Neurofibromatosis is an autosomal dominant disorder that affects the bone, nervous system, soft tissue, and skin. At least 8 different clinical phenotypes of neurofibromatosis have been identified that are associated with at least two genetic disorders. Clinical manifestations increase over time. Neurological and developmental problems toward malignancy might come afterwards.
Neurofibromatosis type 1 have varying phenotypic expression including dermatologic manifestations. Some patients may have a particular expression of the skin, while others may have life-threatening complications.
A neurocutaneous condition, neurofibromatosis may involve almost any organ system. Thus, the signs and symptoms can vary widely demonstrated. Two major subtypes exist: neurofibromatosis type 1, also known as von Recklinghausen neurofibromatosis, which is the most common subtype and is referred to as the neurofibromatosis, and neurofibromatosis type 2, the so-called central neurofibromatosis is a genetic disorder associated with bilateral vestibular schwannomas multisystem, schwannomas spinal cord, meningiomas, gliomas, and juvenile cataracts, skin with lack of features.
II. A. DEFINITION
Neurofibromatosis is a genetic disorder that interferes with the growth of cells in the nervous system, causing tumors to form in nerve tissue. These tumors can occur anywhere in the nervous system, including the brain, spinal cord, and nerves of large and small. Neurofibromatosis is usually diagnosed in childhood or early adulthood.
II. 2. Etiology
What causes neurofibromatosis has not been fully explained, but it seems mostly due to genetic defects (mutations) are passed down from parents or occur spontaneously at conception. Any form of neurofibromatosis is caused by mutations in different genes. The comparison NF1 = 1/3000 births and NF2 = 1/120, 000 births.
Neurofibromatosis is represented by a genetic disorder are summarized in three clinical forms of neurofibromatosis type 1 (NF1) Neurofibromatosis type 2 (NF2) and Schwannomatose, which is autosomal dominant with similar appearance of multiple benign tumors of the nervous system. Is progressive and unpredictable.
Neurofibromatosis 1 (NF1)
NF1 gene located on chromosome 17, this gene produces a protein called neurofibromin, which is usually abundant in the nervous system tissue to act as oncogenes and tumor suppressor. Lack both copies of the gene induces the growth of various neoplasms and non-neoplastic lesions. The main target organ of both the peripheral (PNS) and central (CNS) nervous system and skin, but most are widespread and can occur multiple organ system involvement. Typically, a mutation of the NF1 gene cause the loss of neurofibromin, which allows cells to grow uncontrolled. This causes the characteristic of NF1 tumors.
Neurofibromatosis 2 (NF2)
A similar problem occurs with NF2. NF2 gene located on chromosome 22, which produces a protein called merlin. A mutation of the NF2 gene lead to loss of merlin, which also leads to uncontrolled cell growth.
Because schwannomatosis recently been identified as a separate type of neurofibromatosis, the exact cause is still under study. In a small number of familial cases, have been associated with gene mutations SMARCB1/INI1, but in many cases the cause is unknown. Schwannomatosis more spontaneous occurrence (sporadic) rather than inheritance.
• Autosomal dominant inheritance pattern
In autosomal dominant disorder, the mutated gene is a dominant gene located on one of the nonsex chromosomes (autosomes). Only need one mutated gene that will be affected by the type of disorder. A person with an autosomal dominant disorder - in this case, the father - has a 50 percent chance of having an affected child with one mutated gene (dominant gene) and a 50 percent chance of having an affected child with two normal genes (recessive genes).
• The greatest risk factor for neurofibromatosis is a family history of this disorder. About half of the NF1 and NF2 cases are inherited. The remaining cases result from spontaneous mutations that occur at fertilization.
• NF1 and NF2 are both autosomal dominant disorder, which means that every child of the parent with the disorder have a 50 percent chance of inheriting a genetic mutation.
• The pattern of inheritance for schwannomatosis is less clear. The researchers now estimate that the risk of schwannomatosis inherited from an affected parent is about 15 percent.
II. 3. SYMPTOMS
Three different types of neurofibromatosis exist, each with signs and symptoms are different.
Neurofibromatosis 1 (NF1)
NF1 is also called von Recklinghausen disease. The disorder is transmitted in an autosomal dominant with variable expression between different families, different individuals of the same family and between different segments of the same individual .. This is neuroctodermose, which manifests as changes in the skin called "cafe au lait spots" can be an increase in the size and number in accordance with increasing age. and have different classifications: neurocutaneous disease, facomatose, neurocristopathy syndrome, and hereditary cancer syndromes macrossômica.
NF1 usually appears in childhood. Signs and symptoms include:
• Flat, brown spots on the skin. These spots are harmless, also called cafe au lait spots (ka-LAY oh Fay) with well defined, and there are spots especially in the inguinal and axillary, with sizes between 1mm to 3mm and usually grow in groups and overlapping in the skin. If there are any number of more than six pieces, this is a strong indication for NF1. With NF1, cafe au lait spots are usually present at birth or appear during the first year of life. Their numbers tend to increase in early childhood and then stabilized. This is not serious but sometimes it can be a cosmetic concern.
image: café au lait
cafe au lait macules of neurofibromatosis have a light brown color, and even with a smooth boundary. The presence of neurofibromas in the upper right and lower left corner of photo to make a diagnosis of neurofibromatosis is almost sure.
• freckling in the armpit or groin area known as Crowe sign, is a helpful diagnostic features in neurofibromatosis. . They occur in 4 to 5 years. Axillary freckling and inguinal freckling often develop during puberty. Development of the spots are often followed the development of café au lait macula, but precede the development of neurofibromas. Eighty percent of patients with neurofibromatosis type 1 has freckling of the axillae. Area of freckling and regions hypertrichosis occasionally overlay plexiform neurofibromas.
• neurofibromas are the most common benign tumors of neurofibromatosis type 1. These tumors are composed of Schwann cells, fibroblasts, mast cells, and vascular components.
Soft lump on or under the skin (neurofibromas). These are benign tumors that grow on nerve tissue near the skin. Sometimes, the growth would involve several nerves (plexiform neurofibroma).
Neurofibromas can develop at any point along the nerve. There are three subtypes of neurofibromas: skin, subcutaneous, and plexiform. Lesions confined to the skin and subcutaneous lesions; also not specific to the type 1 neurofibromatosis. These nodules may be brown, pink, or flesh-colored. palpable soft if aisentuh, and may have a pathognomonic figure invagination when pressed with finger.
Neurofibromas increase in number and size over time. Neurofibromas Soft myoma shown here is in the arms of a woman with neurofibromatosis type 1. Neurofibromas soft on palpation, and palpable neurofibromas soft on palpation, and showed signs of the figure, which can be pushed It was deeper into the dermis. low-power view of a neurofibroma reveals spindled cells in the dermis (hematoxylin and eosin)).
Demarcated discrete neurofibromas with focal masses that usually appears at puberty and may be associated with pruritus. Plexiform involves several branches or fasikula nerves, and can cause excessive growth, with malignant degeneration of peripheral nerve sheath tumors - which can be classified as diffuse or nodular.
Plexiform neurofibroma is noncircumscribed, thick, and irregular, and they can cause structural damage to the important support structures wrapped around. Plexiform subtype is specific for type 1 neurofibromatosis.
Lisch nodules are the most common type of ocular involvement in NF-1. These nodules are melanocytic hamartomas are nodules, usually clearly visible yellow to brown, which appears as a well-defined, dome-shaped projection of the increase of the surface of the iris. Lisch nodules can be seen without magnification, but slit lamp examination may be required to distinguish them from nevi of the iris, which is present as a flat or a minimal height, densely pigmented lesions with blurred margins. Nodules are not thought to cause ophthalmologic complications.
Lisch nodules are the most common clinical findings in adults older than 20 years with NF-1. Unlike the café-au-lait spots, multiple nodules specifically for peripheral NF/NF-1. Lisch nodules are generally in the center NF/NF-2 and has the following characteristics:
• specific to NF-1
• Smooth, usually bilateral, increased nodule
• Usually occurs in the first decade, almost all patients with NF-1 have Lisch nodules by age 20 years
• Benign hamartomas, histologically identical with iris nevi, typical appearance of multiple Lisch nodules in several appearances in patients with neurofibromatosis.
The following is a characteristic of plexiform neurofibroma eyelid:
• Thickening of the top cover
• S-shaped deformity
• Sensation "bag of worms"
Congenital glaucoma ipsilateral to plexiform neurofibromas has been described as a variety of anterior segment developmental disorders.
Hamartomas of the choroid has the following characteristics:
• Usually in the posterior pole
• Flat, no obvious lesions
• Contains components of neuronal and melanocytic
Optic nerve gliomas
Prominent corneal nerves
• Bone defects. Abnormalities in bone growth and bone mineral density and lack of muscle imbalance can cause neurogenic skeletal deformities such as spinal curvature (scoliosis dysplastic), bent due to the lower limbs and tibial pseudoarthrosis ossifikasi fibroma.
• disturbance and disability in learning. Disorders of intelligence (cognition) is common in children with NF1, but usually mild. Most children are in the low average range. Often, children with NF1 have a specific learning disability, such as problems with visual-spatial skills or attention-deficit/hyperactivity disorder (ADHD).
• The head is larger than average. Children with NF1 tend to have larger brain volume, but it is unknown whether this is related to cognitive impairment.
• Short stature. Short stature is another characteristic that is sometimes seen in children with NF1.
• Change of Heart as hypertension idiopathic or associated with pheochromocytoma or renal artery stenosis by neurofibromas, congenital heart disease and vascular abnormalities.
Neurofibromatosis 2 (NF2)
NF2 is more rare than NF1. Signs and symptoms of NF2 are usually the result of the development of vestibular schwannomas (also known as acoustic neuroma) in both ears. The benign tumors grow on the nerve that carries sound and balance information from the inner ear to the brain (the eighth cranial nerve).
In many cases, peripheral nerve most often involved are the ulnar nerve, radial, median, intercostal nerves, brachial pelxo branches and roots of cauda equina. The affected cranial nerves are the most frequent acoustic nerve and may have bilateral involvement, trigeminal and vagus nerves may also be involved more frequently.
Clinical manifestations of NF2 including hearing loss, ringing in the ears, and balance problems related to the vestibular nerve lesion. Individuals at risk for NF2 should be screened carefully for early signs of hearing loss, motor or sensory changes, and visual deficits.
Skin manifestations are much less frequent in NF2 than in NF1. CNS lesions that develop in nearly all affected individuals. Cranial nerve palsy can be derived from the adjacent nerve compression secondary to a vestibular schwannoma wide or directly from cranial nerve schwannomas nonvestibular, including: intracranial tumor Schwann cells and meninges, intracranial calcification nontumoral (choroid plexus), and neoplasms of the spinal nerve roots and nerves (especially ependymomas, schwannomas and meningiomas).
The resulting signs and symptoms usually appear in late adolescence and early adulthood, and include:
• Hearing loss is gradual
• The voice ringing in the ears (Tinnitus)
• Lack of balance
• In some cases, NF2 can lead to growth in the nerves of the body, including, skull, spine, vision (optic) and peripheral nerves. The signs and symptoms such as:
manifestations may occur in the retina of the eye fácomo which is equivalent to a small tumor of skin and nerve tumors. Fácomos looks like a circular white patch, and atrophy of the optic nerve or chiasm glioma,
Numbness and weakness in arms or legs
Distinguish between relatively common clinical NF1 and NF2 this step is sometimes problematic. Patients with NF2 almost never have a large number of cafe-au-lait spots (although in rare cases, 6 or more can be seen), while the cafe-au-lait spot a lot and everywhere in the case of NF1. Both spots are axillary or inguinal common occurrences in NF2.
Malignant transformation of benign growths almost unheard of in NF2, unlike in NF1. However, individuals with NF1 or NF2 can develop multiple subcutaneous lesions that may be clinically indistinguishable (see figure below). In NF2, the lesion is most commonly defined as histologically or neurilemomas schwannomas, whereas in NF1 is defined histologically as neurofibromas. Subcutaneous neurofibromas are occasional findings in NF2.
A: subcutaneous and skin lesions on a young man with neurofibromatosis type 2; note: cafe-au-lait spot less. B: Right neck mass in patients with neurofibromatosis type 2. C: Facial asymmetry, OS proptosis and exotropia, as well as multiple subcutaneous lesions on the forehead and face, on a 20-year man with neurofibromatosis type 2. D: Posterior cervical cord scar of resection of the lesion, scoliosis chest, and subcutaneous mass in young adults with neurofibromatosis type 2.
Posterior subcapsular lenticular opacities, although at the age of the children, would indicate the presence of NF2, whereas Lisch nodules be diagnostic as NF1. Finally, although individuals with NF1 or NF2 can either develop into spinal cord tumors, schwannomas are common in NF2, whereas neurofibromas seen primarily in NF1.
Schwannomatosis is a rare form of neurofibromatosis was discovered. It mostly seems to affect people in their 20s and 30's. Schwannomatosis that causes tumors called schwannomas growing on cranial nerves, spinal cord and peripheral nerves, but not on the nerve that carries sound and balance information from the inner ear to the brain (the eighth cranial nerve), so it does not cause hearing loss, making distinct from NF2 . Such as NF2, though, schwannomatosis do not cause cognitive impairment. The main symptom of schwannomatosis are: chronic pain, which can occur in all parts of the body.
II. 4. TEST AND DIAGNOSIS
Depending on the type of neurofibromatosis suspected
Physical examination and health history. NF1 is usually diagnosed based on a thorough physical examination, examine the characteristics of typical NF1 by using a special lamp to check skin-colored cafe au lait spots. Family history of NF1 or NF2 can help confirm the diagnosis.
• eye examinations. Which can detect the presence of small bumps on the iris (Lisch nodules) and cataracts.
A: Histopathology section showing clumps of melanocytes Lisch nodules (white arrows) in the stroma of the iris (hematoxylin and eosin, magnification × 100).
B: Histopathology of the eyes of patients with neurofibromatosis-1 with congenital glaucoma. White arrow indicates the nerve sclerocorneal prominent. Black arrow indicates angle dysgenesis, no trabecular meshwork or Schlemm canal could be identified. Yellow arrows indicate ciliochoroidal hyperplasia (hematoxylin and eosin, magnification × 40).
eye examination for lens opacities, retinal hamartomas, or epiretinal membrane may be very useful even in children who are at risk for neurofibromatosis type 2 (NF2).
• Examination of the ear. Hearing and balance tests such as audiometry tests, electronystagmography and auditory brain stem response can help determine the level of hearing and balance function in people with NF2.
• imaging tests, like X-ray, CT scan and MRI, are not always necessary, but this examination can help identify abnormalities of bone, brain tumor or spinal cord, and the tumor is very small. This may be especially helpful for NF2 and schwannomatosis.
A: large facial deformities in very young girls affected by neurofibromatosis-1.
B: Three-dimensional (3-D) computed tomography (CT) at a very young girl affected by neurofibromatosis-1. This picture shows the skull deformity. Note the presence of greater wing of sphenoid bone and enlargement of the infraorbital foramen.
A: Meningioma to the left of the midline in patients with neurofibromatosis type 2. B: Some of the meningioma (left) on the surface of the brain in patients with neurofibromatosis type 2. C: Bilateral acoustic neuromas in patients with neurofibromatosis type 2. D: Bilateral acoustic neuromas and meningiomas left side in patients with neurofibromatosis type 2. Ependymoma in patients with small neurofibromatos. E: Small ependymoma in patients with neurofibromatosis type 2. F: Some of meningiomas in patients with neurofibromatosis type 2.
• Examination of Histology, contrast with tumors associated with neurofibromatosis type 1 (NF1), which is found in NF2 are usually composed of one of three types of cells, ie Schwann cells, glial cells, or meningeal cells. Although the NF2 tumor can be locally invasive and cause significant morbidity as a result of pertumbuhanya nature, but they rarely (if ever) had a malignant transformation. This is somewhat different than in NF1, plexiform neurofibroma which sometimes develop into neurosarcomas.
However, vestibular schwannomas and meningiomas in NF2 tend to be more aggressive than in the case of sporadic tumors (ie, they are not associated with NF2), with a broader trend of local invasion and the histological evidence of increased mitosis.
• genetic tests. Genetic testing is available for NF1, NF2 and schwannomatosis and can be done before birth.
CRITERIA FOR TYPE 1 neurofibroma DIAGNOSTICS
In the diagnosis the patient must have two or more criteria developed by the Consensus Development Conference (1988), these criteria have high sensitivity and specificity, especially in adults.
• 6 or more spots where coffee with milk with a size greater than 5 mm in prepubertal subjects or greater than 15mm after puberty;
• 2 or more neurofibromas of any type or one plexiform neurofibroma or more;
• Freckles axillary or inguinal;
• Glioma optic nerve
• 2 or more Lisch nodules;
• A typical lesions such as the wing of the sphenoid bone dysplasia
• The first level relative with NF1
II. 5. DIAGNOSIS
Neurofibromatosis type 1
• Brainstem gliomas
• Medullaris Conus cauda equina and Syndromes
• Low-grade astrocytoma
• Neurofibromatosis, Type 2
• Spinal Cord Hemorrhage
• Spinal Cord Infarction
• Spinal Epidural Abscesses
Neurofibromatosis type 2
• Glioma brainstem
• Neurofibromatosis, Type 1
II. 6. COMPLICATIONS
Complication of neurofibromatosis varies, even within the same family. Generally, complications resulting from the growth of nerve tissue or a tumor pressing on internal organs.
most people with neurofibromatosis have mild or moderate impairment, regardless of type. Typically, serious complications develop before adolescence.
Neurofibromatosis 1 (NF1)
Common complications of NF1 include:
• neurological problems. Learning difficulties can occur up to 60 percent of cases of NF1 and neurological problems are most commonly associated with NF1. Rare neurological complications associated with NF1, including epilepsy, stroke and excessive fluid buildup in the brain (hydrocephalus) due to stenosis of the aqueduct of Sylvius and the death of craniofacial malformations, for example, the upper eyelid plexiform neurinomios, neurofibroma primitive orbit ..
• Impaired performance can be seen as symptoms of neurofibromatosis. such as the extent of cafe au lait spots, neural tumors (neurofibromas) on the face or neurofibromas large - can lead to anxiety and emotional distress, even though not a serious medical problem.
• bone problems. Some children have experienced abnormal shape of bones, which can cause a curved spine (scoliosis) and bowed legs. NF1 is also associated with decreased bone mineral density, which increases the risk of brittle bones (osteoporosis).
• visual difficulties. Rarely occurs in children, the tumors grow on nerves leading from the eye to the brain (optic nerve) can cause vision problems.
• Increased neurofibromas. Hormonal changes associated with puberty, pregnancy or menopause can cause an increase in neurofibroma. Most women with NF1 have a healthy pregnancy but will probably need to be monitored by an obstetrician who know about NF1, in addition to its specialist NF1.
• Cardiovascular Problems People with NF1 have an increased risk of high blood pressure and abnormal blood vessels.
• Cancer. Less than 10 percent of people with NF1 develop into cancer (malignant). These usually arise from plexiform neurofibroma or subcutaneous neurofibroma involving multiple nerves. Monitoring neurofibroma watch for any changes in appearance, size or number. Changes may indicate cancer growth. Malignancy is detected early will give better treatment effectiveness. People with NF1 also have a higher risk for cancer occurrence in other forms, such as breast cancer, leukemia, brain tumors and some types of soft tissue cancers.
Neurofibromatosis 2 (NF2)
Expansion of the tumor in people with NF2 can lead to:
• Deaf partially or completely
• Damage to the facial nerve
• visual disturbances
• Weakness or numbness in the extremities
• Multiple benign brain tumor (meningioma) that require frequent operations.
• Meningiomas, gliomas, ependymomas, and other lesions in the brain, cerebellar and spinal cord can cause neurological deficits, seizures, and / or hydrocephalus.
Pain caused by schwannomatosis may weaken and may require surgical treatment.
II. 7. TREATMENT AND MEDICINES
The main treatment for neurofibromatosis is monitoring for complications, which are often conducted by a team of specialists in a neurofibromatosis clinic, and appropriate treatment begins as early as possible.
If signs of NF1, the monitoring is done every year in the form:
• Assess skin neurofibroma of new or changes that occur
• Check your blood pressure for signs of high blood pressure
• Evaluate the growth and development - including height, weight and head circumference according to growth charts are available for children with NF1
• Evaluate the change order and abnormalities
• Assess the development and advancement of learning in schools
• Perform a complete eye examination
Children with NF1 reached adulthood, the frequency of monitoring can be tailored to meet the needs of people with NF1. Adults with mild disease may not require monitoring as often as those with more severe complications.
There is no effective medical therapy is known to neurofibromatosis type 2 (NF2). However, in rare cases where surgical resection of symptomatic ependymomas is not possible, chemotherapy with lomustine, vincristine, and prednisone, or carboplatin and vincristine, subsequent radiation therapy, can serve as a palliative function.
The use of erlotinib therapy has shown promise in the treatment of non-surgical, progressive vestibular schwannomas, so not only in a decrease in tumor size but also in the improvement of hearing function. Further clinical trials are in order prior to use of oral chemotherapy agents can be recommended routinely.
At the beginning of in vitro studies showed that Gleevec, a tyrosine kinase inhibitor, is useful in the treatment of vestibular, spinal cord and spinal schwannomas in patients with NF2
SURGERY AND OTHER PROCEDURES
• Surgery to remove all or part of the tumor pressing on nearby tissue or organ damage may help relieve symptoms. This applies to all forms of neurofibromatosis. Complete removal of schwannomas in schwannomatosis can ease the pain substantially. However, it is important to discuss the pros and cons of surgery in treating nerve tumor, because tumors often grow back and operate in the same area and probably will grow not as worthy as the first and surgery for removal of vestibular schwannoma may present a risk of total hearing loss or damage the facial nerve.
• Stereotactic radiosurgery can be an option for those with NF2 and vestibular schwannoma. This procedure is done by giving precise radiation on the tumor location and can help keep your hearing.
• Plastic surgery and laser therapy can be used to remove lesions on the skin surface and to help improve the appearance.
• (Back brace) A back brace is often used to treat scoliosis. In severe cases, back surgery may also be an option.
Malignant tumors and other cancers associated with neurofibromatosis (NF1 often) treated with standard cancer therapies, such as surgery, chemotherapy and radiation therapy.
II. 8. Prognosis
Although most individuals with NF1 can live a relatively long and healthy life expectancy as a whole can be reduced as many as 15 years. The main cause for increased morbidity and mortality are hypertension, sequelae of spinal lesion, and malignancy.
Immediate attention to early detection of complications of NF1 can significantly reduce the overall morbidity and mortality rates.
Prognosis neurofibromatosis type 2 (NF2) depends on several factors, including age of onset of symptoms, degree of hearing deficit, and the number and location of various tumors. Although age of onset is relatively equal in the family, age range 2-70 years may vary. While the tumor itself is relatively slow and did not experience malignant transformation in a study conducted in the late 1980s and early 1990s clearly show that significant levels of mortality and morbidity associated with diagnosis of NF2.
One study showed that the survival of the time average of the actual diagnosis of 15 years, but this can be changed for the better with a better diagnosis, surgical techniques, monitoring, filtering,
1. Neurofibromatosis lembar fakta. National Institute of Neurological Gangguan dan Stroke. http://www.ninds.nih.gov/disorders/neurofibromatosis/detail_neurofibromatosis.htm. Diakses April 12, 2010.
2. Hersh JH, dkk. Kesehatan pengawasan untuk anak-anak dengan neurofibromatosis. Pediatrics. 2008; 121:633.
3. RE Ferner, dkk. Pedoman diagnosis dan manajemen individu dengan neurofibromatosis 1. Journal of Medical Genetics. 2007; 44:81.
4. Williams VC, dkk. Neurofibromatosis tipe 1 ditinjau kembali. Pediatrics. 2009; 123:124.
5. Savar A, Cestari DM. Neurofibromatosis tipe I: genetika dan manifestasi klinis Semin Ophthalmol.. Jan-Feb 2008; 23 (1) :45-51. [Medline] .
6. Listernick R, Charrow J, Greenwald MJ, Esterly NB. Optik glioma pada anak dengan neurofibromatosis tipe 1. J Pediatr. Mei 1989; 114 (5) :788-92. [Medline] .
7. Glaser JS, Hoyt WF, J. Corbett morbiditas Visual dengan glioma chiasmal. Studi jangka panjang bidang visual dalam kasus yang tidak diobati dan iradiasi. Arch Ophthalmol. Jan 1971; 85 (1) :3-12. [Medline] .
8. Torpy JM, et al. JAMA pasien halaman. Neurofibromatosis. JAMA. 2009; 302:2170.
9. Apakah NF? Neurofibromatosis, Inc http://www.nfinc.org/what.shtml. Accessed December 16 Desember 2010.
10. Diagnostik kriteria untuk NF-2. Neurofibromatosis, Inc http://www.nfinc.org/nf2.shtml. Accessed December 16 Desember 2010.
11. Diagnostik kriteria untuk NF-1. Neurofibromatosis, Inc http://www.nfinc.org/nf1.shtml. Accessed December 16 Desember 2010.
12. Plon SE, dkk. Neurofibromatosis tipe 1 (penyakit von Recklinghausen ini). http://www.uptodate.com. Diakses April 12, 2010.
13. Ferner RE. Neurofibromatosis 1 dan neurofibromatosis 2: Sebuah perspektif abad dua puluh satu. Lancet Neurology. 2007; 6:340.
14. Schwannomatosis. Anak Tumor Foundation. http://www.ctf.org/living-with-nf/schwannomatosis.html. Diakses April 18, 2010.
15. MacCollin M, dkk. Diagnostik kriteria untuk schwannomatosis. Neurology. 2005; 64:1838.
16. Diagnosis NF1. Anak Tumor Foundation. http://www.ctf.org/Living-with-NF/diagnosis-of-nf1.html Halaman 1 dari. Diakses April 18, 2010.
17. Neurofibromatoses. March of Dimes. http://www.marchofdimes.com/pnhec/4439_1217.asp~~V. Diakses April 18, 2010.
18. Carey JC, DH Viskochil. Neurofibromatosis tipe 1: kondisi model untuk mempelajari dasar molekul expressivity variabel pada gangguan manusia. Am J Med Genet 1999, 89:7-13.
19. BR Korf Keganasan pada neurofibromatosis tipe 1. Para Onkologi 2000, 5:477-85.
20. Dasgupta B, Gutmann DH Neurofibromatosis 1: menutup Gap Antara tikus dan manusia. Curr Op Gen Dev 2003; 13:20-7.
21. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE et al. Evaluasi diagnostik dan manajemen multidisiplin neurofibromatosis 1 dan neurofibromatosis 2. JAMA 1997; 278:51-7.
22. Hanemann CO. Magic but treatable? Tumours due to loss of merlin. Brain. Mar 2008;131:606-15.
23. Fisher LM, Doherty JK, Lev MH, et al. Distribution of nonvestibular cranial nerve schwannomas in neurofibromatosis 2. Otol Neurotol. Dec 2007;28(8):1083-90. [Medline].
24. Lee HBH, Garrity JA, Cameron JD, Strianese D, Bonavolonta G, Patrinely JR. Primary optic nerve sheath meningioma in children. Surv Ophthalmol. 2008;53:543-58.
25. Sestini R, Provenzano A, Bacci C, et al. NF2 mutation screening by denaturing high-performance liquid chromatography and high-resolution melting analysis. Genet Test. Jun 2008;12(2):311-8. [Medline].
26. Harris GJ, Plotkin SR, Maccollin M, et al. Three-dimensional volumetrics for tracking vestibular schwannoma growth in neurofibromatosis type II. Neurosurgery. Jun 2008;62(6):1314-9; discussion 1319
27. Selch MT, Pedroso A, Lee SP, et al. Stereotactic radiotherapy for the treatment of acoustic neuromas. J Neurosurg. Nov 2004;101 Suppl 3:362-72.
28. Otto SR, Brackmann DE, Hitselberger W. Auditory brainstem implantation in 12- to 18-year-olds. Arch Otolaryngol Head Neck Surg. May 2004;130(5):656-9.
29. Mukherjee J, Kamnasaran D, Balasubramaniam A, et al. Human schwannomas express activated platelet-derived growth factor receptors and c-kit and are growth inhibited by Gleevec (Imatinib Mesylate). Cancer Res. Jun 15 2009;69(12):5099-107.
30. von Eckardstein KL, Beatty CW, Driscoll CL, Link MJ. Spontaneous regression of vestibular schwannomas after resection of contralateral tumor in neurofibromatosis Type 2. J Neurosurg. Jan 2010;112(1):158-62.
31. Safavi-Abbasi S, Bambakidis NC, Zabramski JM, et al. Nonvestibular schwannomas: an evaluation of functional outcome after radiosurgical and microsurgical management. Acta Neurochir (Wien). Jan 2010;152(1):35-46.
32. Gerszten PC, Burton SA, Ozhasoglu C, McCue KJ, Quinn AE. Radiosurgery for benign intradural spinal tumors. Neurosurgery. Apr 2008;62(4):887-95; discussion 895-6.
33. Schwartz MS, Otto SR, Shannon RV, et al. Auditory brainstem implants. Neurotherapeutics. Jan 2008;5(1):128-36.