN II (absence of Schwann cells)
    • Cause compressive cranial nerve palsies
    • Most commonly observed in:
      • CN III (oculomotor)
      • CN V (trigeminal)
      • CN VII (facial)
  • Intracranial meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma:
    • Present in 45%–60% of NF2-affected individuals
    • Often multiple
    • Develops in NF2 at a younger age than in sporadic cases
    • Symptoms depend on location and size:
      • Focal neurologic deficits
      • CSF flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure obstruction
      • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Spinal meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma:
    • Present in approximately 20% of NF2-affected individuals
    • Arise from extramedullary space
    • Symptoms depend on location and size:
      • Back pain Back pain Back pain is a common complaint among the general population and is mostly self-limiting. Back pain can be classified as acute, subacute, or chronic depending on the duration of symptoms. The wide variety of potential etiologies include degenerative, mechanical, malignant, infectious, rheumatologic, and extraspinal causes. Back Pain
      • Nerve root pain/paresthesia
      • Muscle weakness/paralysis
      • CSF flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure obstruction
  • Spinal ependymomas:
    • Present in 20%–50% of NF2-affected individuals
    • Typically arise from intramedullary space
    • Symptoms depend on location and size:
      • Back pain Back pain Back pain is a common complaint among the general population and is mostly self-limiting. Back pain can be classified as acute, subacute, or chronic depending on the duration of symptoms. The wide variety of potential etiologies include degenerative, mechanical, malignant, infectious, rheumatologic, and extraspinal causes. Back Pain
      • Nerve root pain/paresthesia
      • Muscle weakness/paralysis
      • CSF flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure obstruction
  • Peripheral neuropathy:
    • Present in > 65% of NF2-affected individuals
    • May present as a compression neuropathy (mononeuropathy)
    • May present as a mononeuropathy multiplex
    • May present as a systemic (nonfocal) sensorimotor neuropathy
    • Symptoms of mononeuropathy dependent on the affected nerve(s).
    • Symptoms of systemic polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy:
      • Neuropathic pain/ paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Respiratory Alkalosis/sensory loss in a glove-and-stocking distribution
      • Loss of strength, coordination, dexterity in a glove-and-stocking distribution 

Eye lesions

  • Cataracts:
    • Present in 60%–80% of NF2-affected individuals
    • Present with visual loss, lens opacity
  • Epiretinal membranes:
    • Present in approximately 80% of NF2-affected individuals
    • White/gray membranes with distinct white edges
    • May be translucent or semitranslucent
    • Do not typically interfere with vision
  • Retinal hamartomas:
    • Present in 5%–20% of NF2-affected individuals
    • Affect the macula 
    • Present with visual loss

Skin lesions

  • May occur anywhere, no particular area of predilection 
  • Most commonly skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin tumours are schwannomas, though neurofibromas or mixed histology may be observed.
  • Skin plaques:
    • Present in 40%–50% of NF2-affected individuals
    • Circumscribed, slightly raised, slightly hyperpigmented, scaly, rough lesions
    • Typically < 2 cm in diameter
  • Subcutaneous tumors:
    • Present in 40%–50% of NF2-affected individuals
    • Develop as swellings along peripheral nerves
    • May be palpated as fusiform or nodular swellings 
    • Tenderness to palpation may be noted.
  • Intradermal tumors:
    • Present in 60%–70% of NF2-affected individuals
    • Well-demarcated, superficial lesions with blue/purple coloration
    • Soft to palpation

Diagnosis

Clinical criteria for neurofibromatosis type 2 (revised Manchester criteria)

  • Any 1 of the following:
    • Bilateral vestibular schwannoma Vestibular schwannoma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma at < 70 years of age
    • Unilateral vestibular schwannoma Vestibular schwannoma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma at < 70 years and 1st-degree relative (not a sibling alone) with NF2
  • Any 2 of the following:
    • Meningioma, nonvestibular schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma, ependymoma Ependymoma Ependymomas are glial cell tumors arising from CSF-producing ependymal cells lining the ventricular system. Ependymomas most commonly occur within the posterior fossa in contact with the 4th ventricle, or within the intramedullary spinal cord. Ependymoma, cataract; and 
    • 1st-degree relative with NF2 or unilateral vestibular schwannoma Vestibular schwannoma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma and negative LZTR1 testing (if ≥ 2 non-intradermal schwannomas)
  • Other criteria:
    • Multiple meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma and:
      • Unilateral vestibular schwannoma Vestibular schwannoma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma or
      • Any 2 of the following: nonvestibular schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma, ependymoma Ependymoma Ependymomas are glial cell tumors arising from CSF-producing ependymal cells lining the ventricular system. Ependymomas most commonly occur within the posterior fossa in contact with the 4th ventricle, or within the intramedullary spinal cord. Ependymoma, cataract
    • Constitutional or mosaic pathogenic NF2 gene mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations from the blood or by the identification of an identical mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations from 2 separate tumors in the same individual 

Clinical diagnosis

  • Detailed clinical and family history
  • Physical examination:
    • Auditory evaluation
    • Ophthalmic evaluation
    • Neurologic examination
    • Skin examination

Molecular testing

  • Indications:
    • 1st-degree relative with NF2 
    • Presence of multiple spinal tumors 
    • Presence of cutaneous schwannomas
    • Presence of vestibular schwannoma Vestibular schwannoma Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Acoustic Neuroma at < 30 years of age
    • Presence of meningioma Meningioma Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Meningioma or schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma (nonvestibular) at < 25 years of age
  • Begin with analysis of tumor DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure with sequencing for NF2 abnormalities, followed by analysis of blood lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes for the same NF2 abnormality.
Vestibular schwannoma histopathology

Vestibular schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma histopathology

Image: “Vestibular schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma” by Pećina-Slaus N, Zeljko M, Pećina HI, Nikuseva Martić T, Bacić N, Tomas D, Hrasćan R. License: CC BY 2.5

Imaging

  • MRI with contrast is the method of choice.
  • Scans of the brain and entire spine are recommended to evaluate for intracranial/spinal tumors.

Management

Management of NF2 is multidisciplinary and often involves contributions from multiple specialists.

  • Consultations with the following specialties:
    • Oncology
    • Neurology
    • Neuroradiology
    • Ophthalmology
    • Dermatology
    • Audiology
    • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics/genetic counseling
    • Neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery/ skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull-base surgery 
  • Tumor surveillance and follow-up:
    • Annual history and physical exam (audiology, ophthalmic evaluation, neurologic, and cutaneous examination)
    • Brain MRI every 12 months beginning at 10 years of age
    • Spinal MRI every 24–36 months beginning at 10 years of age
  • Vestibular schwannoma Schwannoma Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Schwannoma(s): 
    • Surgery:
      • Neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery or skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull-base surgery consultation
      • Surgery may be complex and high risk depending on size, location, and multifocality.
    • Bevacizumab: 
      • Monoclonal antibody against vascular endothelial growth factor
      • Induces tumor shrinkage and hearing improvement
    • Other targeted therapies:
      • Everolimus: chemotherapeutic kinase inhibitor that decreases tumor blood supply.
      • Lapatinib: chemotherapeutic tyrosine kinase inhibitor interrupts epidermal growth factor receptor (EGFR) pathways.
    • Hearing impairment: 
      • Cochlear implants
      • Brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem implants 
  • Meningioma: 
    • Surgery: 
      • Rapidly growing tumors
      • Tumors threatening functional loss
    • Radiation therapy:
      • Tumors that are surgically inaccessible or for which only partial resection is possible
      • Concern for development of secondary neoplasms
    • Targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted Therapy and Other Nontraditional Antineoplastic Agents with lapatinib is being investigated.
  • Intramedullary spinal tumors: 
    • Usually grow very slowly, with no symptoms for a long period
    • MRI surveillance is usually adequate.
    • Bevacizumab is 1st-line therapy.
    • Surgery is recommended if symptoms require intervention.
  • Genetic evaluation:
    • Identification of specific NF2 gene mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations
    • Screening of at-risk family members

Differential Diagnosis

  • Sporadic vestibular schwannomas: also known as acoustic neuromas. In the general population, sporadic vestibular schwannomas are relatively common. In contrast to NF2, sporadic vestibular schwannomas are typically unilateral and present at > 30 years of age. Presentation is with hearing loss and equilibrium problems. These lesions are diagnosed on clinical suspicion and confirmed with neuroimaging. Conservative and surgical options are similar to those outlined for NF2. 
  • Schwannomatosis: rare sporadic or familial form of neurofibromatosis associated with mutations in the SMARCB1 and LZTR1 genes located on chromosome 22. Schwannomatosis is characterized by multiple noncutaneous peripheral and intracranial schwannomas in the absence of bilateral vestibular schwannomas. Diagnosis is made with clinical evaluation and confirmed with biopsy. Management is symptomatic, treating the chronic pain that occurs in roughly half of all patients with schwannomatosis. 
  • Neurofibromatosis type 1 Neurofibromatosis type 1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder caused by mutations in the NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1 gene located in chromosome 17q11.2. Clinical manifestations can overlap with NF2, but the key differences include that Lisch nodules are seen in few numbers in NF2, schwannomas rarely undergo malignant transformation to a neurofibrosarcoma, the “dumbbell” spinal root tumors that are seen in both NF2 and NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1 are schwannomas in NF2 and neurofibromas in NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1, and NF2 is not associated with the cognitive impairment seen in NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1. Management is based on the clinical features and may vary from surgical removal to chemotherapy/radiotherapy for tumors, occupational and physical therapy for motor impairments, and treatment with growth hormone and bracing in bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones abnormalities. 
  • Tuberous sclerosis Tuberous sclerosis Tuberous sclerosis or tuberous sclerosis complex (TSC) is an autosomal dominant disorder with mainly neurocutaneous symptoms. Mutation in the TSC genes causes excessive tumor-like growths in the brain, eyes, heart, kidney, and lungs. Cutaneous manifestations include hypopigmentation (i.e., ash leaf spots, confetti lesions) or excessive growth (i.e., angiofibroma, shagreen patch). Tuberous Sclerosis: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder with mainly neurocutaneous symptoms. Mutation in the TSC genes causes excessive tumor-like growths in the brain, eyes, heart, kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys, and lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs. Cutaneous manifestations include hypopigmentation (i.e., ash-leaf spots, confetti lesions) or excessive growth (i.e., angiofibroma, shagreen patch). The diagnosis is made on clinical suspicion and confirmed by genetic testing. Management entails a multidisciplinary approach that targets monitoring and treatment of the various manifestations of the disorder.

References

  1. Evans, D.G. (2021). Neurofibromatosis type 2. UpToDate. Retrieved August 30, 2021, from https://www.uptodate.com/contents/neurofibromatosis-type-2
  2. Park, J.K. et al. (2020). Vestibular schwannoma (acoustic neuroma). UpToDate. Retrieved August 30, 2021, from https://www.uptodate.com/contents/vestibular-schwannoma-acoustic-neuroma
  3. Victorio, M.C. (2021). Neurofibromatosis. MSD Manual Professional Version. Retrieved August 28, 2021, from https://www.msdmanuals.com/professional/pediatrics/neurocutaneous-syndromes/neurofibromatosis
  4. Hsieh, D.T. (2018). Neurofibromatosis type 2. Medscape. Retrieved August 28, 2021, from https://emedicine.medscape.com/article/1178283
  5. Tiwari, R., Singh, A.K. (2021). Neurofibromatosis Type 2. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK470350/
  6. Asthagiri, A.R., et al. (2009). Neurofibromatosis type 2. Lancet 373:1974–1986. https://doi.org/10.1016/S0140-6736(09)60259-2

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

0.0

()

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details