Neurofibromatosis type I - Knowledge (XXG)

68: 266: 1036: 474:, are hyper pigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means "coffee with milk". The borders may be smooth or irregular. These spots can grow from birth and can continue to grow throughout the person's lifetime. They can increase in size and numbers during puberty and during pregnancies. They are present in about 99% of patients of European origin and in about 93% of patients of Indian origin. 916:. Malignant nerve sheath tumor was the main cause of death (60%) in a study of 1895 patients with NF-1 from France in the time period 1980–2006 indicated excess mortality in NF-1 patients compared to the general population. The cause of death was available for 58 (86.6%) patients. The study found excess mortality occurred among patients aged 10 to 40 years. Significant excess mortality was found in both males and females. 255: 451:, where growth at the epiphyseal (growth) plate is halted. It can be performed on one side of the bone to help correct an angular deformity, or on both sides to stop growth of that bone completely. The surgery must also be carefully planned with regard to timing, as it is non-reversible. The goal is that the limbs are at near-equal length at end of growth. 999:

caused a mutation in the neurofibromin gene, leading to the NF1 phenotype. Two recurrent microdeletion types with microdeletion breakpoints located in paralogous regions flanking NF1 (proximal NF1-REP-a and distal NF1-REP-c for the 1.4 Mb type-1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Mb type-2 microdeletion), are found in most cases.

670: 622:: Often congenital. Lesions are composed of sheets of neurofibromatous tissue that may infiltrate and encase major nerves, blood vessels, and other vital structures. These lesions are difficult and sometimes impossible to routinely resect without causing any significant damage to surrounding nerves and tissue. 446:

Unilateral overgrowth of a limb. When a plexiform neurofibroma manifests on a leg or arm, it will cause extra blood circulation, and may thus accelerate the growth of the limb. This may cause considerable difference in length between left and right limbs. To equalize the difference during childhood,

1211:

For many NF-1 patients, a primary concern is the disfigurement caused by cutaneous/dermal neurofibromas, pigmented lesions, and the occasional limb abnormalities. However, there are many more severe complications caused by NF-1 like increased cancer risk, a plexiform neurofibroma has a 10-15% chance

1155:

Treatment for NF1 is limited, and there is currently no cure. Pain meds can be prescribed to help with pain. In some cases, growths may be removed surgically or reduced with radiation therapy. Treatment options are limited, given the tumours tendency to regrow following surgery and their propensity

835:

People with NF1 are at increased risk for experiencing social and emotional difficulties such as; anxiety, depression, low self-esteem and/or body image, social withdrawal, difficulty forming interpersonal relationships, behavioural problems, and difficulties in school. People with NF1 are much more

542:

The most common complication in patients with NF-1 is cognitive and learning disability. These cognitive problems have been shown to be present in approximately 90% of children and adults with NF-1 and have significant effects on their schooling and everyday life. These cognitive problems have been

273:

The following is a list of conditions and complications associated with NF-1, and, where available, age range of onset and progressive development, occurrence percentage of NF-1 population, method of earliest diagnosis, and treatments and related medical specialties. The progression of the condition

1176:

sold under the brand name Koselugo, and was approved by the FDA in April 2020 for the treatment of NF-1 in the pediatric population who are two or more years of age. It is a mitogen-activated protein kinase inhibitor (MEKi) and is indicated for use in pediatric patients who are symptomatic and have

871:

Children diagnosed with NF-1 may experience delayed or precocious puberty. Recent studies have correlated precocious puberty in individuals with NF-1 with the presence of optic pathway tumours. Furthermore, the heights of children affected by NF-1 have been shown to increase normally until puberty,

408:

family of diseases, which include Costello Syndrome, Noonan Syndrome, and Cardiofaciocutaneous syndrome. The RASopathies also present with skeletal muscle weakness. It is likely that impaired muscle function in these disorders is linked to altered Ras/MAPK signalling, however, the precise molecular

236:

The severity of NF-1 varies widely, and little is known about what causes a person to have more severe or less severe symptoms. Even within the same family (as there is a 50% chance that a parent will pass their condition to their offspring), levels of severity can vary enormously. However, 60% of

998:

In 1989, through linkage and cross over analyses, neurofibromin was localized to chromosome 17. It was localized to the long arm of chromosome 17 by chance when researchers discovered chromosome exchanges between chromosome 17 with chromosome 1 and 22. This exchange of genetic material presumably

836:

likely to experience suicidal thoughts than the general population. One study found that 45% of people with NF had suicidal thoughts compared to 10% of a healthy control group. Another study found that 46.5% were of people with NF1 were found to have at least one psychiatric comorbid diagnosis.

1007:

The neurofibromin gene was soon sequenced and found to be 350,000 base pairs in length. However, the protein is 2818 amino acids long leading to the concept of splice variants. For example, exon 9a, 23a and 48a are expressed in the neurons of the forebrain, muscle tissues and adult neurons

1011:

Homology studies have shown that neurofibromin is 30% similar to proteins in the GTPase activating protein (GAP) family. This homologous sequence is in the central portion of neurofibromin and being similar to the GAP family is recognized as a negative regulator of the

2523:

Chisholm, Anita K.; Haebich, Kristina M.; Pride, Natalie A.; Walsh, Karin S.; Lami, Francesca; Ure, Alex; Maloof, Tiba; Brignell, Amanda; Rouel, Melissa; Granader, Yael; Maier, Alice; Barton, Belinda; Darke, Hayley; Dabscheck, Gabriel; Anderson, Vicki A. (2022-01-04).

1106:

over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. Note that multiple café-au-lait spots alone are not a definitive diagnosis of NF-1 as these spots can be caused by a number of other

794:, pons, midbrain, globus pallidus, thalamus, and optic radiations. Their exact identity remains a bit of a mystery since they disappear over time (usually, by age 16), and they are not typically biopsied or resected. They may represent a focally degenerative bit of 1156:

to transform into malignant tumours following radiation. Although surgery in these areas can cause further injury to nerves and additional neurological problems. The benefits of surgery should always be considered against its risks. Some NF tumours are inoperable.

1097:

The National Institutes of Health (NIH) has created specific criteria for the diagnosis of NF-1. Two of these seven "Cardinal Clinical Features" are required for positive diagnosis. There is practical flowchart to distinguish between NF1, NF2 and schwannomatosis.

5056: 245:

patients have moderate cases, with several symptoms that have little more than cosmetic effects. The other 20% have severe cases, with several symptoms that affect the person's quality of life. Even in this last group, symptoms are rarely life-threatening.

543:

shown to be stable into adulthood mainly in the mid 20s to early 30s and do not get worse unlike some of the other physical symptoms of NF-1. The most common cognitive problems are with perception, executive functioning and attention. Disorders include:

4171: 3612: 3592: 3389:

Coltin H, Perreault S, Larouche V, Black K, Wilson B, Vanan MI, et al. (August 2022). "Selumetinib for symptomatic, inoperable plexiform neurofibromas in children with neurofibromatosis type 1: A national real-world case series".

382:

Deficits in motor function in NF-1 have been long recognised and have been historically attributed to nerve dysfunction. In recent years however, studies suggest NF-1 is associated with a primary problem in muscle function (myopathy).

5049: 400:

Studies in genetically modified mice have thus far confirmed that the NF1 gene is vital for normal muscle development and metabolism. Knockout of the NF1 gene in muscle results in deregulated lipid metabolism and muscle weakness.

1184:, fatigue, muscle pain, Constipation, Paronychia as well as dry skin and other skin and hair problems. The side effects can have a significant impact on a patient's life and may lead to someone having to discontinue treatment. 929:

and may have an increased breast cancer related mortality. The median survival for breast cancer in people with NF was 5 years vs. the reported median survival of over 20 years in the general population using the SEER database.

1027:. Together, likely with domains yet to be discovered, neurofibromin regulates many of the pathways responsible for overactive cell proliferation, learning impairments, skeletal defects and plays a role in neuronal development. 820:

pulsation, and typically presents as paraesthesia or loss of motor or sensory function. It has been shown that dural ectasia occur near plexiform neurofibromas which may be infiltrative leading to weakening of the dura.

5831: 5042: 586:

is a rare condition defined by the presence of multiple benign tumors of nerves that are frequently very painful. In addition to pain, weakness is a common problem. Symptoms usually begin in young or mid-adult years.

1203:

NF-1 is a progressive and diverse condition, making the prognosis difficult to predict. The NF-1 gene mutations manifest the disorder differently even amongst people of the same family. This phenomenon is called

2353:

Berardelli, Isabella; Maraone, Annalisa; Belvisi, Daniele; Pasquini, Massimo; Giustini, Sandra; Miraglia, Emanuele; Iacovino, Chiara; Pompili, Maurizio; Frascarelli, Marianna; Fabbrini, Giovanni (November 2021).

418: 5009: 4909: 4627: 4568: 1085:

People with NF-1 have a 50% percent chance of passing the disorder to their offspring, but people can have a child born with NF-1 when they themselves do not have the condition. This is caused by a

2955:

Marchuk DA, Saulino AM, Tavakkol R, Swaroop M, Wallace MR, Andersen LB, et al. (December 1991). "cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product".

2797:

Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, et al. (July 1990). "Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients".

461: 494:, manifested as single or multiple firm, rubbery bumps of varying sizes on a person's skin. Age of onset is puberty. Progressive in number and size. Not malignant. Can be treated with 3847: 2409:

Brar, Kanwarjeet S.; Trivedi, Chintan; Kaur, Navdeep; Adnan, Mahwish; Patel, Hiren; Beg, Uzma; Qureshi, Mustafa; Mansuri, Zeeshan; Ibrahim, Aalamgeer; Zafar, Muhammad K. (2023-10-03).

1993:

Hyman SL, Gill DS, Shores EA, Steinberg A, Joy P, Gibikote SV, North KN (April 2003). "Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1".

646:, peripheral nerve-sheath tumors which are seen with increased frequency in NF-1. The major distinction between a schwannoma and a solitary neurofibroma is that a schwannoma can be 5811: 1208:. For example, some individuals have almost no symptoms, while others may have a manifestation that is rapidly more progressive and can lead to significant disability and death. 533:

can cause bulging of the eyes, involuntary eye movement, squinting, and / or vision loss. Treatment may include surgery, radiation +/- steroids, or chemotherapy (in children).

2261:

Polster SP, Dougherty MC, Zeineddine HA, Lyne SB, Smith HL, MacKenzie C, et al. (May 2020). "Dural Ectasia in Neurofibromatosis 1: Case Series, Management, and Review".

2585:

Virdis, R et al. "Growth and Pubertal Disorders in Neurofibromatosis Type 1." Journal of pediatric endocrinology & metabolism : JPEM. 16 Suppl 2 (2003): 289–292. Print.

4304: 656:

Bones, especially the ribs, can develop chronic erosions (pits) from the constant pressure of adjacent neurofibroma or schwannoma. Similarly, the neural foramen of the

5841: 3972: 1293: 4540: 3434: 786:

Another CNS manifestation of NF-1 is the so-called "unidentified bright object" or UBO, which is a lesion which has increased signal on a T2 weighted sequence of a

660:

can be widened due to the presence of a nerve root neurofibroma or schwannoma. Surgery may be needed when NF-1 related tumors compress organs or other structures.

1194:

After 1 year of treatment, the mean decrease in child-reported tumour pain-intensity scores was 2 points, which is considered a clinically meaningful improvement

872:

after which increases in height lessen when compared to healthy counterparts. This eventually causes a shorter stature than expected in individuals with NF-1.

3138:"The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway" 4872: 1360: 1261: 396:

Muscle weakness (The most recent study reports between 30–50% reduced upper and lower limb muscle strength in NF-1 children compare with matched controls).

1082:

While the presence of NF-1 can be identified through prenatal testing the severity with which the condition will be expressed is impossible to determine.

5589: 4441: 4278: 373:

are the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately 25% of patients will require corrective surgery.

3980: 3497: 5441: 4487: 3985: 1883: 849: 554: 1535: 5768: 4993: 4917: 4841: 4161: 3811: 2088:

Thompson HL, Viskochil DH, Stevenson DA, Chapman KL (February 2010). "Speech-language characteristics of children with neurofibromatosis type 1".

884: 816:, which is the tough covering of the brain and spine. Weakness of the dura leads to focal enlargement due to chronic exposure to the pressures of 747:. Electroencephalograph, magnetic resonance imaging, computed tomographic scan, single-photon emission CT and positron emission tomographic scan. 5187: 1807:

Stevenson DA, Allen S, Tidyman WE, Carey JC, Viskochil DH, Stevens A, et al. (September 2012). "Peripheral muscle weakness in RASopathies".

1623: 159:

As of 2015, there are at least 100,000 people in the U.S. and about 25,000 people in the UK who have been diagnosed with NF. Common symptoms of

5520: 4358: 4242: 429: 1499: 1019:

Additionally, being such a large protein, more active domains of the protein have been identified. One such domain interacts with the protein

284:

Small tumors may arise in the retina which can eventually lead to blindness. Also, Lisch Nodules may grow on the iris, but these are harmless.

4299: 3332: 1389:

Costa RM, Silva AJ (August 2002). "Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1".

3052:

Feldkamp MM, Angelov L, Guha A (February 1999). "Neurofibromatosis type 1 peripheral nerve tumors: aberrant activation of the Ras pathway".

5796: 5304: 5259: 5197: 4507: 3806: 1212:

of developing into a MPNST (Malignant Peripheral Nerve Sheath Tumour) Epidemiology NF-1 is estimated to affect around 25,000 people in the

4252: 551:, with 36.78% of them being severe cases, 33.33% being mild to moderate cases, and 29.89% of them having both symptoms of autism and ADHD. 4115: 1950:

Hyman SL, Shores A, North KN (October 2005). "The nature and frequency of cognitive deficits in children with neurofibromatosis type 1".

4679: 4533: 4002: 3627: 3225: 2648: 2631: 230: 2608: 2236: 1243:, had suffered from neurofibromatosis type 1 (NF1). In 1986, geneticists Tibbles and Cohen conjectured that Merrick was afflicted with 5658: 5128: 5108: 5118: 3995: 5673: 4080: 3852: 2410: 2180:

Vivarelli R, Grosso S, Calabrese F, Farnetani M, Di Bartolo R, Morgese G, Balestri P (May 2003). "Epilepsy in neurofibromatosis 1".

1076: 67: 5368: 5177: 5133: 4867: 3832: 3743: 3089:"Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras" 3471: 1282: 290:

Neurofibromas may occur and can sometimes cause many dependent neurological conditions and cutaneous and skeletal disfigurement.

5836: 582:

The primary neurologic involvement in NF-1 is of the peripheral nervous system, and secondarily of the central nervous system.

2724:"Increased breast cancer risk in women with neurofibromatosis type 1: a meta-analysis and systematic review of the literature" 132:

that is responsible for production of a protein (neurofibromin) which is needed for normal function in many human cell types.

5172: 5071: 4526: 4273: 4388: 1047:

The mutant gene is transmitted with an autosomal dominant pattern of inheritance, but up to 50% of NF-1 cases arise due to

5376: 5324: 5242: 4674: 4247: 4105: 3927: 570: 5594: 5192: 4846: 4446: 1449:"Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation" 628:, affecting 8–12% of patients with NF-1. This occurs in a deep nerve trunk. Diagnosis by cross-sectional imaging (e.g., 5618: 5572: 5400: 4719: 265: 4415: 650:

while sparing the underlying nerve, whereas resection of a neurofibroma requires the sacrifice of the underlying nerve.

5415: 4426: 4237: 4017: 3882: 3242: 5500: 5409: 5123: 4502: 774:

Intracranially, NF-1 patients have a predisposition to develop glial tumors of the central nervous system, primarily

4351: 4125: 4090: 4070: 4022: 1177:

inoperable plexiform neurofibromas. However, this medication is not curative and is not suitable for all patients.

901: 787: 633: 221:

NF-1 is an age-specific disease; most signs of NF-1 are visible after birth (during infancy), but many symptoms of

5458: 5352: 4383: 362:

of the dura of the spine. This may result in temporary or permanent loss of lower extremity sensorimotor function.

5851: 5726: 5287: 5080: 4931: 4471: 4194: 4045: 3937: 3801: 1256: 1191:

35 patients (70%) had a confirmed partial response, 28 of these patients had a durable response (lasting ≥1 year)

5472: 5034: 1368: 5782: 5182: 5156: 4770: 4765: 4557: 4268: 3638: 2464:

Miguel, Carmen Sílvia; Chaim-Avancini, Tiffany M; Silva, Maria Aparecida; Louzã, Mario Rodrigues (2015-03-25).

305: 31: 3458: 2041:"Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study" 2296:

Cohen, Julie S.; Levy, Howard P.; Sloan, Jennifer; Dariotis, Jacinda; Biesecker, Barbara B. (November 2015).

1139:

A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without

827:

has shown promise as a treatment for this condition, and in very few cases do dural ectasia require surgery.

210:). Due to its rarity, and to the fact that genetic diagnosis has been used only in recent years, in the past 5560: 5507: 5313: 4549: 4214: 4199: 4186: 4151: 4050: 4012: 3962: 3859: 3348:

Rodrigues LO, Batista PB, Goloni-Bertollo EM, de Souza-Costa D, Eliam L, Eliam M, et al. (March 2014).

1205: 437: 195:. While some people have major complications, others with the condition can lead productive and full lives. 2466:"Neurofibromatosis type 1 and attention deficit hyperactivity disorder: a case study and literature review" 5486: 5164: 5021:

Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see

4689: 4684: 4618: 4497: 4411: 4209: 4204: 4156: 4146: 3786: 3776: 2853: 1181: 1072: 950: 560:

Speech and language delays have also been identified in approximately 68% of preschool children with NF-1.

432:

or CPT. CPT occurs in 2–4% of individuals with NF-1. Treatment includes limb amputation or correction by

229:

was formerly known as von Recklinghausen disease, after the researcher who first documented the disorder,

172: 1891: 5604: 4986: 4945: 4669: 4492: 4344: 3781: 1546: 1225: 1180:

Side effects of Selumetinib include headache, nausea/vomiting, abdominal pain and other problems of the

625: 241:

have mild cases, with few symptoms that have very little effect in their day-to-day lives. About 20% of

2673:"Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980-2006 in France" 673:

MRI image showing malignant peripheral nerve sheath tumor in the left tibia in neurofibromatosis type-1

140:

is one of the most common genetic disorders and is not limited to any person's race or sex. NF-1 is an

2671:

Duong TA, Sbidian E, Valeyrie-Allanore L, Vialette C, Ferkal S, Hadj-Rabia S, et al. (May 2011).

2223:

Listernick R, Charrow J, Gutmann DH (March 1999). "Intracranial gliomas in neurofibromatosis type 1".

1035: 604:

is a lesion of the peripheral nervous system. Its cellular lineage is uncertain, and may derive from

5846: 4950: 4760: 3736: 2806: 1624:"Sudden bilateral lower limb paralysis with dural ectasia in Neurofibromatosis type 1: A case report" 1103: 1086: 468: 258: 188: 3524:

Legendre, Claire-Marie; Charpentier-Côté, Catherine; Drouin, Régen; Bouffard, Chantal (2011-01-01).

443:

Malformation of the facial bones or of the eye sockets (lambdoid suture defects, sphenoid dysplasia)

4793: 4176: 3771: 3616: 1510: 984: 817: 647: 629: 180: 5642: 5512: 5273: 5168: 5098: 4957: 4899: 4406: 4085: 3892: 3457:

AstraZeneca Pharmaceuticals LP. Koselugo(Selumetinib). U.S. Food and Drug Administration website.

3415: 2934: 2446: 2391: 2298:"Depression Among Adults with Neurofibromatosis Type 1: Prevalence and Impact on Quality of Life" 2205: 2162: 2113: 2070: 2018: 1975: 1832: 1740: 1414: 1127: 1040: 894:. A plexiform neurofibroma has a lifetime risk of 8–12% of transformation into a malignant tumor. 775: 679: 522: 433: 199: 141: 152:, although presentation varies widely and is often different even between relatives affected by 1850:

Lakshmanan A, Bubna A, Sankarasubramaniam A, Veeraraghavan M, Rangarajan S, Sundaram M (2016).

5223: 4970: 4714: 4579: 4458: 4294: 4219: 4130: 4055: 3902: 3842: 3796: 3791: 3678: 3649: 3555: 3547: 3407: 3371: 3328: 3208: 3159: 3118: 3069: 3034: 2982: 2926: 2885: 2822: 2755: 2704: 2653: 2612: 2565: 2547: 2505: 2487: 2438: 2430: 2383: 2375: 2335: 2317: 2278: 2240: 2197: 2154: 2105: 2062: 2010: 1967: 1824: 1789: 1732: 1691: 1645: 1601: 1478: 1447:

Legius E, Messiaen L, Wolkenstein P, Pancza P, Avery RA, Berman Y, et al. (August 2021).

1406: 1342: 1020: 791: 80: 3272: 3136:

Ozawa T, Araki N, Yunoue S, Tokuo H, Feng L, Patrakitkomjorn S, et al. (November 2005).

2903:

Pasmant E, Sabbagh A, Spurlock G, Laurendeau I, Grillo E, Hamel MJ, et al. (June 2010).

269:

Diagnostic criteria of neurofibromatosis type I, requiring at least 2 of the mentioned items.

5720: 5637: 5534: 5429: 5338: 5022: 4788: 4431: 4325: 4120: 4037: 4027: 3990: 3922: 3897: 3887: 3816: 3766: 3537: 3399: 3361: 3305: 3198: 3190: 3149: 3108: 3100: 3061: 3024: 3016: 2972: 2964: 2916: 2877: 2814: 2745: 2735: 2694: 2684: 2643: 2604: 2555: 2537: 2495: 2477: 2422: 2367: 2325: 2309: 2270: 2232: 2189: 2144: 2097: 2052: 2002: 1959: 1912: 1863: 1816: 1779: 1771: 1722: 1681: 1635: 1591: 1583: 1468: 1460: 1398: 1332: 1322: 1244: 1232:, Von Recklinghausen disease (referred to as "The Condition") is a key element of the plot. 1229: 1064: 693: 657: 324: 2773: 293:

Depression and social anxiety may occur as a result of disabilities caused by the condition

17: 5632: 5599: 5526: 5237: 5093: 4862: 4706: 4436: 4320: 4100: 4060: 3932: 3729: 1114: 974: 966: 939: 860: 845: 583: 215: 203: 184: 121: 3309: 2881: 2839: 1852:"A clinical study of neurofibromatosis-1 at a tertiary health care centre in south India" 3435:"FDA Approves First Therapy for Children with Debilitating and Disfiguring Rare Disease" 2810: 1146:

A first degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.

358:

can lead to scalloping of the posterior vertebral bodies and to the formation of cystic

254: 30:

For Von Recklinghausen's disease of bone, a disorder seen with hyperparathyroidism, see

5754: 5612: 5540: 4831: 4822: 4752: 4421: 4166: 4065: 3837: 3621: 3203: 3178: 3113: 3088: 3029: 3004: 2750: 2723: 2699: 2672: 2560: 2525: 2500: 2465: 2330: 2297: 2006: 1963: 1916: 1784: 1759: 1758:

Sullivan K, El-Hoss J, Quinlan KG, Deo N, Garton F, Seto JT, et al. (March 2014).

1686: 1669: 1596: 1571: 1473: 1448: 1337: 1310: 1240: 1236: 1213: 1140: 970: 516: 448: 425: 3526:"Neurofibromatosis Type 1: Persisting Misidentification of the "Elephant Man" Disease" 3065: 5825: 4940: 4826: 4742: 4110: 4075: 3419: 2968: 2630:

Matsui I, Tanimura M, Kobayashi N, Sawada T, Nagahara N, Akatsuka J (November 1993).

2450: 2395: 2356:"The importance of suicide risk assessment in patients affected by neurofibromatosis" 2149: 2132: 2131:

van der Vaart T, van Woerden GM, Elgersma Y, de Zeeuw CI, Schonewille M (June 2011).

1622:

Mutua V, Mong'are N, Bundi B, von Csefalvay C, Oriko D, Kitunguu P (September 2021).

1013: 992: 978: 962: 926: 824: 807: 605: 317: 313: 168: 129: 93: 2938: 2868:

Goldberg NS, Collins FS (November 1991). "The hunt for the neurofibromatosis gene".

2209: 2166: 2117: 2074: 2039:

Garg S, Lehtonen A, Huson SM, Emsley R, Trump D, Evans DG, Green J (February 2013).

2022: 1979: 1836: 1744: 1418: 5207: 4977: 4965: 4694: 4637: 4375: 4367: 3689: 1500:"Neurofibromatosis 1: Current Issues in Diagnosis, Therapy, and Patient Management" 1133: 697: 619: 601: 530: 526: 512: 495: 491: 349: 345: 164: 85: 2371: 1938: 3643: 3542: 2722:

Suarez-Kelly LP, Yu L, Kline D, Schneider EB, Agnese DM, Carson WE (2019-03-25).

2193: 1668:

Summers MA, Quinlan KG, Payne JM, Little DG, North KN, Schindeler A (June 2015).

1640: 5583: 5391: 4836: 4798: 4664: 4632: 4584: 4518: 3942: 3917: 3912: 3877: 3704: 3698: 3692: 3673: 1933: 1311:"Neurofibromatosis 1 Diagnosed in Mother Only after a Follow-up of Her Daughter" 1173: 1169: 769: 609: 359: 296:

Neurofibromas may, in 8-13% of cases, transition into cancer, which can be fatal

218:, another syndrome with vaguely similar symptoms, including cafe-au-lait spots. 89: 3243:"British couple successfully screens out genetic disorder using NHS-funded PGD" 2649:

10.1002/1097-0142(19931101)72:9<2746::AID-CNCR2820720936>3.0.CO;2-W

2542: 1464: 1402: 144:

disorder, which means that mutation or deletion of one copy (or allele) of the

5701: 4981: 4894: 4737: 3957: 3907: 3709: 3695: 3654: 3601: 3366: 3349: 2740: 2526:"Delineating the autistic phenotype in children with neurofibromatosis type 1" 1118: 813: 702: 643: 564: 3551: 2551: 2491: 2434: 2379: 2321: 2133:"Motor deficits in neurofibromatosis type 1 mice: the role of the cerebellum" 1868: 1851: 1649: 5687: 5147: 4656: 4604: 4398: 3952: 3684: 2905:"NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype" 2842: 2818: 2411:"Prevalence of Psychiatric Comorbidities in Patients With Neurofibromatosis" 2355: 2274: 753:. Due to cerebral tumors, cortical malformation, mesial temporal sclerosis. 405: 366: 339: 207: 176: 136:

causes tumors along the nervous system which can grow anywhere on the body.

3559: 3459:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf

3411: 3375: 3250: 3212: 3194: 3163: 3154: 3137: 3122: 3073: 3038: 3020: 2930: 2759: 2708: 2689: 2616: 2569: 2509: 2442: 2387: 2339: 2282: 2244: 2201: 2158: 2109: 2066: 2014: 1971: 1828: 1793: 1736: 1695: 1605: 1482: 1410: 1346: 1327: 424:

Bowing of a long bone with a tendency to fracture and not heal, yielding a

348:

and formation of cystic diverticula of the dura of the spine, unrelated to

331:

In NF-1, there can be a generalized abnormality of the soft tissues in the

3179:"Tumor microenvironment and neurofibromatosis type I: connecting the GAPs" 2986: 2889: 2826: 2657: 2609:

10.1002/(sici)1096-8628(19990326)89:1<31::aid-ajmg7>3.0.co;2-w

2237:

10.1002/(sici)1096-8628(19990326)89:1<38::aid-ajmg8>3.0.co;2-m

1570:

Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A (May 2002).

1432: 4886: 4729: 4007: 3947: 3525: 3104: 2977: 2426: 2101: 1775: 1587: 1048: 981: 954: 728: 637: 370: 336: 192: 3584: 563:

Motor deficits are common. Motor deficits due to NF-1 are probably not

557:

has been shown to be present in approximately 40% of children with NF-1.

5748: 5740: 5734: 5667: 5452: 2921: 2904: 2482: 2057: 2040: 1727: 1710: 1068: 477: 3403: 2313: 1923:. New York, NY: The National Neurofibromatosis Foundation, Inc. Print. 1820: 856:

30 - 50% of people with NF1 also meet the diagnostic criteria for ADHD

612:. Neurofibromas may arise sporadically, or in association with NF-1. 5776: 5762: 5681: 5626: 5387: 5332: 4814: 4647: 3752: 3596: 2256: 2254: 988: 880: 795: 548: 481: 120:, is a complex multi-system human disorder caused by the mutation of 1884:"Northwestern Health Sciences University ~ Diagnosis and Discussion" 969:(not to be confused with the disorder itself) which plays a role in 925:

Biological females with NF also have a five-fold increased risk of

887:

resulting from malignant degeneration of a plexiform neurofibroma.

5494: 5480: 5466: 5423: 5318: 5281: 5267: 5253: 3350:"Neurofibromatoses: part 1 - diagnosis and differential diagnosis" 3087:

Hannan F, Ho I, Tong JJ, Zhu Y, Nurnberg P, Zhong Y (April 2006).

1760:"NF1 is a critical regulator of muscle development and metabolism" 1572:"Malignant peripheral nerve sheath tumours in neurofibromatosis 1" 1122: 1034: 1024: 668: 485: 419:

List of radiographic findings associated with cutaneous conditions

332: 309: 264: 253: 1187:

In an open-label, phase 2 trial of selumetinib with 50 children:

1110:

Two or more neurofibromas of any type or 1 plexiform neurofibroma

790:

examination of the brain. These UBOs are typically found in the

163:

include brownish-red spots in the colored part of the eye called

5790: 5695: 5554: 5548: 5346: 5298: 5231: 5217: 3632: 3605: 3498:"Neurofibromatosis Type 1 (NF1) a Guide for Adults and Families" 3229: 1670:"Skeletal muscle and motor deficits in Neurofibromatosis Type 1" 1067:

may be used to identify the existence of NF-1 in the fetus. For

1043:

fashion, although it can also arise due to spontaneous mutation.

958: 669: 125: 5038: 4522: 4340: 4336: 3725: 5010:

WHO classification of the tumors of the central nervous system

1361:"About Neurofibromatosis – The University of Chicago Medicine" 278:

Congenital musculoskeletal disorders may or may not be present

5832:

Deficiencies of intracellular signaling peptides and proteins

5065:

Deficiencies of intracellular signaling peptides and proteins

428:. The most common bone to be affected is the tibia, causing 3496:

Ashton R, Crawford H, Morrison P, McKee S, Huson S (2012).

3325:

The neurofibromatoses: a pathogenetic and clinical overview

1711:"Muscle weakness in children with neurofibromatosis type 1" 678:

Chronic pain, numbness, and/or paralysis due to peripheral

1488:- "User License: Creative Commons Attribution (CC BY 4.0)" 961:

located on chromosomal segment 17q11.2 on the long arm of

3721: 759:. Drug therapy (57% amenable) where not resistant (29%). 547:

Approximately 42% of children with NF-1 have symptoms of

3848:

Pervasive developmental disorder not otherwise specified

2854:"Human Gene NF1 (uc002hgf.1) Description and Page Index" 2360:

International Journal of Psychiatry in Clinical Practice

1921:

Living with Neurofibromatosis Type 1: A Guide for Adults

1051:. The incidence of NF-1 is about 1 in 3500 live births. 737:. Epileptic seizures have been reported in up to 7% of 462:

List of conditions associated with café au lait macules

1709:

Cornett KM, North KN, Rose KJ, Burns J (August 2015).

1674:

Journal of Musculoskeletal & Neuronal Interactions

502:

or by removal by a plastic surgeon specialized in NF1.

615:

Neurofibroma conditions are progressive and include:

342:, resulting in maldevelopment of skeletal structures. 287:

Learning disabilities may arise in preschool children

281:

Cutaneous conditions may be observed in early infancy

3574: 3530:

The Journal of the American Board of Family Medicine

812:

Within the CNS, NF-1 manifests as a weakness of the

5712: 5657: 5571: 5440: 5399: 5385: 5367: 5206: 5155: 5146: 5107: 5079: 5070: 5002: 4930: 4908: 4885: 4855: 4811: 4781: 4751: 4728: 4705: 4655: 4646: 4626: 4617: 4593: 4565: 4556: 4480: 4457: 4397: 4374: 4313: 4287: 4261: 4230: 4185: 4139: 4036: 3971: 3868: 3825: 3759: 3664: 3578: 378:

Skeletal muscle weakness and motor control deficits

225:occur as the person ages and has hormonal changes. 99: 79: 47: 42: 1663: 1661: 1659: 2998: 2996: 2950: 2948: 2863: 2861: 2595:Korf BR (March 1999). "Plexiform neurofibromas". 1309:Kunc V, Venkatramani H, Sabapathy SR (May 2019). 1536:"Current Therapies for Neurofibromatosis Type 1" 2632:"Neurofibromatosis type 1 and childhood cancer" 386:Clinical findings in people with NF-1 include: 1617: 1615: 206:, a gene that is involved in the RAS pathway ( 5812:intracellular signaling peptides and proteins 5050: 4534: 4352: 3737: 2034: 2032: 8: 2415:The Primary Care Companion for CNS Disorders 2090:American Journal of Medical Genetics. Part A 1304: 1302: 171:, and larger benign tumors of nerves called 4873:Embryonal tumour with multilayered rosettes 3296:"Neurofibromatosis: Conference Statement". 3005:"Mouse models of neurofibromatosis 1 and 2" 1262:Characteristics of syndromic ASD conditions 198:NF-1 is a developmental syndrome caused by 5396: 5152: 5076: 5057: 5043: 5035: 4652: 4643: 4623: 4562: 4541: 4527: 4519: 4359: 4345: 4337: 4279:Ritvo Autism and Asperger Diagnostic Scale 3744: 3730: 3722: 3575: 2045:Developmental Medicine and Child Neurology 1715:Developmental Medicine and Child Neurology 1628:Medicine: Case Reports and Study Protocols 1060:Prenatal testing and prenatal expectations 467:Flat pigmented lesions of the skin called 75:Main symptoms of neurofibromatosis type I. 66: 39: 5674:EDARADD Hypohidrotic ectodermal dysplasia 3981:Avoidant/restrictive food intake disorder 3541: 3433:Office of the Commissioner (2020-04-10). 3365: 3202: 3153: 3112: 3028: 2976: 2920: 2749: 2739: 2698: 2688: 2647: 2559: 2541: 2499: 2481: 2329: 2148: 2056: 1867: 1783: 1726: 1685: 1639: 1595: 1472: 1336: 1326: 844:Children and adults with NF-1 often have 3986:Attention deficit hyperactivity disorder 1433:"NF1 | Children's Tumor Foundation" 1397:(8): 622–626, discussion 626–9, 626–51. 910:. Surgery (primary), radiation therapy. 555:Attention deficit hyperactivity disorder 5842:Neuro-cardio-facial-cutaneous syndromes 4994:Malignant peripheral nerve sheath tumor 4918:Primary central nervous system lymphoma 4842:Dysembryoplastic neuroepithelial tumour 4162:Multiple complex developmental disorder 3327:. London: Chapman & Hall. 1.3.2:9. 3230:NEUROFIBROMATOSIS, TYPE I; NF1 - 162200 1292:- Image by Mikael Häggström, MD, using 1273: 885:malignant peripheral nerve sheath tumor 4243:Autism Diagnostic Observation Schedule 2728:Hereditary Cancer in Clinical Practice 2470:Neuropsychiatric Disease and Treatment 859:11 - 26% of people with NF1 also have 538:Neurobehavioral developmental disorder 447:there is an orthopedic surgery called 430:congenital pseudarthrosis of the tibia 320:and associated neurologic impairment. 2774:"Cancer Statistics Review, 1975-2012" 2581: 2579: 148:is sufficient for the development of 7: 5305:Neutrophil immunodeficiency syndrome 5188:Albright's hereditary osteodystrophy 4508:Encephalocraniocutaneous lipomatosis 3310:10.1001/archneur.1988.00520290115023 2882:10.1001/archderm.1991.01680100105014 2597:American Journal of Medical Genetics 2225:American Journal of Medical Genetics 1031:Inheritance and spontaneous mutation 977:gene is a negative regulator of the 5659:Signal transducing adaptor proteins 4680:Subependymal giant cell astrocytoma 4003:Developmental coordination disorder 3478:. U.S. National Library of Medicine 3241:Blackburn-Starzan A (9 June 2008). 3226:Online Mendelian Inheritance in Man 3142:The Journal of Biological Chemistry 1025:collapsin response mediator protein 231:Friedrich Daniel von Recklinghausen 5243:KRAS Cardiofaciocutaneous syndrome 5134:X-linked intellectual disability 1 5129:Juvenile primary lateral sclerosis 2007:10.1212/01.WNL.0000055090.78351.C1 1964:10.1212/01.wnl.0000179303.72345.ce 1543:Mountain States Genetic Foundation 1507:Mountain States Genetic Foundation 608:, other perineural cell lines, or 355: 25: 5590:Bannayan–Riley–Ruvalcaba syndrome 4442:Bannayan–Riley–Ruvalcaba syndrome 4253:Gilliam Asperger's disorder scale 4081:Fetal valproate spectrum disorder 3853:Childhood disintegrative disorder 3003:Gutmann DH, Giovannini M (2002). 2677:Orphanet Journal of Rare Diseases 1315:Indian Journal of Plastic Surgery 1077:preimplantation genetic diagnosis 965:which encodes a protein known as 51: 27:Type of neurofibromatosis disease 5178:Progressive osseous heteroplasia 4868:Atypical teratoid rhabdoid tumor 3833:Pervasive developmental disorder 2150:10.1111/j.1601-183X.2011.00685.x 1294:source images by various authors 214:was in some cases confused with 187:, mental disabilities, multiple 5783:PRKCSH Polycystic liver disease 4488:Abdallat–Davis–Farrage syndrome 3472:"KOSELUGO- selumetinib capsule" 5769:Wolff–Parkinson–White syndrome 5173:Pseudopseudohypoparathyroidism 5072:GTP-binding protein regulators 4962:Cranial and paraspinal nerves 4274:Childhood Autism Spectrum Test 3177:Le LQ, Parada LF (July 2007). 1235:For many years it was thought 718:Central nervous system disease 1: 5377:Cardiofaciocutaneous syndrome 5325:Chylomicron retention disease 4675:Pleomorphic xanthoastrocytoma 4550:Tumours of the nervous system 4248:Childhood Autism Rating Scale 4106:PTEN hamartoma tumor syndrome 3996:obsessive–compulsive disorder 3928:Pathological demand avoidance 3812:Societal and cultural aspects 3354:Arquivos de Neuro-Psiquiatria 3066:10.1016/S0090-3019(97)00356-X 2778:SEER Cancer Statistics Review 2372:10.1080/13651501.2021.1921217 306:Musculoskeletal abnormalities 5619:X-linked myotubular myopathy 4720:Anaplastic oligodendroglioma 3543:10.3122/jabfm.2011.01.100219 3392:Pediatric Blood & Cancer 3323:Huson SM, Hughes RA (1994). 2969:10.1016/0888-7543(91)90017-9 2194:10.1177/08830738030180050501 1641:10.1097/MD9.0000000000000165 1280:- Source for main symptoms: 390:Reduced skeletal muscle size 167:, benign skin tumors called 5416:X-linked agammaglobulinemia 5260:Charcot–Marie–Tooth disease 4427:Multiple hamartoma syndrome 4238:Autism Diagnostic Interview 4018:Sensory processing disorder 3883:Autism and LGBTQ identities 1576:Journal of Medical Genetics 1136:(pigmented iris hamartomas) 987:pathway. It stimulates the 782:Focally degenerative myelin 409:mechanisms remain unknown. 118:von Recklinghausen syndrome 18:Segmental neurofibromatosis 5868: 5119:Marinesco–Sjögren syndrome 4126:Tuberous sclerosis complex 4116:Smith–Lemli–Opitz syndrome 4091:MECP2 duplication syndrome 4071:Cornelia de Lange syndrome 4023:Global developmental delay 2543:10.1186/s13229-021-00481-3 2182:Journal of Child Neurology 1465:10.1038/s41436-021-01170-5 1403:10.1177/088307380201700813 1391:Journal of Child Neurology 1247:, a much rarer condition. 937: 805: 788:magnetic resonance imaging 778:and associated blindness. 767: 726: 692:Renal artery anomalies or 459: 416: 335:, which is referred to as 179:(curvature of the spine), 53:von Recklinghausen disease 29: 5807: 5727:Neurofibromatosis type II 5561:Pseudohypoaldosteronism 2 5288:Griscelli syndrome type 2 5081:GTPase-activating protein 5018: 4389:Von Hippel–Lindau disease 4195:Facilitated communication 4046:22q11.2 deletion syndrome 3461:. Accessed June 21, 2020. 3367:10.1590/0004-282X20130241 3273:"About Neurofibromatosis" 2741:10.1186/s13053-019-0110-z 2137:Genes, Brain and Behavior 1445:Graphical abstract from: 1257:Neurofibromatosis type II 883:can arise in the form of 404:NF-1 is a disease in the 393:Reduced exercise capacity 74: 65: 5595:Lhermitte–Duclos disease 5193:McCune–Albright syndrome 5183:Pseudohypoparathyroidism 5089:Neurofibromatosis type I 4847:Lhermitte–Duclos disease 4771:Choroid plexus carcinoma 4766:Choroid plexus papilloma 4447:Lhermitte–Duclos disease 4269:Autism-spectrum quotient 4096:Neurofibromatosis type I 3093:Human Molecular Genetics 1934:MedlinePlus Encyclopedia 1869:10.4103/2349-5847.196302 1764:Human Molecular Genetics 1545:. Denver. Archived from 1509:. Denver. Archived from 1172:, is a drug produced by 1039:NF-1 is inherited in an 861:Autism Spectrum Disorder 653:Nerve root neurofibroma. 323:Disorders affecting the 301:Musculoskeletal disorder 110:Neurofibromatosis type I 43:Neurofibromatosis type 1 32:osteitis fibrosa cystica 5353:Bardet–Biedl syndrome 3 4416:Pallister–Hall syndrome 4200:Lancet MMR autism fraud 4152:Critical autism studies 4051:22q13 deletion syndrome 4013:Intellectual disability 3963:Emotional dysregulation 3860:High-functioning autism 2870:Archives of Dermatology 2819:10.1126/science.2134734 696:and associated chronic 640:enlargement of a nerve. 274:is roughly as follows: 173:plexiform neurofibromas 5837:Neurological disorders 5501:Peutz–Jeghers syndrome 5487:Incontinentia pigmenti 5473:Li–Fraumeni syndrome 2 5124:Aarskog–Scott syndrome 4690:Anaplastic astrocytoma 4685:Fibrillary astrocytoma 4503:Peutz–Jeghers syndrome 4498:Incontinentia pigmenti 4412:Hypothalamic hamartoma 4210:Rapid prompting method 4157:Double empathy problem 4147:Autism rights movement 3304:(5): 575. 1 May 1988. 3195:10.1038/sj.onc.1210261 3155:10.1074/jbc.M503707200 3021:10.1038/sj.neo.7900249 2690:10.1186/1750-1172-6-18 1328:10.1055/s-0039-1693503 1182:gastrointestinal tract 1073:in vitro fertilisation 1044: 951:microdeletion syndrome 674: 620:Plexiform neurofibroma 578:Nervous system disease 438:limb-sparing technique 413:Facial bones and limbs 316:dysplasia, congenital 270: 262: 5605:Proteus-like syndrome 5459:Coffin-Lowry syndrome 4946:Esthesioneuroblastoma 4670:Pilocytic astrocytoma 4493:Ataxia telangiectasia 4384:Sturge–Weber syndrome 4295:Autism-related topics 3869:Associated conditions 3298:Archives of Neurology 2275:10.1093/neuros/nyz244 1856:Pigment International 1226:The Covenant of Water 1206:variable expressivity 1075:, it is possible via 1038: 672: 626:Solitary neurofibroma 591:Peripheral neuropathy 268: 261:characteristic of NF1 257: 181:learning disabilities 56:morbus Recklinghausen 5513:Myotonic dystrophy 1 4951:Ganglioneuroblastoma 4856:CNS embryonal tumors 4761:Choroid plexus tumor 4300:Fictional characters 4038:Associated syndromes 2427:10.4088/PCC.23m03514 2102:10.1002/ajmg.a.33235 1588:10.1136/jmg.39.5.311 1498:Viskochil D (2010). 1453:Genetics in Medicine 1087:spontaneous mutation 1079:to screen for NF-1. 1049:spontaneous mutation 1023:, and a second with 945:Neurofibromin 1 gene 4794:Gliomatosis cerebri 4177:Violence and autism 3973:Comorbid conditions 3710:Neurofibromatosis 1 3148:(47): 39524–39533. 2811:1990Sci...249..181W 1365:www.uchospitals.edu 1283:"Neurofibromatosis" 985:signal transduction 776:optic nerve gliomas 687:Other complications 630:computed tomography 523:Optic nerve gliomas 492:Dermal neurofibroma 5643:Metachondromatosis 5339:Joubert syndrome 8 5274:Carpenter syndrome 5109:Guanine nucleotide 5099:Tuberous sclerosis 4958:Nerve sheath tumor 4900:Hemangiopericytoma 4407:Tuberous sclerosis 4086:Fragile X syndrome 3893:Autistic catatonia 3665:External resources 3105:10.1093/hmg/ddl023 3054:Surgical Neurology 2922:10.1002/humu.21271 2915:(6): E1506–E1518. 2483:10.2147/NDT.S75038 2058:10.1111/dmcn.12043 1809:Muscle & Nerve 1776:10.1093/hmg/ddt515 1728:10.1111/dmcn.12777 1220:In popular culture 1128:Optic nerve glioma 1104:café-au-lait spots 1093:Post-natal testing 1045: 1041:autosomal dominant 867:Puberty and height 710:Optic nerve glioma 707:Plexiform fibromas 680:nerve sheath tumor 675: 665:Nerve sheath tumor 634:magnetic resonance 525:along one or both 354:Radiographically, 271: 263: 250:Signs and symptoms 200:germline mutations 142:autosomal dominant 5819: 5818: 5653: 5652: 5633:Noonan syndrome 1 5527:Seckel syndrome 1 5363: 5362: 5238:Noonan syndrome 3 5224:Costello syndrome 5142: 5141: 5032: 5031: 4971:Neurofibromatosis 4926: 4925: 4881: 4880: 4807: 4806: 4715:Oligodendroglioma 4613: 4612: 4580:Craniopharyngioma 4516: 4515: 4459:Neurofibromatosis 4334: 4333: 4231:Diagnostic scales 4131:Williams syndrome 4056:Angelman syndrome 3938:Special interests 3903:Autistic meltdown 3843:Asperger syndrome 3719: 3718: 3404:10.1002/pbc.29633 3334:978-0-412-38920-7 3253:on March 30, 2016 3189:(32): 4609–4616. 2876:(11): 1705–1707. 2840:"neurofibromin 1" 2805:(4965): 181–186. 2314:10.1111/cge.12551 2302:Clinical Genetics 1911:Piersall, Linda, 1821:10.1002/mus.23324 1534:Klesse L (2010). 1113:Freckling in the 792:Cerebral peduncle 259:Café au lait spot 107: 106: 37:Medical condition 16:(Redirected from 5859: 5852:Syndromic autism 5638:LEOPARD syndrome 5541:Oguchi disease 2 5442:Serine/threonine 5430:ZAP70 deficiency 5397: 5153: 5077: 5059: 5052: 5045: 5036: 5023:brain metastasis 4987:Acoustic neuroma 4789:Oligoastrocytoma 4782:Multiple/unknown 4653: 4644: 4624: 4598: 4573: 4563: 4543: 4536: 4529: 4520: 4432:Proteus syndrome 4361: 4354: 4347: 4338: 4326:Sensory friendly 4262:Screening scales 4121:Timothy syndrome 4028:Verbal Dyspraxia 3991:Anxiety disorder 3923:Nonverbal autism 3898:Autistic masking 3888:Autistic burnout 3746: 3739: 3732: 3723: 3576: 3564: 3563: 3545: 3521: 3515: 3514: 3512: 3511: 3505:Nerve Tumours UK 3502: 3493: 3487: 3486: 3484: 3483: 3468: 3462: 3455: 3449: 3448: 3446: 3445: 3430: 3424: 3423: 3386: 3380: 3379: 3369: 3345: 3339: 3338: 3320: 3314: 3313: 3293: 3287: 3286: 3284: 3283: 3269: 3263: 3262: 3260: 3258: 3249:. Archived from 3238: 3232: 3223: 3217: 3216: 3206: 3174: 3168: 3167: 3157: 3133: 3127: 3126: 3116: 3099:(7): 1087–1098. 3084: 3078: 3077: 3049: 3043: 3042: 3032: 3000: 2991: 2990: 2980: 2952: 2943: 2942: 2924: 2900: 2894: 2893: 2865: 2856: 2851: 2845: 2837: 2831: 2830: 2794: 2788: 2787: 2785: 2784: 2770: 2764: 2763: 2753: 2743: 2719: 2713: 2712: 2702: 2692: 2668: 2662: 2661: 2651: 2642:(9): 2746–2754. 2627: 2621: 2620: 2592: 2586: 2583: 2574: 2573: 2563: 2545: 2530:Molecular Autism 2520: 2514: 2513: 2503: 2485: 2461: 2455: 2454: 2406: 2400: 2399: 2350: 2344: 2343: 2333: 2293: 2287: 2286: 2258: 2249: 2248: 2220: 2214: 2213: 2177: 2171: 2170: 2152: 2128: 2122: 2121: 2085: 2079: 2078: 2060: 2036: 2027: 2026: 2001:(7): 1139–1145. 1990: 1984: 1983: 1958:(7): 1037–1044. 1947: 1941: 1930: 1924: 1913:David H. Gutmann 1909: 1903: 1902: 1900: 1899: 1890:. Archived from 1888:www.nwhealth.edu 1880: 1874: 1873: 1871: 1847: 1841: 1840: 1804: 1798: 1797: 1787: 1770:(5): 1250–1259. 1755: 1749: 1748: 1730: 1706: 1700: 1699: 1689: 1665: 1654: 1653: 1643: 1619: 1610: 1609: 1599: 1567: 1561: 1560: 1558: 1557: 1551: 1540: 1531: 1525: 1524: 1522: 1521: 1515: 1504: 1495: 1489: 1486: 1476: 1459:(8): 1506–1513. 1443: 1437: 1436: 1429: 1423: 1422: 1386: 1380: 1379: 1377: 1376: 1367:. Archived from 1357: 1351: 1350: 1340: 1330: 1306: 1297: 1290: 1278: 1245:Proteus syndrome 1239:, known as the 1230:Abraham Verghese 1123:inguinal regions 1065:Prenatal testing 1021:adenylyl cyclase 740: 694:pheochromocytoma 486:inguinal regions 244: 240: 228: 224: 213: 185:vision disorders 162: 155: 151: 147: 139: 135: 70: 40: 21: 5867: 5866: 5862: 5861: 5860: 5858: 5857: 5856: 5822: 5821: 5820: 5815: 5803: 5708: 5649: 5600:Cowden syndrome 5574: 5567: 5443: 5436: 5401:Tyrosine kinase 5381: 5359: 5202: 5138: 5111:exchange factor 5110: 5103: 5094:Watson syndrome 5066: 5063: 5033: 5028: 5027: 5014: 4998: 4922: 4904: 4877: 4863:Medulloblastoma 4851: 4813: 4803: 4777: 4747: 4724: 4707:Oligodendrocyte 4701: 4636: 4630: 4628:Neuroepithelial 4609: 4594: 4589: 4566: 4552: 4547: 4517: 4512: 4476: 4453: 4437:Cowden syndrome 4393: 4370: 4365: 4335: 4330: 4321:Autism-friendly 4309: 4283: 4257: 4226: 4181: 4135: 4101:Noonan syndrome 4061:CHARGE syndrome 4032: 3967: 3933:Savant syndrome 3870: 3864: 3821: 3802:Pathophysiology 3755: 3750: 3720: 3715: 3714: 3660: 3659: 3587: 3573: 3568: 3567: 3523: 3522: 3518: 3509: 3507: 3500: 3495: 3494: 3490: 3481: 3479: 3470: 3469: 3465: 3456: 3452: 3443: 3441: 3432: 3431: 3427: 3388: 3387: 3383: 3347: 3346: 3342: 3335: 3322: 3321: 3317: 3295: 3294: 3290: 3281: 3279: 3271: 3270: 3266: 3256: 3254: 3240: 3239: 3235: 3224: 3220: 3176: 3175: 3171: 3135: 3134: 3130: 3086: 3085: 3081: 3051: 3050: 3046: 3002: 3001: 2994: 2954: 2953: 2946: 2902: 2901: 2897: 2867: 2866: 2859: 2852: 2848: 2838: 2834: 2796: 2795: 2791: 2782: 2780: 2772: 2771: 2767: 2721: 2720: 2716: 2670: 2669: 2665: 2629: 2628: 2624: 2594: 2593: 2589: 2584: 2577: 2522: 2521: 2517: 2463: 2462: 2458: 2408: 2407: 2403: 2352: 2351: 2347: 2295: 2294: 2290: 2260: 2259: 2252: 2222: 2221: 2217: 2179: 2178: 2174: 2130: 2129: 2125: 2087: 2086: 2082: 2038: 2037: 2030: 1992: 1991: 1987: 1949: 1948: 1944: 1931: 1927: 1910: 1906: 1897: 1895: 1882: 1881: 1877: 1849: 1848: 1844: 1806: 1805: 1801: 1757: 1756: 1752: 1708: 1707: 1703: 1667: 1666: 1657: 1621: 1620: 1613: 1569: 1568: 1564: 1555: 1553: 1549: 1538: 1533: 1532: 1528: 1519: 1517: 1513: 1502: 1497: 1496: 1492: 1487: 1446: 1444: 1440: 1431: 1430: 1426: 1388: 1387: 1383: 1374: 1372: 1359: 1358: 1354: 1308: 1307: 1300: 1291: 1281: 1279: 1275: 1270: 1253: 1222: 1201: 1167: 1162: 1153: 1095: 1062: 1057: 1033: 1005: 975:Neurofibromin 1 947: 942: 940:Neurofibromin 1 936: 923: 878: 869: 842: 840:Neurodivergence 833: 810: 804: 784: 772: 766: 738: 731: 725: 720: 689: 667: 598: 593: 584:Schwannomatosis 580: 540: 509: 499: 464: 458: 434:Ilizarov method 421: 415: 303: 252: 242: 238: 226: 222: 216:Legius syndrome 211: 160: 153: 149: 145: 137: 133: 122:neurofibromin 1 38: 35: 28: 23: 22: 15: 12: 11: 5: 5865: 5863: 5855: 5854: 5849: 5844: 5839: 5834: 5824: 5823: 5817: 5816: 5808: 5805: 5804: 5802: 5801: 5800: 5799: 5787: 5786: 5785: 5773: 5772: 5771: 5759: 5758: 5757: 5755:Carney complex 5745: 5744: 5743: 5731: 5730: 5729: 5716: 5714: 5710: 5709: 5707: 5706: 5705: 5704: 5692: 5691: 5690: 5678: 5677: 5676: 5663: 5661: 5655: 5654: 5651: 5650: 5648: 5647: 5646: 5645: 5640: 5635: 5623: 5622: 5621: 5609: 5608: 5607: 5602: 5597: 5592: 5579: 5577: 5569: 5568: 5566: 5565: 5564: 5563: 5545: 5544: 5543: 5531: 5530: 5529: 5517: 5516: 5515: 5505: 5504: 5503: 5491: 5490: 5489: 5477: 5476: 5475: 5463: 5462: 5461: 5448: 5446: 5438: 5437: 5435: 5434: 5433: 5432: 5420: 5419: 5418: 5405: 5403: 5394: 5383: 5382: 5380: 5379: 5373: 5371: 5365: 5364: 5361: 5360: 5358: 5357: 5356: 5355: 5343: 5342: 5341: 5329: 5328: 5327: 5310: 5309: 5308: 5307: 5293: 5292: 5291: 5290: 5278: 5277: 5276: 5264: 5263: 5262: 5248: 5247: 5246: 5245: 5240: 5228: 5227: 5226: 5212: 5210: 5204: 5203: 5201: 5200: 5195: 5190: 5185: 5180: 5175: 5161: 5159: 5150: 5144: 5143: 5140: 5139: 5137: 5136: 5131: 5126: 5121: 5115: 5113: 5105: 5104: 5102: 5101: 5096: 5091: 5085: 5083: 5074: 5068: 5067: 5064: 5062: 5061: 5054: 5047: 5039: 5030: 5029: 5019: 5016: 5015: 5013: 5012: 5006: 5004: 5000: 4999: 4997: 4996: 4991: 4990: 4989: 4975: 4974: 4973: 4968: 4960: 4955: 4954: 4953: 4948: 4937: 4935: 4928: 4927: 4924: 4923: 4921: 4920: 4914: 4912: 4906: 4905: 4903: 4902: 4897: 4891: 4889: 4883: 4882: 4879: 4878: 4876: 4875: 4870: 4865: 4859: 4857: 4853: 4852: 4850: 4849: 4844: 4839: 4834: 4832:Retinoblastoma 4829: 4823:Ganglioneuroma 4819: 4817: 4809: 4808: 4805: 4804: 4802: 4801: 4796: 4791: 4785: 4783: 4779: 4778: 4776: 4775: 4774: 4773: 4768: 4757: 4755: 4753:Choroid plexus 4749: 4748: 4746: 4745: 4740: 4734: 4732: 4726: 4725: 4723: 4722: 4717: 4711: 4709: 4703: 4702: 4700: 4699: 4698: 4697: 4692: 4687: 4682: 4677: 4672: 4661: 4659: 4650: 4641: 4621: 4615: 4614: 4611: 4610: 4608: 4607: 4601: 4599: 4591: 4590: 4588: 4587: 4582: 4576: 4574: 4560: 4554: 4553: 4548: 4546: 4545: 4538: 4531: 4523: 4514: 4513: 4511: 4510: 4505: 4500: 4495: 4490: 4484: 4482: 4478: 4477: 4475: 4474: 4469: 4463: 4461: 4455: 4454: 4452: 4451: 4450: 4449: 4444: 4439: 4434: 4424: 4422:Megalencephaly 4419: 4409: 4403: 4401: 4395: 4394: 4392: 4391: 4386: 4380: 4378: 4372: 4371: 4366: 4364: 4363: 4356: 4349: 4341: 4332: 4331: 4329: 4328: 4323: 4317: 4315: 4314:Accommodations 4311: 4310: 4308: 4307: 4302: 4297: 4291: 4289: 4285: 4284: 4282: 4281: 4276: 4271: 4265: 4263: 4259: 4258: 4256: 4255: 4250: 4245: 4240: 4234: 4232: 4228: 4227: 4225: 4224: 4223: 4222: 4212: 4207: 4202: 4197: 4191: 4189: 4183: 4182: 4180: 4179: 4174: 4172:TEACCH program 4169: 4167:Neurodiversity 4164: 4159: 4154: 4149: 4143: 4141: 4140:Related issues 4137: 4136: 4134: 4133: 4128: 4123: 4118: 4113: 4108: 4103: 4098: 4093: 4088: 4083: 4078: 4073: 4068: 4066:Cohen syndrome 4063: 4058: 4053: 4048: 4042: 4040: 4034: 4033: 4031: 4030: 4025: 4020: 4015: 4010: 4005: 4000: 3999: 3998: 3988: 3983: 3977: 3975: 3969: 3968: 3966: 3965: 3960: 3955: 3950: 3945: 3940: 3935: 3930: 3925: 3920: 3915: 3910: 3905: 3900: 3895: 3890: 3885: 3880: 3874: 3872: 3866: 3865: 3863: 3862: 3857: 3856: 3855: 3850: 3845: 3840: 3838:Classic autism 3829: 3827: 3823: 3822: 3820: 3819: 3814: 3809: 3807:Sex and gender 3804: 3799: 3794: 3789: 3784: 3779: 3774: 3769: 3763: 3761: 3757: 3756: 3751: 3749: 3748: 3741: 3734: 3726: 3717: 3716: 3713: 3712: 3701: 3681: 3669: 3668: 3666: 3662: 3661: 3658: 3657: 3646: 3635: 3624: 3609: 3588: 3583: 3582: 3580: 3579:Classification 3572: 3571:External links 3569: 3566: 3565: 3536:(1): 112–114. 3516: 3488: 3463: 3450: 3425: 3381: 3360:(3): 241–250. 3340: 3333: 3315: 3288: 3264: 3233: 3218: 3169: 3128: 3079: 3060:(2): 211–218. 3044: 3015:(4): 279–290. 2992: 2963:(4): 931–940. 2944: 2909:Human Mutation 2895: 2857: 2846: 2832: 2789: 2765: 2714: 2663: 2622: 2587: 2575: 2515: 2456: 2401: 2366:(4): 350–355. 2345: 2308:(5): 425–430. 2288: 2269:(5): 646–655. 2250: 2215: 2188:(5): 338–342. 2172: 2143:(4): 404–409. 2123: 2096:(2): 284–290. 2080: 2051:(2): 139–145. 2028: 1985: 1942: 1925: 1917:Rosalie Ferner 1904: 1875: 1842: 1815:(3): 394–399. 1799: 1750: 1721:(8): 733–736. 1701: 1680:(2): 161–170. 1655: 1611: 1582:(5): 311–314. 1562: 1526: 1490: 1438: 1424: 1381: 1352: 1298: 1272: 1271: 1269: 1266: 1265: 1264: 1259: 1252: 1249: 1237:Joseph Merrick 1224:In the novel " 1221: 1218: 1200: 1197: 1196: 1195: 1192: 1166: 1163: 1161: 1160:Drug Therapies 1158: 1152: 1149: 1148: 1147: 1144: 1141:pseudarthrosis 1137: 1130: 1125: 1111: 1108: 1094: 1091: 1061: 1058: 1056: 1053: 1032: 1029: 1008:respectively. 1004: 1001: 971:cell signaling 946: 943: 938:Main article: 935: 932: 922: 919: 918: 917: 911: 905: 895: 877: 874: 868: 865: 864: 863: 857: 841: 838: 832: 829: 806:Main article: 803: 800: 783: 780: 768:Main article: 765: 762: 761: 760: 754: 748: 742: 727:Main article: 724: 721: 719: 716: 715: 714: 711: 708: 705: 700: 688: 685: 684: 683: 666: 663: 662: 661: 654: 651: 641: 623: 597: 594: 592: 589: 579: 576: 575: 574: 568: 561: 558: 552: 539: 536: 535: 534: 520: 508: 505: 504: 503: 497: 489: 475: 457: 454: 453: 452: 449:epiphysiodesis 444: 441: 426:pseudarthrosis 414: 411: 398: 397: 394: 391: 375: 374: 363: 352: 343: 308:affecting the 302: 299: 298: 297: 294: 291: 288: 285: 282: 279: 251: 248: 105: 104: 101: 97: 96: 83: 77: 76: 72: 71: 63: 62: 61: 60: 57: 54: 49: 45: 44: 36: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 5864: 5853: 5850: 5848: 5845: 5843: 5840: 5838: 5835: 5833: 5830: 5829: 5827: 5814: 5813: 5806: 5798: 5795: 5794: 5793: 5792: 5788: 5784: 5781: 5780: 5779: 5778: 5774: 5770: 5767: 5766: 5765: 5764: 5760: 5756: 5753: 5752: 5751: 5750: 5746: 5742: 5739: 5738: 5737: 5736: 5732: 5728: 5725: 5724: 5723: 5722: 5718: 5717: 5715: 5711: 5703: 5700: 5699: 5698: 5697: 5693: 5689: 5686: 5685: 5684: 5683: 5679: 5675: 5672: 5671: 5670: 5669: 5665: 5664: 5662: 5660: 5656: 5644: 5641: 5639: 5636: 5634: 5631: 5630: 5629: 5628: 5624: 5620: 5617: 5616: 5615: 5614: 5610: 5606: 5603: 5601: 5598: 5596: 5593: 5591: 5588: 5587: 5586: 5585: 5581: 5580: 5578: 5576: 5570: 5562: 5559: 5558: 5557: 5556: 5551: 5550: 5546: 5542: 5539: 5538: 5537: 5536: 5532: 5528: 5525: 5524: 5523: 5522: 5518: 5514: 5511: 5510: 5509: 5506: 5502: 5499: 5498: 5497: 5496: 5492: 5488: 5485: 5484: 5483: 5482: 5478: 5474: 5471: 5470: 5469: 5468: 5464: 5460: 5457: 5456: 5455: 5454: 5450: 5449: 5447: 5445: 5439: 5431: 5428: 5427: 5426: 5425: 5421: 5417: 5414: 5413: 5412: 5411: 5407: 5406: 5404: 5402: 5398: 5395: 5393: 5389: 5384: 5378: 5375: 5374: 5372: 5370: 5366: 5354: 5351: 5350: 5349: 5348: 5344: 5340: 5337: 5336: 5335: 5334: 5330: 5326: 5323: 5322: 5321: 5320: 5315: 5312: 5311: 5306: 5303: 5302: 5301: 5300: 5295: 5294: 5289: 5286: 5285: 5284: 5283: 5279: 5275: 5272: 5271: 5270: 5269: 5265: 5261: 5258: 5257: 5256: 5255: 5250: 5249: 5244: 5241: 5239: 5236: 5235: 5234: 5233: 5229: 5225: 5222: 5221: 5220: 5219: 5214: 5213: 5211: 5209: 5205: 5199: 5196: 5194: 5191: 5189: 5186: 5184: 5181: 5179: 5176: 5174: 5170: 5166: 5163: 5162: 5160: 5158: 5157:Heterotrimeic 5154: 5151: 5149: 5145: 5135: 5132: 5130: 5127: 5125: 5122: 5120: 5117: 5116: 5114: 5112: 5106: 5100: 5097: 5095: 5092: 5090: 5087: 5086: 5084: 5082: 5078: 5075: 5073: 5069: 5060: 5055: 5053: 5048: 5046: 5041: 5040: 5037: 5026: 5024: 5017: 5011: 5008: 5007: 5005: 5001: 4995: 4992: 4988: 4985: 4984: 4983: 4979: 4976: 4972: 4969: 4967: 4964: 4963: 4961: 4959: 4956: 4952: 4949: 4947: 4944: 4943: 4942: 4941:Neuroblastoma 4939: 4938: 4936: 4933: 4929: 4919: 4916: 4915: 4913: 4911: 4910:Hematopoietic 4907: 4901: 4898: 4896: 4893: 4892: 4890: 4888: 4884: 4874: 4871: 4869: 4866: 4864: 4861: 4860: 4858: 4854: 4848: 4845: 4843: 4840: 4838: 4835: 4833: 4830: 4828: 4827:Ganglioglioma 4824: 4821: 4820: 4818: 4816: 4810: 4800: 4797: 4795: 4792: 4790: 4787: 4786: 4784: 4780: 4772: 4769: 4767: 4764: 4763: 4762: 4759: 4758: 4756: 4754: 4750: 4744: 4743:Subependymoma 4741: 4739: 4736: 4735: 4733: 4731: 4727: 4721: 4718: 4716: 4713: 4712: 4710: 4708: 4704: 4696: 4693: 4691: 4688: 4686: 4683: 4681: 4678: 4676: 4673: 4671: 4668: 4667: 4666: 4663: 4662: 4660: 4658: 4654: 4651: 4649: 4645: 4642: 4639: 4638:spinal tumors 4634: 4629: 4625: 4622: 4620: 4616: 4606: 4603: 4602: 4600: 4597: 4592: 4586: 4583: 4581: 4578: 4577: 4575: 4572: 4570: 4564: 4561: 4559: 4555: 4551: 4544: 4539: 4537: 4532: 4530: 4525: 4524: 4521: 4509: 4506: 4504: 4501: 4499: 4496: 4494: 4491: 4489: 4486: 4485: 4483: 4479: 4473: 4470: 4468: 4465: 4464: 4462: 4460: 4456: 4448: 4445: 4443: 4440: 4438: 4435: 4433: 4430: 4429: 4428: 4425: 4423: 4420: 4417: 4413: 4410: 4408: 4405: 4404: 4402: 4400: 4396: 4390: 4387: 4385: 4382: 4381: 4379: 4377: 4373: 4369: 4362: 4357: 4355: 4350: 4348: 4343: 4342: 4339: 4327: 4324: 4322: 4319: 4318: 4316: 4312: 4306: 4303: 4301: 4298: 4296: 4293: 4292: 4290: 4286: 4280: 4277: 4275: 4272: 4270: 4267: 4266: 4264: 4260: 4254: 4251: 4249: 4246: 4244: 4241: 4239: 4236: 4235: 4233: 4229: 4221: 4218: 4217: 4216: 4213: 4211: 4208: 4206: 4203: 4201: 4198: 4196: 4193: 4192: 4190: 4188: 4187:Controversies 4184: 4178: 4175: 4173: 4170: 4168: 4165: 4163: 4160: 4158: 4155: 4153: 4150: 4148: 4145: 4144: 4142: 4138: 4132: 4129: 4127: 4124: 4122: 4119: 4117: 4114: 4112: 4111:Rett syndrome 4109: 4107: 4104: 4102: 4099: 4097: 4094: 4092: 4089: 4087: 4084: 4082: 4079: 4077: 4076:Down syndrome 4074: 4072: 4069: 4067: 4064: 4062: 4059: 4057: 4054: 4052: 4049: 4047: 4044: 4043: 4041: 4039: 4035: 4029: 4026: 4024: 4021: 4019: 4016: 4014: 4011: 4009: 4006: 4004: 4001: 3997: 3994: 3993: 3992: 3989: 3987: 3984: 3982: 3979: 3978: 3976: 3974: 3970: 3964: 3961: 3959: 3956: 3954: 3951: 3949: 3946: 3944: 3941: 3939: 3936: 3934: 3931: 3929: 3926: 3924: 3921: 3919: 3916: 3914: 3911: 3909: 3906: 3904: 3901: 3899: 3896: 3894: 3891: 3889: 3886: 3884: 3881: 3879: 3876: 3875: 3873: 3871:and phenomena 3867: 3861: 3858: 3854: 3851: 3849: 3846: 3844: 3841: 3839: 3836: 3835: 3834: 3831: 3830: 3828: 3824: 3818: 3815: 3813: 3810: 3808: 3805: 3803: 3800: 3798: 3795: 3793: 3790: 3788: 3785: 3783: 3780: 3778: 3775: 3773: 3770: 3768: 3765: 3764: 3762: 3758: 3754: 3747: 3742: 3740: 3735: 3733: 3728: 3727: 3724: 3711: 3707: 3706: 3702: 3700: 3697: 3694: 3691: 3687: 3686: 3682: 3680: 3676: 3675: 3671: 3670: 3667: 3663: 3656: 3652: 3651: 3647: 3645: 3641: 3640: 3636: 3634: 3630: 3629: 3625: 3623: 3619: 3618: 3614: 3610: 3607: 3603: 3599: 3598: 3594: 3590: 3589: 3586: 3581: 3577: 3570: 3561: 3557: 3553: 3549: 3544: 3539: 3535: 3531: 3527: 3520: 3517: 3506: 3499: 3492: 3489: 3477: 3473: 3467: 3464: 3460: 3454: 3451: 3440: 3436: 3429: 3426: 3421: 3417: 3413: 3409: 3405: 3401: 3398:(8): e29633. 3397: 3393: 3385: 3382: 3377: 3373: 3368: 3363: 3359: 3355: 3351: 3344: 3341: 3336: 3330: 3326: 3319: 3316: 3311: 3307: 3303: 3299: 3292: 3289: 3278: 3274: 3268: 3265: 3252: 3248: 3244: 3237: 3234: 3231: 3227: 3222: 3219: 3214: 3210: 3205: 3200: 3196: 3192: 3188: 3184: 3180: 3173: 3170: 3165: 3161: 3156: 3151: 3147: 3143: 3139: 3132: 3129: 3124: 3120: 3115: 3110: 3106: 3102: 3098: 3094: 3090: 3083: 3080: 3075: 3071: 3067: 3063: 3059: 3055: 3048: 3045: 3040: 3036: 3031: 3026: 3022: 3018: 3014: 3010: 3006: 2999: 2997: 2993: 2988: 2984: 2979: 2978:2027.42/29018 2974: 2970: 2966: 2962: 2958: 2951: 2949: 2945: 2940: 2936: 2932: 2928: 2923: 2918: 2914: 2910: 2906: 2899: 2896: 2891: 2887: 2883: 2879: 2875: 2871: 2864: 2862: 2858: 2855: 2850: 2847: 2844: 2841: 2836: 2833: 2828: 2824: 2820: 2816: 2812: 2808: 2804: 2800: 2793: 2790: 2779: 2775: 2769: 2766: 2761: 2757: 2752: 2747: 2742: 2737: 2733: 2729: 2725: 2718: 2715: 2710: 2706: 2701: 2696: 2691: 2686: 2682: 2678: 2674: 2667: 2664: 2659: 2655: 2650: 2645: 2641: 2637: 2633: 2626: 2623: 2618: 2614: 2610: 2606: 2602: 2598: 2591: 2588: 2582: 2580: 2576: 2571: 2567: 2562: 2557: 2553: 2549: 2544: 2539: 2535: 2531: 2527: 2519: 2516: 2511: 2507: 2502: 2497: 2493: 2489: 2484: 2479: 2475: 2471: 2467: 2460: 2457: 2452: 2448: 2444: 2440: 2436: 2432: 2428: 2424: 2420: 2416: 2412: 2405: 2402: 2397: 2393: 2389: 2385: 2381: 2377: 2373: 2369: 2365: 2361: 2357: 2349: 2346: 2341: 2337: 2332: 2327: 2323: 2319: 2315: 2311: 2307: 2303: 2299: 2292: 2289: 2284: 2280: 2276: 2272: 2268: 2264: 2257: 2255: 2251: 2246: 2242: 2238: 2234: 2230: 2226: 2219: 2216: 2211: 2207: 2203: 2199: 2195: 2191: 2187: 2183: 2176: 2173: 2168: 2164: 2160: 2156: 2151: 2146: 2142: 2138: 2134: 2127: 2124: 2119: 2115: 2111: 2107: 2103: 2099: 2095: 2091: 2084: 2081: 2076: 2072: 2068: 2064: 2059: 2054: 2050: 2046: 2042: 2035: 2033: 2029: 2024: 2020: 2016: 2012: 2008: 2004: 2000: 1996: 1989: 1986: 1981: 1977: 1973: 1969: 1965: 1961: 1957: 1953: 1946: 1943: 1940: 1936: 1935: 1929: 1926: 1922: 1918: 1914: 1908: 1905: 1894:on 2016-03-04 1893: 1889: 1885: 1879: 1876: 1870: 1865: 1861: 1857: 1853: 1846: 1843: 1838: 1834: 1830: 1826: 1822: 1818: 1814: 1810: 1803: 1800: 1795: 1791: 1786: 1781: 1777: 1773: 1769: 1765: 1761: 1754: 1751: 1746: 1742: 1738: 1734: 1729: 1724: 1720: 1716: 1712: 1705: 1702: 1697: 1693: 1688: 1683: 1679: 1675: 1671: 1664: 1662: 1660: 1656: 1651: 1647: 1642: 1637: 1633: 1629: 1625: 1618: 1616: 1612: 1607: 1603: 1598: 1593: 1589: 1585: 1581: 1577: 1573: 1566: 1563: 1552:on 2012-03-09 1548: 1544: 1537: 1530: 1527: 1516:on 2015-11-06 1512: 1508: 1501: 1494: 1491: 1484: 1480: 1475: 1470: 1466: 1462: 1458: 1454: 1450: 1442: 1439: 1434: 1428: 1425: 1420: 1416: 1412: 1408: 1404: 1400: 1396: 1392: 1385: 1382: 1371:on 2015-09-07 1370: 1366: 1362: 1356: 1353: 1348: 1344: 1339: 1334: 1329: 1324: 1320: 1316: 1312: 1305: 1303: 1299: 1295: 1289:. 2021-01-21. 1288: 1284: 1277: 1274: 1267: 1263: 1260: 1258: 1255: 1254: 1250: 1248: 1246: 1242: 1238: 1233: 1231: 1227: 1219: 1217: 1215: 1209: 1207: 1198: 1193: 1190: 1189: 1188: 1185: 1183: 1178: 1175: 1171: 1164: 1159: 1157: 1150: 1145: 1142: 1138: 1135: 1134:Lisch nodules 1131: 1129: 1126: 1124: 1120: 1116: 1112: 1109: 1105: 1101: 1100: 1099: 1092: 1090: 1088: 1083: 1080: 1078: 1074: 1071:produced via 1070: 1066: 1059: 1054: 1052: 1050: 1042: 1037: 1030: 1028: 1026: 1022: 1017: 1015: 1009: 1002: 1000: 996: 994: 990: 986: 983: 980: 976: 972: 968: 967:neurofibromin 964: 963:chromosome 17 960: 956: 952: 944: 941: 933: 931: 928: 927:breast cancer 921:Breast Cancer 920: 915: 912: 909: 906: 903: 899: 896: 893: 890: 889: 888: 886: 882: 875: 873: 866: 862: 858: 855: 854: 853: 851: 847: 839: 837: 831:Mental Health 830: 828: 826: 825:Acetazolamide 822: 819: 815: 809: 808:Dural ectasia 802:Dural ectasia 801: 799: 797: 793: 789: 781: 779: 777: 771: 763: 758: 755: 752: 749: 746: 743: 736: 733: 732: 730: 722: 717: 712: 709: 706: 704: 701: 699: 695: 691: 690: 686: 681: 677: 676: 671: 664: 659: 655: 652: 649: 645: 642: 639: 635: 631: 627: 624: 621: 618: 617: 616: 613: 611: 607: 606:Schwann cells 603: 595: 590: 588: 585: 577: 572: 569: 566: 562: 559: 556: 553: 550: 546: 545: 544: 537: 532: 528: 524: 521: 518: 514: 513:Lisch nodules 511: 510: 506: 501: 493: 490: 487: 483: 479: 476: 473: 471: 466: 465: 463: 455: 450: 445: 442: 439: 435: 431: 427: 423: 422: 420: 412: 410: 407: 402: 395: 392: 389: 388: 387: 384: 380: 379: 372: 368: 364: 361: 357: 356:dural ectasia 353: 351: 347: 344: 341: 338: 334: 330: 329: 328: 326: 321: 319: 318:hydrocephalus 315: 314:sphenoid bone 311: 307: 300: 295: 292: 289: 286: 283: 280: 277: 276: 275: 267: 260: 256: 249: 247: 234: 232: 219: 217: 209: 205: 204:neurofibromin 201: 196: 194: 190: 186: 182: 178: 174: 170: 169:neurofibromas 166: 165:Lisch nodules 157: 143: 131: 130:chromosome 17 127: 123: 119: 115: 111: 102: 98: 95: 94:ophthalmology 91: 87: 84: 82: 78: 73: 69: 64: 58: 55: 52: 50: 46: 41: 33: 19: 5809: 5789: 5775: 5761: 5747: 5733: 5719: 5694: 5680: 5666: 5625: 5611: 5582: 5553: 5547: 5533: 5519: 5493: 5479: 5465: 5451: 5422: 5408: 5345: 5331: 5317: 5297: 5280: 5266: 5252: 5230: 5216: 5088: 5020: 4978:Neurilemmoma 4966:Neurofibroma 4695:Glioblastoma 4633:brain tumors 4595: 4567: 4466: 4376:Angiomatosis 4368:Phakomatosis 4095: 3787:Heritability 3777:Epidemiology 3703: 3683: 3672: 3648: 3637: 3626: 3611: 3591: 3533: 3529: 3519: 3508:. Retrieved 3504: 3491: 3480:. Retrieved 3475: 3466: 3453: 3442:. Retrieved 3438: 3428: 3395: 3391: 3384: 3357: 3353: 3343: 3324: 3318: 3301: 3297: 3291: 3280:. Retrieved 3276: 3267: 3255:. Retrieved 3251:the original 3246: 3236: 3221: 3186: 3182: 3172: 3145: 3141: 3131: 3096: 3092: 3082: 3057: 3053: 3047: 3012: 3008: 2960: 2956: 2912: 2908: 2898: 2873: 2869: 2849: 2835: 2802: 2798: 2792: 2781:. Retrieved 2777: 2768: 2731: 2727: 2717: 2680: 2676: 2666: 2639: 2635: 2625: 2603:(1): 31–37. 2600: 2596: 2590: 2533: 2529: 2518: 2473: 2469: 2459: 2421:(5): 49254. 2418: 2414: 2404: 2363: 2359: 2348: 2305: 2301: 2291: 2266: 2263:Neurosurgery 2262: 2231:(1): 38–44. 2228: 2224: 2218: 2185: 2181: 2175: 2140: 2136: 2126: 2093: 2089: 2083: 2048: 2044: 1998: 1994: 1988: 1955: 1951: 1945: 1939:Optic glioma 1932: 1928: 1920: 1907: 1896:. Retrieved 1892:the original 1887: 1878: 1859: 1855: 1845: 1812: 1808: 1802: 1767: 1763: 1753: 1718: 1714: 1704: 1677: 1673: 1634:(9): e0165. 1631: 1627: 1579: 1575: 1565: 1554:. Retrieved 1547:the original 1542: 1529: 1518:. Retrieved 1511:the original 1506: 1493: 1456: 1452: 1441: 1427: 1394: 1390: 1384: 1373:. Retrieved 1369:the original 1364: 1355: 1318: 1314: 1286: 1276: 1241:Elephant Man 1234: 1223: 1210: 1202: 1186: 1179: 1174:Astra Zeneca 1168: 1154: 1132:Two or more 1102:Six or more 1096: 1084: 1081: 1063: 1046: 1018: 1010: 1006: 997: 991:activity of 953:caused by a 948: 924: 913: 907: 897: 891: 879: 870: 843: 834: 823: 811: 785: 773: 764:Glial tumors 756: 750: 744: 734: 698:hypertension 614: 602:neurofibroma 599: 596:Neurofibroma 581: 541: 531:optic chiasm 527:optic nerves 470:café au lait 469: 403: 399: 385: 381: 377: 376: 350:Spina bifida 346:Meningoceles 322: 304: 272: 237:people with 235: 220: 197: 189:café au lait 158: 117: 113: 109: 108: 86:Neurosurgery 5847:RASopathies 5575:phosphatase 5392:phosphatase 4837:Neurocytoma 4799:Gliosarcoma 4665:Astrocytoma 4585:Pituicytoma 4205:MMR vaccine 3943:Infodumping 3918:Monotropism 3913:Late talker 3878:Alexithymia 3782:Epigenetics 3705:GeneReviews 3674:MedlinePlus 2476:: 815–821. 1287:Mayo Clinic 1170:Selumetinib 1165:Selumetinib 1107:conditions. 770:Glial tumor 644:Schwannomas 610:fibroblasts 507:Eye disease 360:diverticula 100:Usual onset 90:dermatology 48:Other names 5826:Categories 5702:Zaspopathy 5369:MAP kinase 4982:Schwannoma 4895:Meningioma 4738:Ependymoma 4215:Thiomersal 3958:Echopraxia 3908:Hyperlexia 3650:DiseasesDB 3510:2021-04-27 3482:2023-11-15 3444:2020-06-21 3282:2020-03-05 3277:Genome.gov 2783:2023-11-15 1898:2015-10-27 1862:(2): 102. 1556:2011-05-15 1520:2011-05-15 1375:2015-10-27 1321:(2): 260. 1268:References 1119:Crowe sign 949:NF-1 is a 735:Occurrence 703:Schwannoma 565:cerebellar 460:See also: 417:See also: 337:mesodermal 191:spots and 124:(NF-1), a 5810:See also 5688:Cherubism 5208:Monomeric 5148:G protein 4657:Astrocyte 4605:Pinealoma 4558:Endocrine 4399:Hamartoma 4220:Chelation 3953:Echolalia 3826:Diagnoses 3817:Therapies 3772:Diagnosis 3699:radio/474 3693:neuro/248 3685:eMedicine 3552:1557-2625 3420:247453317 3009:Neoplasia 2843:GeneCards 2734:(1): 12. 2552:2040-2392 2492:1176-6328 2451:263240202 2435:2155-7780 2396:235999769 2380:1471-1788 2322:0009-9163 1995:Neurology 1952:Neurology 1650:2691-3895 1199:Prognosis 1151:Treatment 1055:Diagnosis 1003:Structure 914:Mortality 908:Treatment 898:Diagnosis 892:Frequency 745:Diagnosis 741:patients. 478:Freckling 406:RASopathy 367:scoliosis 340:dysplasia 327:include: 208:RASopathy 177:scoliosis 146:NF-1 gene 81:Specialty 5573:Tyrosine 4887:Meninges 4730:Ependyma 4008:Epilepsy 3948:Stimming 3690:derm/287 3608:Q85.010) 3560:21209351 3476:DailyMed 3412:35289492 3376:24676443 3228:(OMIM): 3213:17297459 3183:Oncogene 3164:16169856 3123:16513807 3074:10029430 3039:12082543 2957:Genomics 2939:24525378 2931:20513137 2760:30962859 2709:21542925 2617:10469434 2570:34983638 2536:(1): 3. 2510:25848279 2443:37816254 2388:34270353 2340:25534182 2283:31350851 2245:10469435 2210:39229702 2202:12822818 2167:19609654 2159:21352477 2118:26650152 2110:20101681 2075:11781870 2067:23163236 2023:26812237 2015:12682321 1980:10198510 1972:16217056 1915:, & 1837:21120799 1829:22907230 1794:24163128 1745:38835893 1737:25913846 1696:26032208 1606:12011145 1483:34012067 1419:20385802 1411:12403561 1347:31602150 1251:See also 1115:axillary 1016:kinase. 982:oncogene 955:mutation 751:Etiology 729:Epilepsy 723:Epilepsy 713:Epilepsy 648:resected 638:fusiform 573:deficit. 371:kyphosis 312:include 193:epilepsy 103:At birth 5749:PRKAR1A 5741:CADASIL 5735:Notch 3 5668:EDARADD 5453:RPS6KA3 4472:Type II 4305:Schools 3792:History 3696:oph/338 3644:D009456 3257:May 16, 3247:BioNews 3204:2760340 3114:1866217 3030:1531708 2987:1783401 2890:1952978 2827:2134734 2807:Bibcode 2799:Science 2751:6434896 2700:3095535 2658:8402499 2561:8729013 2501:4378869 2331:4573679 1785:3954124 1687:5133719 1597:1735122 1474:8354850 1338:6785427 1069:embryos 848:and/or 757:Therapy 636:) as a 571:Spatial 529:or the 515:in the 482:axillae 480:of the 369:and/or 5777:PRKCSH 5763:PRKAG2 5682:SH3BP2 5627:PTPN11 5444:kinase 5388:kinase 5386:Other 5333:ARL13B 4815:neuron 4812:Mature 4648:Glioma 4596:Other: 4569:Sellar 4467:Type I 3797:Memory 3767:Causes 3753:Autism 3679:000847 3633:162200 3622:237.71 3558: 3550: 3418: 3410: 3374: 3331: 3211: 3201: 3162: 3121: 3111: 3072: 3037: 3027: 2985: 2937: 2929: 2888: 2825: 2758: 2748: 2707: 2697: 2683:: 18. 2656: 2636:Cancer 2615: 2568: 2558: 2550: 2508: 2498: 2490: 2449: 2441: 2433: 2394: 2386: 2378: 2338: 2328: 2320: 2281: 2243: 2208: 2200: 2165: 2157: 2116: 2108: 2073: 2065: 2021: 2013: 1978: 1970: 1835: 1827: 1792: 1782: 1743: 1735: 1694: 1684: 1648: 1604: 1594: 1481: 1471: 1417: 1409: 1345: 1335: 989:GTPase 973:. The 881:Cancer 876:Cancer 846:Autism 796:myelin 549:autism 500:lasers 365:Focal 116:), or 5797:XIAP2 5713:Other 5495:STK11 5481:IKBKG 5467:CHEK2 5424:ZAP70 5319:SAR1B 5296:RHO: 5282:RAB27 5268:RAB23 5251:RAB: 5215:RAS: 5198:CGL 2 5169:GNAS1 5003:Other 4481:Other 4288:Lists 3602:Q85.0 3501:(PDF) 3416:S2CID 2935:S2CID 2447:S2CID 2392:S2CID 2206:S2CID 2163:S2CID 2114:S2CID 2071:S2CID 2019:S2CID 1976:S2CID 1833:S2CID 1741:S2CID 1550:(PDF) 1539:(PDF) 1514:(PDF) 1503:(PDF) 1415:S2CID 1228:" by 1121:) or 957:of a 934:Cause 658:spine 472:spots 436:as a 333:fetus 325:spine 310:skull 5791:XIAP 5696:LDB3 5613:MTM1 5584:PTEN 5555:WNK1 5549:WNK4 5535:GRK1 5508:DMPK 5347:ARL6 5299:RAC2 5254:RAB7 5232:KRAS 5218:HRAS 5165:cAMP 3760:Main 3655:8937 3639:MeSH 3628:OMIM 3617:9-CM 3606:ILDS 3556:PMID 3548:ISSN 3408:PMID 3372:PMID 3329:ISBN 3259:2011 3209:PMID 3160:PMID 3119:PMID 3070:PMID 3035:PMID 2983:PMID 2927:PMID 2886:PMID 2823:PMID 2756:PMID 2705:PMID 2654:PMID 2613:PMID 2566:PMID 2548:ISSN 2506:PMID 2488:ISSN 2439:PMID 2431:ISSN 2384:PMID 2376:ISSN 2336:PMID 2318:ISSN 2279:PMID 2241:PMID 2198:PMID 2155:PMID 2106:PMID 2094:152A 2063:PMID 2011:PMID 1968:PMID 1825:PMID 1790:PMID 1733:PMID 1692:PMID 1646:ISSN 1602:PMID 1479:PMID 1407:PMID 1343:PMID 959:gene 850:ADHD 814:dura 739:NF-1 517:iris 456:Skin 243:NF-1 239:NF-1 227:NF-1 223:NF-1 212:NF-1 161:NF-1 154:NF-1 150:NF-1 138:NF-1 134:NF-1 126:gene 114:NF-1 5721:NF2 5521:ATR 5410:BTK 5314:ARF 4932:PNS 4619:CNS 3613:ICD 3593:ICD 3538:doi 3439:FDA 3400:doi 3362:doi 3306:doi 3199:PMC 3191:doi 3150:doi 3146:280 3109:PMC 3101:doi 3062:doi 3025:PMC 3017:doi 2973:hdl 2965:doi 2917:doi 2878:doi 2874:127 2815:doi 2803:249 2746:PMC 2736:doi 2695:PMC 2685:doi 2644:doi 2605:doi 2556:PMC 2538:doi 2496:PMC 2478:doi 2423:doi 2368:doi 2326:PMC 2310:doi 2271:doi 2233:doi 2190:doi 2145:doi 2098:doi 2053:doi 2003:doi 1960:doi 1864:doi 1817:doi 1780:PMC 1772:doi 1723:doi 1682:PMC 1636:doi 1592:PMC 1584:doi 1469:PMC 1461:doi 1399:doi 1333:PMC 1323:doi 1014:Ras 993:Ras 979:Ras 902:MRI 818:CSF 632:or 484:or 202:in 128:on 59:NF1 5828:: 5316:: 5171:: 5025:). 4825:: 3708:: 3688:: 3677:: 3653:: 3642:: 3631:: 3620:: 3600:: 3597:10 3554:. 3546:. 3534:24 3532:. 3528:. 3503:. 3474:. 3437:. 3414:. 3406:. 3396:69 3394:. 3370:. 3358:72 3356:. 3352:. 3302:45 3300:. 3275:. 3245:. 3207:. 3197:. 3187:26 3185:. 3181:. 3158:. 3144:. 3140:. 3117:. 3107:. 3097:15 3095:. 3091:. 3068:. 3058:51 3056:. 3033:. 3023:. 3011:. 3007:. 2995:^ 2981:. 2971:. 2961:11 2959:. 2947:^ 2933:. 2925:. 2913:31 2911:. 2907:. 2884:. 2872:. 2860:^ 2821:. 2813:. 2801:. 2776:. 2754:. 2744:. 2732:17 2730:. 2726:. 2703:. 2693:. 2679:. 2675:. 2652:. 2640:72 2638:. 2634:. 2611:. 2601:89 2599:. 2578:^ 2564:. 2554:. 2546:. 2534:13 2532:. 2528:. 2504:. 2494:. 2486:. 2474:11 2472:. 2468:. 2445:. 2437:. 2429:. 2419:25 2417:. 2413:. 2390:. 2382:. 2374:. 2364:25 2362:. 2358:. 2334:. 2324:. 2316:. 2306:88 2304:. 2300:. 2277:. 2267:86 2265:. 2253:^ 2239:. 2229:89 2227:. 2204:. 2196:. 2186:18 2184:. 2161:. 2153:. 2141:10 2139:. 2135:. 2112:. 2104:. 2092:. 2069:. 2061:. 2049:55 2047:. 2043:. 2031:^ 2017:. 2009:. 1999:60 1997:. 1974:. 1966:. 1956:65 1954:. 1937:: 1919:. 1886:. 1858:. 1854:. 1831:. 1823:. 1813:46 1811:. 1788:. 1778:. 1768:23 1766:. 1762:. 1739:. 1731:. 1719:57 1717:. 1713:. 1690:. 1678:15 1676:. 1672:. 1658:^ 1644:. 1630:. 1626:. 1614:^ 1600:. 1590:. 1580:39 1578:. 1574:. 1541:. 1505:. 1477:. 1467:. 1457:23 1455:. 1451:. 1413:. 1405:. 1395:17 1393:. 1363:. 1341:. 1331:. 1319:52 1317:. 1313:. 1301:^ 1285:. 1216:. 1214:UK 1089:. 995:. 900:. 852:. 798:. 600:A 496:CO 233:. 183:, 175:, 156:. 92:, 88:, 5552:/ 5390:/ 5167:/ 5058:e 5051:t 5044:v 4980:/ 4934:: 4640:) 4635:, 4631:( 4571:: 4542:e 4535:t 4528:v 4418:) 4414:( 4360:e 4353:t 4346:v 3745:e 3738:t 3731:v 3615:- 3604:( 3595:- 3585:D 3562:. 3540:: 3513:. 3485:. 3447:. 3422:. 3402:: 3378:. 3364:: 3337:. 3312:. 3308:: 3285:. 3261:. 3215:. 3193:: 3166:. 3152:: 3125:. 3103:: 3076:. 3064:: 3041:. 3019:: 3013:4 2989:. 2975:: 2967:: 2941:. 2919:: 2892:. 2880:: 2829:. 2817:: 2809:: 2786:. 2762:. 2738:: 2711:. 2687:: 2681:6 2660:. 2646:: 2619:. 2607:: 2572:. 2540:: 2512:. 2480:: 2453:. 2425:: 2398:. 2370:: 2342:. 2312:: 2285:. 2273:: 2247:. 2235:: 2212:. 2192:: 2169:. 2147:: 2120:. 2100:: 2077:. 2055:: 2025:. 2005:: 1982:. 1962:: 1901:. 1872:. 1866:: 1860:3 1839:. 1819:: 1796:. 1774:: 1747:. 1725:: 1698:. 1652:. 1638:: 1632:2 1608:. 1586:: 1559:. 1523:. 1485:. 1463:: 1435:. 1421:. 1401:: 1378:. 1349:. 1325:: 1296:. 1143:. 1117:( 904:. 682:. 567:. 519:. 498:2 488:. 440:. 112:( 34:. 20:)

Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.