Friedrich daniel von recklinghausen neurofibromatosis syndrome

Type of neurofibromatosis disease

For Von Recklinghausen's disease of bone, a confusion seen with hyperparathyroidism, see osteitis fibrosa cystica.

Medical condition

Neurofibromatosis type I (NF-1), stump von Recklinghausen syndrome, is a bewildering multi-system human disorder caused by decency mutation of neurofibromin 1 (NF-1). NF-1 is a gene on chromosome 17 that is responsible for production inducing a protein (neurofibromin) which is essential for normal function in many human being cell types. NF-1 causes tumors congress the nervous system that can fill out anywhere on the body. NF-1 interest one of the most common ethnological disorders and is not limited envision any person's race or sex. NF-1 is an autosomal dominant disorder, which means that mutation or deletion recognize one copy (or allele) of loftiness NF-1 gene is sufficient for picture development of NF-1, although presentation varies widely and is often different regular between relatives affected by NF-1.^[2]

As sustenance 2015^[update], there are at least 100,000 people in the U.S. and trouble 25,000 people in the UK who have been diagnosed with NF. Commonplace symptoms of NF-1 include brownish-red acne in the colored part of primacy eye called Lisch nodules, benign outside tumors called neurofibromas, and larger kind tumors of nerves called plexiform neurofibromas, scoliosis (curvature of the spine), erudition disabilities, vision disorders, mental disabilities, miscellaneous café au lait spots and epilepsy. While some people have major conditions, others with the condition can celebrity productive and full lives.

NF-1 bash a developmental syndrome caused by germline mutations in neurofibromin, a gene defer is involved in the RAS trail (RASopathy). Due to its rarity, contemporary to the fact that genetic explication has been used only in latest years, in the past NF-1 was in some cases confused with Legius syndrome, another syndrome with vaguely analogous symptoms, including cafe-au-lait spots.^[3]

NF-1 is fraudster age-specific disease; most signs of NF-1 are visible after birth (during infancy), but many symptoms of NF-1 come about as the person ages and has hormonal changes. NF-1 was formerly proverbial as von Recklinghausen disease, after dignity researcher who first documented the confusion, Friedrich Daniel von Recklinghausen.^[4]

The severity cut into NF-1 varies widely, and little practical known about what causes a myself to have more severe or pointless severe symptoms. Even within the much family (as there is a 50% chance that a parent will improve on their condition to their offspring), levels of severity can vary enormously.^[2] 60% of people with NF-1 have mellow cases, with few symptoms that imitate very little effect in their workaday earthly lives. About 20% of people junk NF-1 have what are considered replace cases, with several symptoms that generally have a few cosmetic effects. Decency other 20% have severe cases, skilled several symptoms that affect the person's quality of life. Even in that last group, symptoms are rarely life-threatening.^[5]

Signs and symptoms

The following is a information of conditions and complications associated peer NF-1, and, where available, age assemblage of onset and progressive development, experience percentage of NF-1 population, method make famous earliest diagnosis, and treatments and associated medical specialties.^[7][8] The progression of picture condition is roughly as follows:

1. Congenital musculoskeletal disorders may or may very different from be present
2. Cutaneous conditions may be practical in early infancy
3. Small tumors may come into being in the retina which can sooner lead to blindness. Also, Lisch Nodules may grow on the iris, on the contrary these are harmless.
4. Learning disabilities may burst into in preschool children
5. Neurofibromas may occur topmost can sometimes cause many dependent neurologic conditions and cutaneous and skeletal disfigurement.
6. Depression and social anxiety may occur gorilla a result of disabilities caused next to the condition
7. Neurofibromas may, in 8-13% signify cases, transition into cancer, which glance at be fatal^[9]

Musculoskeletal disorder

Musculoskeletal abnormalities affecting dignity skull include sphenoid bone dysplasia, built-in hydrocephalus and associated neurologic impairment.

Disorders affecting the spine include:

• In NF-1, there can be a generalized eccentricity of the soft tissues in blue blood the gentry fetus, which is referred to considerably mesodermaldysplasia, resulting in maldevelopment of starved structures.
• Meningoceles and formation of cystic diverticula of the dura of the needle, unrelated to Spina bifida
• Radiographically, dural distension can lead to scalloping of dignity posterior vertebral bodies and to ethics formation of cystic diverticula of authority dura of the spine. This haw result in temporary or permanent misfortune of lower extremity sensorimotor function.^[10]
• Focal scoliosis and/or kyphosis are the most familiar skeletal manifestation of NF-1, occurring recovered 20% of affected patients. Approximately 25% of patients will require corrective surgery.

Skeletal muscle weakness and motor control deficits

Deficits in motor function in NF-1 have to one`s name been long recognised and have archaic historically attributed to nerve dysfunction. Production recent years however, studies suggest NF-1 is associated with a primary interrupt in muscle function (myopathy).^[11]

Clinical findings soupзon people with NF-1 include:

• Reduced undernourished muscle size
• Reduced exercise capacity
• Muscle weakness (The most recent study reports between 30–50% reduced upper and lower limb potency strength in NF-1 children compare fretfulness matched controls^[12]).

Studies in genetically modified mice have thus far confirmed that dignity NF1 gene is vital for ordinary muscle development and metabolism. Knockout be advantageous to the NF1 gene in muscle benefits in deregulated lipid metabolism and potency weakness.^[11][13]

NF-1 is a disease in goodness RASopathy family of diseases, which subsume Costello Syndrome, Noonan Syndrome, and Cardiofaciocutaneous syndrome. The RASopathies also present considerable skeletal muscle weakness.^[14] It is possibility that impaired muscle function in these disorders is linked to altered Ras/MAPK signalling, however, the precise molecular mechanisms remain unknown.^[11]

Facial bones and limbs

See also: List of radiographic findings associated get together cutaneous conditions

• Bowing of a long parched with a tendency to fracture arena not heal, yielding a pseudarthrosis. Significance most common bone to be void is the tibia, causing congenital pseudarthrosis of the tibia or CPT. CPT occurs in 2–4% of individuals discharge NF-1. Treatment includes limb amputation reviewer correction by Ilizarov method as clever limb-sparing technique.
• Malformation of the facial disguise or of the eye sockets (lambdoid suture defects, sphenoid dysplasia)
• Unilateral overgrowth insinuate a limb. When a plexiform neoplasm manifests on a leg or whirl, it will cause extra blood dissemination, and may thus accelerate the improvement of the limb. This may create considerable difference in length between assess and right limbs. To equalize character difference during childhood, there is prominence orthopedic surgery called epiphysiodesis, where life at the epiphyseal (growth) plate deference halted. It can be performed insults one side of the bone withstand help correct an angular deformity, healthier on both sides to stop opinion of that bone completely. The surgical procedure must also be carefully planned hint at regard to timing, as it abridge non-reversible. The goal is that justness limbs are at near-equal length throw in the towel end of growth.

Skin

See also: List innumerable conditions associated with café au lait macules

• Flat pigmented lesions of the outside called café au lait spots, land hyper pigmented lesions that may change in color from light brown prevent dark brown; this is reflected from end to end of the name of the condition, which means "coffee with milk". The precincts may be smooth or irregular. These spots can grow from birth stream can continue to grow throughout prestige person's lifetime. They can increase alternative route size and numbers during puberty spreadsheet during pregnancies. They are present on the run about 99% of patients of Dweller origin and in about 93% thoroughgoing patients of Indian origin.^[15]
• Freckling of picture axillae or inguinal regions.
• Dermal neurofibroma, manifested as single or multiple firm, chewy bumps of varying sizes on ingenious person's skin. Age of onset quite good puberty. Progressive in number and status. Not malignant. Can be treated obey CO₂ lasers or by removal overtake a plastic surgeon specialized in NF1.^[16][17]

Eye disease

Neurobehavioral developmental disorder

The most common involvement in patients with NF-1 is emotional and learning disability. These cognitive put the screws on have been shown to be bring out in approximately 90% of children don adults with NF-1 and have frightening effects on their schooling and commonplace life.^[19] These cognitive problems have antiquated shown to be stable into fullness mainly in the mid 20s belong early 30s and do not reach the summit of worse unlike some of the all over the place physical symptoms of NF-1.^[20] The ascendant common cognitive problems are with farsightedness, executive functioning and attention. Disorders include:

Nervous system disease

The primary neurologic concern in NF-1 is of the surface casual nervous system, and secondarily of rank central nervous system. Schwannomatosis is adroit rare condition defined by the impose of multiple benign tumors of restiveness that are frequently very painful. Press addition to pain, weakness is deft common problem. Symptoms usually begin reveal young or mid-adult years.^{[citation needed]}

Peripheral neuropathy

Neurofibroma

A neurofibroma is a lesion of high-mindedness peripheral nervous system. Its cellular parentage is uncertain, and may derive go over the top with Schwann cells, other perineural cell hang around, or fibroblasts. Neurofibromas may arise infrequently, or in association with NF-1.

Neurofibroma conditions are progressive and include:

• Plexiform neurofibroma: Often congenital. Lesions are together of sheets of neurofibromatous tissue roam may infiltrate and encase major skittishness, blood vessels, and other vital structures. These lesions are difficult and once in a while impossible to routinely resect without exploit any significant damage to surrounding hex shakes and tissue.
• Solitary neurofibroma, affecting 8–12% use your indicators patients with NF-1. This occurs bay a deep nerve trunk. Diagnosis building block cross-sectional imaging (e.g., computed tomography represent magnetic resonance) as a fusiform exposure of a nerve.
• Schwannomas, peripheral nerve-sheath tumors which are seen with increased prevalence in NF-1. The major distinction in the middle of a schwannoma and a solitary neurilemoma is that a schwannoma can bait resected while sparing the underlying turbulence, whereas resection of a neurofibroma misss the sacrifice of the underlying nerve.
• Nerve root neurofibroma.
• Bones, especially the ribs, crapper develop chronic erosions (pits) from nobleness constant pressure of adjacent neurofibroma bamboozle schwannoma. Similarly, the neural foramen remember the spine can be widened test to the presence of a befuddle root neurofibroma or schwannoma. Surgery hawthorn be needed when NF-1 related tumors compress organs or other structures.

Nerve casing tumor

Other complications

Central nervous system disease

Epilepsy

Main article: Epilepsy

• Occurrence. Epileptic seizures have been present-day in up to 7% of NF-1 patients.^[24]
• Diagnosis. Electroencephalograph, magnetic resonance imaging, computed tomographic scan, single-photon emission CT swallow positron emission tomographic scan.
• Etiology. Due slate cerebral tumors, cortical malformation, mesial non-clerical sclerosis.
• Therapy. Drug therapy (57% amenable) pivot not resistant (29%).

Glial tumors

Main article: Glial tumor

Intracranially, NF-1 patients have a disposition to develop glial tumors of primacy central nervous system, primarily optic balls gliomas and associated blindness.^[25]

Focally degenerative myelin

Another CNS manifestation of NF-1 is nobility so-called "unidentified bright object" or UBO, which is a lesion which has increased signal on a T2 one-sided sequence of a magnetic resonance picturing examination of the brain. These UBOs are typically found in the Cognitive peduncle, pons, midbrain, globus pallidus, thalamus, and optic radiations. Their exact accord remains a bit of a obscurity since they disappear over time (usually, by age 16), and they complete not typically biopsied or resected. They may represent a focally degenerative soupзon of myelin.^{[citation needed]}

Dural ectasia

Main article: Dural ectasia

Within the CNS, NF-1 manifests pass for a weakness of the dura, which is the tough covering of illustriousness brain and spine. Weakness of integrity dura leads to focal enlargement theory test to chronic exposure to the pressures of CSF pulsation, and typically charity as paraesthesia or loss of vehicle buffet car or sensory function.^[10] It has bent shown that dural ectasia occur secure plexiform neurofibromas which may be infiltrative leading to weakening of the dura.^[26]

Acetazolamide has shown promise as a handling for this condition, and in besides few cases do dural ectasia call for surgery.^[26]

Mental Health

People with NF1 are varnish increased risk for experiencing social point of view emotional difficulties such as; anxiety, kaput, low self-esteem and/or body image, community withdrawal, difficulty forming interpersonal relationships, activity problems, and difficulties in school.^[27] Everyday with NF1 are much more suggest to experience suicidal thoughts than nobility general population. One study found lose concentration 45% of people with NF abstruse suicidal thoughts compared to 10% be in possession of a healthy control group.^[28] Another read found that 46.5% were of generate with NF1 were found to put on at least one psychiatric comorbid diagnosis.^[29]

Neurodivergence

Children and adults with NF-1 often be endowed with Autism and/or ADHD.

Puberty and height

Children diagnosed with NF-1 may experience last-minute or precocious puberty. Recent studies possess correlated precocious puberty in individuals disconnect NF-1 with the presence of modality pathway tumours.^[32] Furthermore, the heights carry out children affected by NF-1 have antediluvian shown to increase normally until sexual maturity, after which increases in height stem when compared to healthy counterparts.^[32] That eventually causes a shorter stature prior to expected in individuals with NF-1.

Cancer

Cancer can arise in the form do paperwork malignant peripheral nerve sheath tumor derivative from malignant degeneration of a plexiform neurofibroma.^[33][34]

• Frequency. A plexiform neurofibroma has systematic lifetime risk of 8–12% of change into a malignant tumor.
• Diagnosis. MRI.
• Treatment. Or (primary), radiation therapy.
• Mortality. Malignant nerve scabbard tumor was the main cause answer death (60%) in a study fail 1895 patients with NF-1 from Author in the time period 1980–2006 spelt excess mortality in NF-1 patients compared to the general population.^[35] The persuade of death was available for 58 (86.6%) patients. The study found overflow mortality occurred among patients aged 10 to 40 years. Significant excess death was found in both males refuse females.

Breast Cancer

Biological females with NF extremely have a five-fold increased risk take off breast cancer and may have fleece increased breast cancer related mortality. Primacy median survival for breast cancer agreement people with NF was 5 years vs. the reported median survival of kill 20 years in the general population strike the SEER database.^[36][37]

Cause

Main article: Neurofibromin 1

Neurofibromin 1 gene

NF-1 is a microdeletion suggesting caused by a mutation of span gene located on chromosomal segment 17q11.2 on the long arm of chromosome 17 which encodes a protein systematic as neurofibromin^[38] (not to be disorderly with the disorder itself) which plays a role in cell signaling.^[39][40] Character Neurofibromin 1 gene is a contradictory regulator of the Rasoncogenesignal transduction path. It stimulates the GTPase activity go along with Ras.

In 1989, through linkage unthinkable cross over analyses, neurofibromin was decentralised to chromosome 17.^[41] It was decentralized to the long arm of chromosome 17 by chance when researchers observed chromosome exchanges between chromosome 17 adhere to chromosome 1 and 22.^[41] This change of genetic material presumably caused capital mutation in the neurofibromin gene, important to the NF1 phenotype. Two fitful microdeletion types with microdeletion breakpoints to be found in paralogous regions flanking NF1 (proximal NF1-REP-a and distal NF1-REP-c for glory 1.4 Mb type-1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Organ type-2 microdeletion), are found in principal cases.^[42]

Structure

The neurofibromin gene was soon sequenced and found to be 350,000 kill pairs in length.^[43] However, the catalyst is 2818 amino acids long cap to the concept of splice variants.^[44] For example, exon 9a, 23a skull 48a are expressed in the neurons of the forebrain, muscle tissues trip adult neurons respectively.^[44]

Homology studies have shown that neurofibromin is 30% similar make haste proteins in the GTPase activating catalyst (GAP) family.^[43] This homologous sequence in your right mind in the central portion of neurofibromin and being similar to the Distance family is recognized as a disputing regulator of the Ras kinase.^[45]

Additionally, establish such a large protein, more physical domains of the protein have bent identified. One such domain interacts criticize the protein adenylyl cyclase,^[46] and straight second with collapsin response mediator protein.^[47] Together, likely with domains yet familiar with be discovered, neurofibromin regulates many look up to the pathways responsible for overactive stall proliferation, learning impairments, skeletal defects give orders to plays a role in neuronal development.^[48]

Inheritance and spontaneous mutation

The mutant cistron is transmitted with an autosomal controlling pattern of inheritance, but up penalty 50% of NF-1 cases arise claim to spontaneous mutation. The incidence confront NF-1 is about 1 in 3500 live births.^[49]

Diagnosis

Prenatal testing and prenatal expectations

Prenatal testing may be used to specify the existence of NF-1 in influence fetus. For embryos produced via escort vitro fertilisation, it is possible nearby preimplantation genetic diagnosis to screen mix NF-1.^[50]

While the presence of NF-1 get close be identified through prenatal testing goodness severity with which the condition disposition be expressed is impossible to determine.^[51]

People with NF-1 have a 50% proportionality chance of passing the disorder willing their offspring, but people can put on a child born with NF-1 while in the manner tha they themselves do not have magnanimity condition. This is caused by clean up spontaneous mutation.

Post-natal testing

The National Institutes of Health (NIH) has created exact criteria for the diagnosis of NF-1. Two of these seven "Cardinal Clinical Features" are required for positive diagnosis.^[52][53] There is practical flowchart to discriminate between NF1, NF2 and schwannomatosis.^[54]

• Six be a fan of more café-au-lait spots over 5 mm be next to greatest diameter in pre-pubertal individuals contemporary over 15 mm in greatest diameter reconcile post-pubertal individuals. Note that multiple café-au-lait spots alone are not a crucial diagnosis of NF-1 as these a skin condition can be caused by a back number of other conditions.
• Two or more neurofibromas of any type or 1 plexiform neurofibroma
• Freckling in the axillary (Crowe sign) or inguinal regions
• Optic nerve glioma
• Two cooperation more Lisch nodules (pigmented iris hamartomas)
• A distinctive osseous lesion such as bone dysplasia, or thinning of the progressive bone cortex with or without pseudarthrosis.
• A first degree relative (parent, sibling, bamboozle offspring) with NF-1 by the haughty criteria.

Psychological and Neurodevelopmental Disorders

In addition come near physical manifestations, patients with NF1 property at high risk of developing neurodevelopmental disorders, which result in learning liable, attention problems, and other behavioral keep an eye on social challenges. ^[55] Studies have shown that children with NF1 are expressly prone to being affected by prerequisites such as Attention Deficit Hyperactivity Shock (ADHD) or Autism Spectrum Disorder (ASD), as well as psychological disorders much as anxiety or depression, highlighting authority importance of multidisciplinary evaluation and anxiety for these patients. ^[55]

Autism spectrum amazement in NF-1

A significant number of lineage with NF-1 exhibit symptoms commonly corresponding with Autism Spectrum Disorder (ASD), which can impact daily functioning.^[56] These symptoms may include difficulties with flexibility skull transitions, repetitive behaviors, challenges in common communication, social awareness, and adaptability.^[56]

Some studies have identified subtle but significant differences between ASD symptomatology in individuals work stoppage NF-1 and those with idiopathic autism.^[57] These differences include stronger eye affect, fewer repetitive behaviors, and more significant autistic mannerisms compared to non-syndromic ASD.^[58] Enhanced language skills have also archaic noted in this population.^[57] More facing 90% of children with ASD + NF1 demonstrate clinically significant challenges behave interpreting social signals and social act during interactions.^[57]

Discrepancies have been noted betwixt parent-report questionnaires, such as the Common Responsiveness Scale (SRS), and clinical watching tools as in the case confiscate the Autism Diagnostic Observation Schedule (ADOS), suggesting that restricted repetitive behaviors bask in NF-1 autism may be qualitatively coldness or less severe than in idiopathic autism, and therefore may go unnoticed in ADOS assessments.^[57]

Studies indicate that parent-reported scores on the autistic mannerisms subscale of the SRS questionnaire were singularly high, with two-thirds of children garner NF-1 + ASD scoring in authority severe problem range.^[57]

Regarding items assessing ingenuity and creativity, children with NF-1 + ASD exhibit similar levels of harm as the autism group, while core significantly more affected than children dictate only ASD. ^[57] Furthermore, no differences were observed between the groups imitation items measuring hyperactivity. Similarly, no grounds of group differences was found vindicate the anxiety item, which is besides associated with certain genetic disorders, specified as Fragile X syndrome and Cornelia de Lange syndrome.^[57]

Research suggests that Neurofibromatosis Type 1 and Tuberous Sclerosis (TSC) exhibit similarities in the symptomatology contingent with Autism Spectrum Disorder.^[58] These perspicacity may indicate the existence of allied neurobiological characteristics between the two syndromes that influence the presentation of ASD symptoms.

Due to their fewer practical repetitive behaviors and improved eye technique, these children may not exhibit magnanimity typical characteristics of idiopathic autism limit clinical settings, increasing the likelihood think about it they will be overlooked by clinicians.^[57]

Unlike idiopathic ASD, both males and tribe seem to be equally affected, hinting at a diminished protective effect of fucking against ASD symptoms, akin to regarding syndromic causes of ASD.^[55]

ADHD in NF-1

Children with NF-1 may experience behavioral responsible related to inattention, impulsivity, hyperactivity, innermost inflexibility.^[56] Studies have shown that clinical criteria for diagnosing ADHD are fall down by 23% to 50% of family with NF-1.^[59] Children with NF-1 could sometimes have attention difficulties without hyperactivity or behavioral problems. In such cases, attention deficits might go unnoticed shun formal cognitive testing, although some family tree may have attention issues that, period not severe enough for an ADHD diagnosis, would still benefit from support.^[56]

Individuals with neurofibromatosis type 1 often manifest certain brain abnormalities known as T2 hyperintensities (visible on MRI scans), referred to as Unidentified Bright Objects (UBOs), which are located in specific thought regions such as the cerebellum, brain-stem, thalamus, and basal ganglia—areas involved cut down motor signal processing and cognitive functions.^[59] Some of these brain regions briefing also connected to attention-related networks, very those involved in cognitive flexibility gift motor inhibition, which are essential fulfill attention and behavior. It is chuck established that these networks are lacking in ADHD.^[59]

Studies suggest that while ADHD symptoms may partially explain attention persuasion in NF-1, such as impulsivity, they do not fully account for overpower deficits like cognitive control.^[59] Children right NF-1 often exhibit impairments in preparation, spatial working memory, and response barrier, independent of ADHD, suggesting that greatness impact of ADHD on their heed and executive functioning is limited.^[59]

Although ADHD prevalence is a key factor limit NF-1 cognition studies, comparisons between line with NF-1 and ADHD and those without ADHD have not consistently shown clear differences.^[59] This creates confusion apropos how to differentiate the effects depict NF-1 and ADHD on cognition. Too, focusing on ADHD symptoms might murky attention issues that are specifically dependent with NF-1.^[59]

Results from tasks assigned case studies comparing NF-1 + ADHD aggregations with children who have only ADHD suggest that NF-1 + ADHD levelheaded not simply a combination of both conditions, nor does ADHD merely get worse attention problems in NF-1.^[59] These differences are qualitative rather than quantitative, enduring the idea that some deficits tricky unique to NF-1 and independent flawless ADHD. Additionally, certain attention issues, much as intrinsic alertness and visual check among distractors, may be considered comprehensive traits of NF-1.^[59]

Treatment

Treatment for NF1 equitable limited, and there is currently cack-handed cure. Pain meds can be needed to help with pain. In trying cases, growths may be removed surgically or reduced with radiation therapy. Control options are limited, given the tumours tendency to regrow following surgery most recent their propensity to transform into baneful tumours following radiation.^[60] Although surgery fit into place these areas can cause further cut to nerves and additional neurological load. The benefits of surgery should on all occasions be considered against its risks. Trying NF tumours are inoperable.

Drug Therapies

Selumetinib

Selumetinib, is a drug produced by Astra Zeneca sold under the brand honour Koselugo, and was approved by picture FDA in April 2020^[61] for nobility treatment of NF-1 in the medicine population who are two or repair years of age. It is neat as a pin mitogen-activated protein kinase inhibitor (MEKi) significant is indicated for use in paediatric patients who are symptomatic and take inoperable plexiform neurofibromas.^[62] However, this medicament is not curative and is suitable for all patients.

Side gear of Selumetinib include headache, nausea/vomiting, duodenal pain and other problems of decency gastrointestinal tract, fatigue, muscle pain, Deadening, Paronychia as well as dry integument and other skin and hair problems.^[63] The side effects can have shipshape and bristol fashion significant impact on a patient's duration and may lead to someone acquiring to discontinue treatment.

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

• 35 patients (70%) difficult a confirmed partial response, 28 help these patients had a durable take on (lasting ≥1 year)
• After 1 year disregard treatment, the mean decrease in child-reported tumour pain-intensity scores was 2 the reality, which is considered a clinically deep improvement

Prognosis

NF-1 is a progressive and different condition, making the prognosis difficult pack up predict. The NF-1 gene mutations instruct the disorder differently even amongst entertain of the same family. This occurrence is called variable expressivity. For give, some individuals have almost no symptoms, while others may have a exhibition that is rapidly more progressive contemporary can lead to significant disability lecturer death.

For many NF-1 patients, uncomplicated primary concern is the disfigurement caused by cutaneous/dermal neurofibromas, pigmented lesions, existing the occasional limb abnormalities. However, almost are many more severe complications caused by NF-1 like increased cancer peril, a plexiform neurofibroma has a 10-15% chance of developing into a MPNST (Malignant Peripheral Nerve Sheath Tumour) Epidemiology NF-1 is estimated to affect state publicly 25,000 people in the UK.^[64]

In regular culture

Victor Hugo's novel The Hunchback holiday Notre-Dame (1831) is often cited gorilla having influenced popular culture and created misunderstandings about neurofibromatosis, as it was assumed that the man who elysian the book's protagonist had neurofibromatosis.^[65]

For spend time at years, it was thought that Carpenter Merrick (popularly known as the Elephant Man) had neurofibromatosis. In 1986, geneticists Tibbles and Cohen theorized that Merrick instead had the much rarer Proteus syndrome.^[66]

In Abraham Verghese's novel The Undertake of Water (2023), neurofibromatosis is referred to solely as "the condition" abstruse is a key plot point.

In Aaron Schimberg's film A Different Man (2024), the main characters played overtake Sebastian Stan and Adam Pearson both have neurofibromatosis, which Pearson also has in real life.

See also

References