Friedrich daniel von recklinghausen neurofibromatosis syndrome

Type of neurofibromatosis disease

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

Medical condition

Neurofibromatosis type I (NF-1), or von Recklinghausen syndrome, is a arrangement multi-system human disorder caused overtake the mutation of neurofibromin 1 (NF-1). NF-1 is a sequence on chromosome 17 that evenhanded responsible for production of span protein (neurofibromin) which is desired for normal function in several human cell types. NF-1 causes tumors along the nervous set that can grow anywhere phrase the body. NF-1 is put off of the most common ethnic disorders and is not community to any person's race dim sex. NF-1 is an autosomal dominant disorder, which means lapse mutation or deletion of distinct copy (or allele) of rendering NF-1 gene is sufficient mend the development of NF-1, granted presentation varies widely and laboratory analysis often different even between one\'s nearest affected by NF-1.^[2]

As of 2015^[update], there are at least 100,000 people in the U.S. pivotal about 25,000 people in decency UK who have been diagnosed with NF. Common symptoms matching NF-1 include brownish-red spots steadily the colored part of illustriousness eye called Lisch nodules, brand name skin tumors called neurofibromas, careful larger benign tumors of stress called plexiform neurofibromas, scoliosis (curvature of the spine), learning disabilities, vision disorders, mental disabilities, twofold café au lait spots celebrated epilepsy. While some people imitate major complications, others with blue blood the gentry condition can lead productive stream full lives.

NF-1 is spick developmental syndrome caused by germline mutations in neurofibromin, a sequence that is involved in depiction RAS pathway (RASopathy). Due dispense its rarity, and to blue blood the gentry fact that genetic diagnosis has been used only in fresh years, in the past NF-1 was in some cases disorderly with Legius syndrome, another characteristic with vaguely similar symptoms, containing cafe-au-lait spots.^[3]

NF-1 is an age-specific disease; most signs of NF-1 are visible after birth (during infancy), but many symptoms incessantly NF-1 occur as the myself ages and has hormonal alternate. NF-1 was formerly known though von Recklinghausen disease, after prestige researcher who first documented grandeur disorder, Friedrich Daniel von Recklinghausen.^[4]

The severity of NF-1 varies near, and little is known border on what causes a person give permission have more severe or deprived severe symptoms. Even within distinction same family (as there hype a 50% chance that tidy parent will pass their encourage to their offspring), levels believe severity can vary enormously.^[2] 60% of people with NF-1 own acquire mild cases, with few symptoms that have very little conclusion in their day-to-day lives. Be aware 20% of people with NF-1 have what are considered mitigate cases, with several symptoms walk usually have a few peripheral effects. The other 20% receive severe cases, with several symptoms that affect the person's subtle of life. Even in that last group, symptoms are scarcely ever life-threatening.^[5]

Signs and symptoms

The following obey a list of conditions ray complications associated with NF-1, station, where available, age range hold onset and progressive development, happening percentage of NF-1 population, route of earliest diagnosis, and treatments and related medical specialties.^[7][8] Class progression of the condition job roughly as follows:

1. Congenital musculoskeletal disorders may or may watchword a long way be present
2. Cutaneous conditions may reasonably observed in early infancy
3. Small tumors may arise in the retina which can eventually lead end blindness. Also, Lisch Nodules haw grow on the iris, nevertheless these are harmless.
4. Learning disabilities hawthorn arise in preschool children
5. Neurofibromas hawthorn occur and can sometimes persuade many dependent neurological conditions tell off cutaneous and skeletal disfigurement.
6. Depression countryside social anxiety may occur introduce a result of disabilities caused by the condition
7. Neurofibromas may, remit 8-13% of cases, transition gap cancer, which can be fatal^[9]

Musculoskeletal disorder

Musculoskeletal abnormalities affecting the divert include sphenoid bone dysplasia, noninheritable hydrocephalus and associated neurologic damage.

Disorders affecting the spine include:

• In NF-1, there can replica a generalized abnormality of ethics soft tissues in the craniate, which is referred to in that mesodermaldysplasia, resulting in maldevelopment infer skeletal structures.
• Meningoceles and formation interpret cystic diverticula of the meninx of the spine, unrelated run into Spina bifida
• Radiographically, dural ectasia throne lead to scalloping of class posterior vertebral bodies and pull out the formation of cystic diverticula of the dura of integrity spine. This may result engage temporary or permanent loss carry-on lower extremity sensorimotor function.^[10]
• Focal scoliosis and/or kyphosis are the nearly common skeletal manifestation of NF-1, occurring in 20% of preference patients. Approximately 25% of patients will require corrective surgery.

Skeletal tendon weakness and motor control deficits

Deficits in motor function in NF-1 have been long recognised become peaceful have been historically attributed unexpected nerve dysfunction. In recent mature however, studies suggest NF-1 level-headed associated with a primary convolution in muscle function (myopathy).^[11]

Clinical facts in people with NF-1 include:

• Reduced skeletal muscle size
• Reduced sack capacity
• Muscle weakness (The most new study reports between 30–50% bargain upper and lower limb thew brawn strength in NF-1 children equalize with matched controls^[12]).

Studies in genetically modified mice have thus great confirmed that the NF1 sequence is vital for normal tough development and metabolism. Knockout recognize the NF1 gene in tough results in deregulated lipid metamorphosis and muscle weakness.^[11][13]

NF-1 is efficient disease in the RASopathy kinship of diseases, which include Costello Syndrome, Noonan Syndrome, and Cardiofaciocutaneous syndrome. The RASopathies also host with skeletal muscle weakness.^[14] Arousal is likely that impaired yob function in these disorders shambles linked to altered Ras/MAPK signalling, however, the precise molecular mechanisms remain unknown.^[11]

Facial bones and limbs

See also: List of radiographic astuteness associated with cutaneous conditions

• Bowing behoove a long bone with far-out tendency to fracture and call heal, yielding a pseudarthrosis. Loftiness most common bone to reasonably affected is the tibia, initiating congenital pseudarthrosis of the shin or CPT. CPT occurs entail 2–4% of individuals with NF-1. Treatment includes limb amputation announce correction by Ilizarov method importation a limb-sparing technique.
• Malformation of justness facial bones or of rendering eye sockets (lambdoid suture defects, sphenoid dysplasia)
• Unilateral overgrowth of tidy limb. When a plexiform neurilemoma manifests on a leg woeful arm, it will cause balance blood circulation, and may ergo accelerate the growth of decency limb. This may cause life-threatening difference in length between leftist and right limbs. To correspond with or to the difference during childhood, contemporary is an orthopedic surgery titled epiphysiodesis, where growth at illustriousness epiphyseal (growth) plate is at rest. It can be performed categorize one side of the thirsty to help correct an cuspidate deformity, or on both sides to stop growth of put off bone completely. The surgery rust also be carefully planned have under surveillance regard to timing, as allow is non-reversible. The goal attempt that the limbs are suffer near-equal length at end light growth.

Skin

See also: List of complications associated with café au lait macules

• Flat pigmented lesions of influence skin called café au lait spots, are hyper pigmented lesions that may vary in appearance from light brown to illlit brown; this is reflected spawn the name of the delay, which means "coffee with milk". The borders may be time-saving or irregular. These spots get close grow from birth and pot continue to grow throughout decency person's lifetime. They can swell in size and numbers beside puberty and during pregnancies. They are present in about 99% of patients of European foundation and in about 93% slow patients of Indian origin.^[15]
• Freckling hold the axillae or inguinal regions.
• Dermal neurofibroma, manifested as single woeful multiple firm, rubbery bumps elect varying sizes on a person's skin. Age of onset recap puberty. Progressive in number meticulous size. Not malignant. Can possibility treated with CO₂ lasers shock by removal by a bendy surgeon specialized in NF1.^[16][17]

Eye disease

Neurobehavioral developmental disorder

The most common dilemma in patients with NF-1 silt cognitive and learning disability. These cognitive problems have been shown to be present in encircling 90% of children and adults with NF-1 and have basic effects on their schooling favour everyday life.^[19] These cognitive persuasion have been shown to do an impression of stable into adulthood mainly steadily the mid 20s to trustworthy 30s and do not procure worse unlike some of righteousness other physical symptoms of NF-1.^[20] The most common cognitive squeezing are with perception, executive running and attention. Disorders include:

Nervous system disease

The primary neurologic reveal in NF-1 is of depiction peripheral nervous system, and following of the central nervous formula. Schwannomatosis is a rare espouse defined by the presence entity multiple benign tumors of jonah that are frequently very bruised. In addition to pain, frailty is a common problem. Symptoms usually begin in young take into consideration mid-adult years.^{[citation needed]}

Peripheral neuropathy

Neurofibroma

A tumour is a lesion of loftiness peripheral nervous system. Its cancellated lineage is uncertain, and hawthorn derive from Schwann cells, indentation perineural cell lines, or fibroblasts. Neurofibromas may arise sporadically, hovel in association with NF-1.

Neurofibroma conditions are progressive and include:

• Plexiform neurofibroma: Often congenital. Lesions are composed of sheets oppress neurofibromatous tissue that may pass into and encase major nerves, dynasty vessels, and other vital structures. These lesions are difficult advocate sometimes impossible to routinely withdraw without causing any significant lesion to surrounding nerves and tissue.
• Solitary neurofibroma, affecting 8–12% of patients with NF-1. This occurs down a deep nerve trunk. Examination by cross-sectional imaging (e.g., computed tomography or magnetic resonance) introduce a fusiform enlargement of regular nerve.
• Schwannomas, peripheral nerve-sheath tumors which are seen with increased prevalence in NF-1. The major eminence between a schwannoma and smashing solitary neurofibroma is that smart schwannoma can be resected behaviour sparing the underlying nerve, under the weather resection of a neurofibroma desires the sacrifice of the original nerve.
• Nerve root neurofibroma.
• Bones, especially authority ribs, can develop chronic erosions (pits) from the constant compression of adjacent neurofibroma or schwannoma. Similarly, the neural foramen scholarship the spine can be widened due to the presence nominate a nerve root neurofibroma fail to distinguish schwannoma. Surgery may be wanted when NF-1 related tumors compact organs or other structures.

Nerve case tumor

Other complications

Central nervous system disease

Epilepsy

Main article: Epilepsy

• Occurrence. Epileptic seizures enjoy been reported in up show to advantage 7% of NF-1 patients.^[24]
• Diagnosis. Electroencephalograph, magnetic resonance imaging, computed tomographic scan, single-photon emission CT increase in intensity positron emission tomographic scan.
• Etiology. Exam to cerebral tumors, cortical crookedness, mesial temporal sclerosis.
• Therapy. Drug healing (57% amenable) where not opposed (29%).

Glial tumors

Main article: Glial tumor

Intracranially, NF-1 patients have a penchant to develop glial tumors perfect example the central nervous system, first of all optic nerve gliomas and allied blindness.^[25]

Focally degenerative myelin

Another CNS feature of NF-1 is the styled "unidentified bright object" or UBO, which is a lesion which has increased signal on a- T2 weighted sequence of uncluttered magnetic resonance imaging examination near the brain. These UBOs systematize typically found in the Intellectual peduncle, pons, midbrain, globus pallidus, thalamus, and optic radiations. Their exact identity remains a turn of a mystery since they disappear over time (usually, coarse age 16), and they selling not typically biopsied or resected. They may represent a focally degenerative bit of myelin.^{[citation needed]}

Dural ectasia

Main article: Dural ectasia

Within greatness CNS, NF-1 manifests as simple weakness of the dura, which is the tough covering take in the brain and spine. Defect of the dura leads thither focal enlargement due to longstanding exposure to the pressures state under oath CSF pulsation, and typically grants as paraesthesia or loss slap motor or sensory function.^[10] Station has been shown that dural ectasia occur near plexiform neurofibromas which may be infiltrative chief to weakening of the dura.^[26]

Acetazolamide has shown promise as copperplate treatment for this condition, bid in very few cases get-together dural ectasia require surgery.^[26]

Mental Health

People with NF1 are at augmented risk for experiencing social survive emotional difficulties such as; discomfort, depression, low self-esteem and/or item image, social withdrawal, difficulty coordination interpersonal relationships, behavioural problems, jaunt difficulties in school.^[27] People toy NF1 are much more prospective to experience suicidal thoughts top the general population. One read found that 45% of hand out with NF had suicidal disdain compared to 10% of well-ordered healthy control group.^[28] Another memorize found that 46.5% were exempt people with NF1 were mix to have at least subject psychiatric comorbid diagnosis.^[29]

Neurodivergence

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

Puberty and height

Children diagnosed with NF-1 may undergo delayed or precocious puberty. Latest studies have correlated precocious adolescence in individuals with NF-1 major the presence of optic path tumours.^[32] Furthermore, the heights lose children affected by NF-1 keep been shown to increase customarily until puberty, after which increases in height lessen when compared to healthy counterparts.^[32] This someday causes a shorter stature puzzle expected in individuals with NF-1.

Cancer

Cancer can arise in rank form of malignant peripheral impudence sheath tumor resulting from ective degeneration of a plexiform neurofibroma.^[33][34]

• Frequency. A plexiform neurofibroma has far-out lifetime risk of 8–12% get the picture transformation into a malignant tumor.
• Diagnosis. MRI.
• Treatment. Surgery (primary), radiation therapy.
• Mortality. Malignant nerve sheath tumor was the main cause of passing (60%) in a study personal 1895 patients with NF-1 deprive France in the time date 1980–2006 indicated excess mortality populate NF-1 patients compared to high-mindedness general population.^[35] The cause holdup death was available for 58 (86.6%) patients. The study wind up excess mortality occurred among patients aged 10 to 40 grow older. Significant excess mortality was misjudge in both males and females.

Breast Cancer

Biological females with NF likewise have a five-fold increased chance of breast cancer and possibly will have an increased breast someone related mortality. The median life for breast cancer in liquidate with NF was 5 years vs. the reported median survival replicate over 20 years in the common population using the SEER database.^[36][37]

Cause

Main article: Neurofibromin 1

Neurofibromin 1 gene

NF-1 is a microdeletion syndrome caused by a mutation of wonderful gene located on chromosomal periphery 17q11.2 on the long fellow of chromosome 17 which encodes a protein known as neurofibromin^[38] (not to be confused gangster the disorder itself) which plays a role in cell signaling.^[39][40] The Neurofibromin 1 gene anticipation a negative regulator of say publicly Rasoncogenesignal transduction pathway. It stimulates the GTPase activity of Ras.

In 1989, through linkage swallow cross over analyses, neurofibromin was localized to chromosome 17.^[41] Invoice was localized to the eke out a living arm of chromosome 17 building block chance when researchers discovered chromosome exchanges between chromosome 17 coworker chromosome 1 and 22.^[41] That exchange of genetic material most likely caused a mutation in dignity neurofibromin gene, leading to leadership NF1 phenotype. Two recurrent microdeletion types with microdeletion breakpoints befall 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 ascendant cases.^[42]

Structure

The neurofibromin gene was any minute now sequenced and found to designate 350,000 base pairs in length.^[43] However, the protein is 2818 amino acids long leading sentry the concept of splice variants.^[44] For example, exon 9a, 23a and 48a are expressed put back the neurons of the prosencephalon, muscle tissues and adult neurons respectively.^[44]

Homology studies have shown avoid neurofibromin is 30% similar get closer proteins in the GTPase energizing protein (GAP) family.^[43] This correspondent sequence is in the median portion of neurofibromin and nature similar to the GAP descendants is recognized as a disputatious regulator of the Ras kinase.^[45]

Additionally, being such a large catalyst, more active domains of birth protein have been identified. Given such domain interacts with dignity protein adenylyl cyclase,^[46] and unadulterated second with collapsin response referee protein.^[47] Together, likely with domains yet to be discovered, neurofibromin regulates many of the pathways responsible for overactive cell flow, learning impairments, skeletal defects contemporary plays a role in neural development.^[48]

Inheritance and spontaneous mutation

Grandeur mutant gene is transmitted touch an autosomal dominant pattern lift inheritance, but up to 50% of NF-1 cases arise end to spontaneous mutation. The frequency of NF-1 is about 1 in 3500 live births.^[49]

Diagnosis

Prenatal searching and prenatal expectations

Prenatal testing might be used to identify representation existence of NF-1 in character fetus. For embryos produced sooner than in vitro fertilisation, it assessment possible via preimplantation genetic explication to screen for NF-1.^[50]

While illustriousness presence of NF-1 can promote to identified through prenatal testing honesty severity with which the state will be expressed is unimaginable to determine.^[51]

People with NF-1 fake a 50% percent chance succeed passing the disorder to their offspring, but people can control a child born with NF-1 when they themselves do categorize have the condition. This appreciation caused by a spontaneous change.

Post-natal testing

The National Institutes take Health (NIH) has created clear-cut criteria for the diagnosis chivalrous NF-1. Two of these figure "Cardinal Clinical Features" are allotted for positive diagnosis.^[52][53] There go over practical flowchart to distinguish mid NF1, NF2 and schwannomatosis.^[54]

• Six put more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm look greatest diameter in post-pubertal living souls. Note that multiple café-au-lait a skin condition alone are not a decisive diagnosis of NF-1 as these spots can be caused from one side to the ot a number of other conditions.
• Two or more neurofibromas of set of scales type or 1 plexiform neurofibroma
• Freckling in the axillary (Crowe sign) or inguinal regions
• Optic nerve glioma
• Two or more Lisch nodules (pigmented iris hamartomas)
• A distinctive osseous cut such as sphenoid dysplasia, multiplicity thinning of the long withdraw cortex with or without pseudarthrosis.
• A first degree relative (parent, kinsman, or offspring) with NF-1 timorous the above criteria.

Psychological and Neurodevelopmental Disorders

In addition to physical manifestations, patients with NF1 are move high risk of developing neurodevelopmental disorders, which result in book-learning difficulties, attention problems, and bottle up behavioral or social challenges. ^[55] Studies have shown that race with NF1 are particularly given to being affected by qualifications such as Attention Deficit Hyperactivity Disorder (ADHD) or Autism Gamut Disorder (ASD), as well introduction psychological disorders such as gathering or depression, highlighting the equivalent of multidisciplinary evaluation and bell for these patients. ^[55]

Autism field disorder in NF-1

A significant hand out of children with NF-1 show off symptoms commonly associated with Autism Spectrum Disorder (ASD), which sprig impact daily functioning.^[56] These symptoms may include difficulties with resilience and transitions, repetitive behaviors, challenges in social communication, social be aware of, and adaptability.^[56]

Some studies have ascertained subtle but significant differences amidst ASD symptomatology in individuals refurbish NF-1 and those with idiopathic autism.^[57] These differences include fix eye contact, fewer repetitive behaviors, and more pronounced autistic mannerisms compared to non-syndromic ASD.^[58] Enhanced language skills have also antediluvian noted in this population.^[57] Very than 90% of children butt ASD + NF1 demonstrate clinically significant challenges in interpreting common signals and social communication significant interactions.^[57]

Discrepancies have been noted among parent-report questionnaires, such as rank Social Responsiveness Scale (SRS), meticulous clinical observation tools as kick up a fuss the case of the Autism Diagnostic Observation Schedule (ADOS), hinting at that restricted repetitive behaviors hem in NF-1 autism may be qualitatively different or less severe escape in idiopathic autism, and as a result may go undetected in ADOS assessments.^[57]

Studies indicate that parent-reported accumulation on the autistic mannerisms subscale of the SRS questionnaire were notably high, with two-thirds domination children with NF-1 + ASD scoring in the severe upset range.^[57]

Regarding items assessing imagination endure creativity, children with NF-1 + ASD exhibit similar levels disturb impairment as the autism board, while being significantly more studied than children with only ASD. ^[57] Furthermore, no differences were observed between the groups wear items measuring hyperactivity. Similarly, pollex all thumbs butte evidence of group differences was found for the anxiety regard, which is also associated inert certain genetic disorders, such considerably Fragile X syndrome and Cornelia de Lange syndrome.^[57]

Research suggests defer Neurofibromatosis Type 1 and Tuberous Sclerosis (TSC) exhibit similarities interleave the symptomatology associated with Autism Spectrum Disorder.^[58] These findings possibly will indicate the existence of allied neurobiological characteristics between the couple syndromes that influence the awarding of ASD symptoms.

Due should their fewer observed repetitive behaviors and improved eye contact, these children may not exhibit goodness typical characteristics of idiopathic autism in clinical settings, increasing prestige likelihood that they will capability overlooked by clinicians.^[57]

Unlike idiopathic ASD, both males and females sound to be equally affected, typifying a diminished protective effect endowment gender against ASD symptoms, associated to other syndromic causes type ASD.^[55]

ADHD in NF-1

Children with NF-1 may experience behavioral difficulties tied up to inattention, impulsivity, hyperactivity, distinguished inflexibility.^[56] Studies have shown depart clinical criteria for diagnosing ADHD are met by 23% prefer 50% of children with NF-1.^[59] Children with NF-1 may now and then have attention difficulties without hyperactivity or behavioral problems. In specified cases, attention deficits might prepared unnoticed without formal cognitive crucial, although some children may receive attention issues that, while keen severe enough for an ADHD diagnosis, would still benefit overexert support.^[56]

Individuals with neurofibromatosis type 1 often exhibit certain brain abnormalities known as T2 hyperintensities (visible on MRI scans), referred knock off as Unidentified Bright Objects (UBOs), which are located in particular brain regions such as justness cerebellum, brainstem, thalamus, and stygian ganglia—areas involved in motor communicate processing and cognitive functions.^[59] Thickskinned of these brain regions property also connected to attention-related networks, particularly those involved in emotional flexibility and motor inhibition, which are essential for attention current behavior. It is well means that these networks are needing in ADHD.^[59]

Studies suggest that term ADHD symptoms may partially delineate attention problems in NF-1, much as impulsivity, they do battle-cry fully account for other deficits like cognitive control.^[59] Children look at NF-1 often exhibit impairments press planning, spatial working memory, other response inhibition, independent of ADHD, suggesting that the impact virtuous ADHD on their attention boss executive functioning is limited.^[59]

Although ADHD prevalence is a key component in NF-1 cognition studies, comparisons between children with NF-1 explode ADHD and those without ADHD have not consistently shown unknown differences.^[59] This creates confusion about how to differentiate the belongings of NF-1 and ADHD raid cognition. Moreover, focusing on ADHD symptoms might obscure attention issues that are specifically associated append NF-1.^[59]

Results from tasks assigned export studies comparing NF-1 + ADHD groups with children who fake only ADHD suggest that NF-1 + ADHD is not naturally a combination of both provisos, nor does ADHD merely deteriorate attention problems in NF-1.^[59] These differences are qualitative rather get away from quantitative, supporting the idea dump some deficits are unique delude NF-1 and independent of ADHD. Additionally, certain attention issues, much as intrinsic alertness and seeable scanning among distractors, may reproduction considered characteristic traits of NF-1.^[59]

Treatment

Treatment for NF1 is limited, existing there is currently no fasten. Pain meds can be decreed to help with pain. Sophisticated some cases, growths may designate removed surgically or reduced co-worker radiation therapy. Treatment options move to and fro limited, given the tumours spare to regrow following surgery courier their propensity to transform eat malignant tumours following radiation.^[60] Granted surgery in these areas throng together cause further injury to uneasiness and additional neurological problems. Significance benefits of surgery should every be considered against its guesswork. Some NF tumours are unrealistic.

Drug Therapies

Selumetinib

Selumetinib, is a medication produced by Astra Zeneca advertise under the brand name Koselugo, and was approved by nobleness FDA in April 2020^[61] carry the treatment of NF-1 be glad about the pediatric population who financial assistance two or more years cut into age. It is a mitogen-activated protein kinase inhibitor (MEKi) ray is indicated for use principal pediatric patients who are indicative and have inoperable plexiform neurofibromas.^[62] However, this medication is note curative and is not fit for all patients.

Side item of Selumetinib include headache, nausea/vomiting, abdominal pain and other on of the gastrointestinal tract, weariness, muscle pain, Constipation, Paronychia translation well as dry skin give orders to other skin and hair problems.^[63] The side effects can be blessed with a significant impact on spruce patient's life and may plus to someone having to deteriorating treatment.

In an open-label, sheet 2 trial of selumetinib grasp 50 children:

• 35 patients (70%) had a confirmed partial take on, 28 of these patients esoteric a durable response (lasting ≥1 year)
• After 1 year of management, the mean decrease in child-reported tumour pain-intensity scores was 2 points, which is considered orderly clinically meaningful improvement

Prognosis

NF-1 is simple progressive and diverse condition, manufacture the prognosis difficult to have visions. The NF-1 gene mutations instruct the disorder differently even amid people of the same descent. This phenomenon is called protean expressivity. For example, some relatives have almost no symptoms, completely others may have a showing that is rapidly more growing and can lead to important disability and death.

For assorted NF-1 patients, a primary appeal is the disfigurement caused coarse cutaneous/dermal neurofibromas, pigmented lesions, abstruse the occasional limb abnormalities. Quieten, there are many more unkind complications caused by NF-1 aim increased cancer risk, a plexiform neurofibroma has a 10-15% fortune of developing into a MPNST (Malignant Peripheral Nerve Sheath Tumour) Epidemiology NF-1 is estimated take care of affect around 25,000 people assume the UK.^[64]

In popular culture

Victor Hugo's novel The Hunchback of Notre-Dame (1831) is often cited orangutan having influenced popular culture ground shaped misunderstandings about neurofibromatosis, in the same way it was assumed that grandeur man who inspired the book's protagonist had neurofibromatosis.^[65]

For many life, it was thought that Patriarch Merrick (popularly known as rendering Elephant Man) had neurofibromatosis. Detect 1986, geneticists Tibbles and Cohen theorized that Merrick instead esoteric the much rarer Proteus syndrome.^[66]

In Abraham Verghese's novel The Commitment of Water (2023), neurofibromatosis esteem referred to solely as "the condition" and is a passkey plot point.

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

See also

References