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<div class="noeditbox">Welcome to [[Pathophysiology of Complex Patient Problems|PT 635 Pathophysiology of Complex Patient Problems]] This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!</div><div class="editorbox">
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'''Original Editors '''-Nick Pucillo &amp; Cody Russell&nbsp;[[Pathophysiology of Complex Patient Problems|from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  
'''Original Editors '''-Nick Pucillo &amp; Cody Russell&nbsp;[[Pathophysiology of Complex Patient Problems|from Bellarmine University's&nbsp;Pathophysiology of Complex Patient Problems project.]]  


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'''Top Contributors''' - {{Special:Contributors/{{FULLPAGENAME}}}} &nbsp;  
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== Definition/Description  ==
== Introduction ==
[[File:CALM.jpg|thumb|Cafe-au-lait Macules]]
[[File:Lisch Nodule.jpg|thumb|Lisch Nodule]]Neurofibromatosis 1 (NF1) is characterized by multiple café au lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, and choroidal (vascular layer of the eye) freckling. About half of people with NF1 have plexiform neurofibromas, but most are internal and not suspected clinically. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include [[Optic Nerve|optic nerve]] and other central nervous system gliomas, malignant peripheral nerve sheath tumors, [[scoliosis]], [[Tibia|tibial]] dysplasia, and vasculopathy.<ref name=":1" />


Neurofibromatosis Type 1 (NF1) is an autosomal dominant disorder on the long arm of chromosome 17, characterized by predominately benign tumor growth on nerve sheathes called neurofibromas and cutaneous spotting called café-au-lait macules. The role of the mutated, naturally occurring protein neurofibromin is not fully understood but does appear to play some role in regulating Ras proteins which promote cell division and growth. NF1 varies a great deal in presentation and complications, even between immediate family members.<ref name="Julian" /><ref name="Genetics">Genetics Home Reference. Neurofibromatosis type 1. Available at: http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1. Accessed March 4, 2014].</ref>  
* It is an [[Genetic Conditions and Inheritance|autosomal dominant disorder]] on the long arm of chromosome 17. NF1 varies a great deal in presentation and complications, even between immediate family members.<ref name=":0">medline plus NF1 Available: https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1/<nowiki/>(accessed 6.3.2022)</ref><ref name="Julian">Julian N, Edwards NE, DeCrane S, Hingtgen CM. Neurofibromatosis 1: Diagnosis and Management. The Journal for Nurse Practitioners. 2014;10(1):30-35.</ref><ref name="Genetics">Genetics Home Reference. Neurofibromatosis type 1. Available at: http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1. Accessed March 4, 2014].</ref>
* Neruofibromatosis type 1 affects approximately 1 in 3,000 peolple worldwide.&nbsp; Neruofibromatosis occurs equally between sexes and races.<ref name="Ortho">Feldman DS, Jordan C, Fonseca L. Orthopaedic manifestations of neurofibromatosis type 1. J Am Acad Orthop Surg. 2010;18(6):346-57.</ref>
* The median life expectancy of individuals with NF1 is approximately eight years lower than in the general population. Malignancy (especially malignant peripheral nerve sheath tumors) and vasculopathy are the most important causes of early death in individuals with NF1.<ref name=":1">Friedman JM. Neurofibromatosis 1. 1998 Oct 2 [Updated 2019 Jun 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1109/ (accessed 6.3.2022)</ref>
This is a good 2 minute video on NF1{{#ev:youtube|BQBKQB3zq9s}}<ref>Neurofibromatosis. Available at:http://www.youtube.com/watch?v=BQBKQB3zq9s</ref>


<br>
== Characteristics/Clinical Presentation ==
[[Image:Neruofibroma.jpg|frame|Neurofibroma|alt=]]Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots, These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.
[[File:NeurofibromatosisGlioma.jpg|thumb|Neurofibromatosis Glioma]]
Most adults with neurofibromatosis type 1 develop neurofibromas, which are benign tumors that are usually located on/just under the skin.


== Prevalence  ==
# They may also occur in nerves near the [[Spinal cord anatomy|spinal cord]] or along nerves elsewhere in the body.
# Some people with neurofibromatosis type 1 develop malignant peripheral nerve sheath tumors that grow along nerves, usually developing in adolescence or adulthood.
# People with neurofibromatosis type 1 also have an increased risk of developing other [[Oncology|cancers]], including [[Brain Tumors|brain tumors]] and [[leukemia]].
# During childhood, benign growths (Lisch nodules) often appear in the colored part of the iris), they do not interfere with vision.
# Some with NF1 also develop tumors that grow along the optic nerve (optic gliomas), which may lead to no loss all the way to total vision loss.<ref name=":0" />


Neruofibromatosis type 1 affects approximately 1 in 3,000 peolple worldwide.&nbsp; Neruofibromatosis occurs equally between sexes and races.<ref name="Ortho" />  
Additional signs and symptoms of neurofibromatosis type 1 vary, can include [[hypertension]], short stature, an unusually large head (macrocephaly), and skeletal abnormalities eg scoliosis. Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and [[Attention Deficit Disorders|attention-deficit]]/hyperactivity disorder (ADHD) occur frequently in affected individuals<ref name=":0" />.
*
== Diagnosis ==


== Characteristics/Clinical Presentation<br> ==
The diagnosis of NF1 is usually based on clinical findings. Molecular genetic testing of NF1 is rarely needed for diagnosis.<ref name=":1" />
 
Neurofibromatosis type 1 has dermal, ocular, neoplastic, neurological, cardiovascular, and orthopedic manifestations.&nbsp; These various manifestations are what calls for aggressive treatment from a multidisciplinary team. <br>
 
[[Image:NFbody.jpg|thumb|center|379x442px|Clinical Presentation of NF1]]
 
<u>'''Dermal Manifestations'''</u>
 
*&nbsp;Cafe-au-lait macules (CALM): CALM is one of the most prevalent features of NF1.&nbsp; These macules are usually on of the first features to present in patients.&nbsp; These lesions are flat along the patient's skin and have a coffee-colored hyperpigmentation.&nbsp; The lesions are also round with well-defined borders and have an average diameter of 2-5 cm. <ref name="Ortho" />CALM is one of the cardinal diagnostic criteria for NF1.&nbsp; When multiple macules are present, NF1 is highly suggestive.&nbsp;<ref name="Boyd">Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61(1):1-14.</ref><br>
 
[[Image:CALM.jpg|frame|center|Cafe-au-lait Macules]]
 
*Skin Fold Freckling: Skin fold freckling are little brown macules that appear in regions where freckling is uncommon.&nbsp; These areas include the axilla, inguinal region, breast folds, neck, and upper eyelids. <ref name="Ortho" />Skin fold freckling is also involved in the diagnostic criteria for NF1 and usually occurs around the ages of 3 to 5 years.&nbsp;<ref name="Boyd" />
 
<u>'''Ocular/Orbital Manifestations'''</u>
 
*Lisch Nodules: Lisch nodules are hyperpigmentations of the iris.&nbsp; The hamartomas are affected consisting of a spindle-shaped cells.&nbsp; Lisch nodules do not cause visual impairments. <ref name="Ortho" />Visualization requires slit lamp examination by experienced practitioner.&nbsp; Eye examination is necessary in individuals in which the diagnosis of NF1 is uncertain. <ref name="Boyd" />
 
[[Image:Lisch Nodule.jpg|frame|center|Lisch Nodule]]
 
*Optic Pathway Glioma (OPGs): OPG is a tumor of the optic nerve and is present in 15% to 20% of NF1 patients.&nbsp; The tumor is slow growing and clinically presents as eye proptosis, decreased visual acuity, or precious puberty.&nbsp; Symptoms usually present before the age of 6 with diagnosis made by 3 years of age. <ref name="Boyd" />
 
[[Image:NeurofibromatosisGlioma.jpg|frame|center|Optic Pathway Glioma]]
 
<u>'''Neoplastic Manifestaions'''</u>
 
*Neuofibroma: Neuorfibromas are benign neoplasms of peripheral nerve sheaths.&nbsp; They are composed of schwann cells, fibroblast, perineural cells, and mast cells.&nbsp; Neurofibromas typically evolve in late childhood.&nbsp; Nerofibromas can increase in both size and magnitude with time with periods of accelerated proliferation during puberty and pregnancy. <ref name="Ortho" />Neuofibromas are a hallmark sign of NF1 and present as dome-shaped, soft, fleshy, slightly hyperpigmentated cutaneous tumors.&nbsp; Subcutaneous neruofibromas present as firm and nodular.&nbsp; <ref name="Boyd" /><br>
 
[[Image:Neruofibroma.jpg|frame|center|Neurofibroma]]
 
*Plexiform Neurofibroma (PN): The plexiform neuorbifroma differs from cutaneous neruofibroma in that PN is usually congenital. PNs present as hyperpigmentated and/or hypertrichosis tumors and can develop into malignant peripheral nerve sheath tumors.&nbsp;<ref name="Boyd" />
*Malignancies: Individuals with NF1 are at a greater risk of developing benign and malignant neoplasms.&nbsp; These neoplasms include melanoma, leukemia, rhabdomyosarcoma, pheochromocytoma, carcinoma, and pancreatic endocrine tumors. <ref name="Ortho" />
 
<u>'''Neurologic Manifestations'''</u>
 
*Learning Disability: 75% of NF1 children have some sort of learning disability.&nbsp; Speech and language deficits have been noted along with delayed gross motor development. <ref name="Ortho" />Frequent assessments must be made for developmental milestone delays, learning disabilities, and school performances.&nbsp; <ref name="Boyd" />
 
<u>'''Cardiovascular Manifestations'''</u>
 
*Individuals with NF1 are at a greater risk for stroke, hypertension, congenital heart disease, and vasculopathy. <ref name="Ortho" />
 
<u>'''Orthopaedic Manifestations'''</u>
 
*Spinal Deformity: Spinal deformity is common in NF1 and is thought to be caused by osteomalacia, intraspinal neruofibromas that erode and infiltrate bone, and endocrine disturbances.&nbsp; Several dystropic changes in NF1 are rib penciling, vertebral scalloping, dumbbell lesions, and dural ectasia.&nbsp; Less common Dystropic changes are spindling of the transverse process, vertebral wedging and rotation, foraminal enlargement, widened interpediculate distance, and dysplasia of the pedicles. <ref name="Ortho" />
*Scoliosis: The most common orthopedic finding in NF1 patient's is scoliosis and usually manifests around 10 years of age.&nbsp; The pathogenesis of scoliosis is uncertain but may be related to osteopenia and subsequent dysplasic bones. <ref name="Boyd" />Individuals with NF1 will require regular scoliosis screenings and should be evaluated with MRI or CT scans for accurate assessment of the deformity.&nbsp; Management of the scoliosis is based primarily on the degrees of the curvature of the spine.&nbsp;<ref name="Ortho" />
*Long Bone Dysplasias: The most commonly affected long bone in individuals with NF1 is the tibia.&nbsp; The tibia will typically bow in an anterior-lateral direction.&nbsp; Overgrowth or congenital pseudoarthrosis are common dysplasias of NF1.&nbsp; These dysplasias produce abnormalities in fracture healing.&nbsp;<ref name="Boyd" /> Deformities in NF1 typically involve cortical thickening with a narrowed medullary canal.&nbsp;<ref name="Ortho" />
 
== Associated Co-morbidities  ==
 
Associated psychiatirc morbidity have been reported with NF1.&nbsp; Autism spectrum disorder and attention-deficit-hyperactivity disorder have shown to have a high prevalence with individuals with Neruofibramatosis type 1. <ref name="Garg">Garg S, Lehtonen A, Huson SM, et al. Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study. Dev Med Child Neurol. 2013;55(2):139-45.</ref>&nbsp; Hypertension is also significantly associated with NF1.&nbsp; The leading cause of hypertensions in NF1 patients is due to the stenosis of the renal arteries which decrease blood flow to the kidneys.<ref name="Cardio" />
 
== Medications  ==
 
The following is a list depicting common medications prescribed addressing signs/symptoms of Neruofibromatosis Type 1:<ref name="emed" />
 
*<u>Antihistamines</u>: Diphenhydramine (Benadryl, Benylin, Diphen, AllerMax)- May control itching by blocking effects of histamine
*<u>Alpha-adrenergic blocking agents</u>: Prazosin (Minipress), Doxazosin (Cardura)- Cause vasodilation of veins and arterioles and decrease total peripheral resistance and blood pressure
*<u>Antineoplastic agents</u>: Erlotinib (Tarceva), Sorafenib (Nexavar), Carboplatin (Paraplatin)- Inhibit cell growth and proliferation
 
<br>
 
== Diagnostic Tests/Lab Tests/Lab Values  ==
 
Neruofibromatosis type 1 is diagnosed through clinical assessment including patient history and physical examination.&nbsp; The National Institutes of Health have developed a diagnostic criteria for NF1 based upon common clinical features.&nbsp; The diagnosis is made by an individual having 2 or more of the following features:<br>
 
*Six or more cafe au laite macules &gt; 5 mm in prepubertal individuals and &gt; 15 mm in diameter in adults.
*Two or more neruorfibromas.
*Freckling in the axillary or inguinal regions.
*Optic glioma visual pathways tumors most often presenting as grade I pilocytic astrocytomas.
*Two or more Lisch Nodules
*Abnormal development of the spine (scoliosis), the sphenoid bone, or the tibia.
*A first degree relative with NF1
 
<br>
 
Early diagnosis is challenging because of the variable characteristics of NF1.<ref name="Julian">Julian N, Edwards NE, DeCrane S, Hingtgen CM. Neurofibromatosis 1: Diagnosis and Management. The Journal for Nurse Practitioners. 2014;10(1):30-35.</ref>&nbsp; Diagnosis my be delayed due to the different ages that features can emerge. <ref name="Ortho">Feldman DS, Jordan C, Fonseca L. Orthopaedic manifestations of neurofibromatosis type 1. J Am Acad Orthop Surg. 2010;18(6):346-57.</ref>


== Etiology/Causes  ==
== Etiology/Causes  ==


The genetic disorder that is Neruofibromatosis Type 1 originates from the NF1 gene that is located in the long arm of chromosome 17. While the role of the NF1 gene is not fully understood, it is known, however, that it produces the protein product neurofibromin. Neurofibromin indirectly dictates cell growth and division, at especially high levels in the nervous system (predominately as a suppressor). In individuals with Neurofibromatosis Type 1, neurofibromin is not produced in sufficient quantities to inhibit cell growth and thus, neruofibromas form along the nerves. While predominately all neuromas of Neurofibromatosis Type 1 are benign, there is a rare occasion in which a neuroma may be malignant (8-13%, especially so in 20-35 year olds). <ref name="Julian" /><ref name="Ferner">Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81-8.</ref>
[[Image:Genetic_Inheritance.jpg|frame|Autosomal Dominance Genetic Transmission|alt=]]
 
 
 
[[Image:Genetic_Inheritance.jpg|frame|center|Autosomal Dominance Genetic Transmission]]
 
== Systemic Involvement  ==
 
'''Musculoskeletal: '''Children with NF1 have been shown to have significantly lower motor proficiency than there peers without NF1. NF1 patients also have spinal malalignments resulting in scoliosis and a tendency to have long bone bowing in such bones as the tibia.'''&nbsp;''' <ref name="Motor">Johnson BA, Macwilliams BA, Carey JC, Viskochil DH, D'astous JL, Stevenson DA. Motor proficiency in children with neurofibromatosis type 1. Pediatr Phys Ther. 2010;22(4):344-8.</ref><ref name="Ortho" /><br>
 
'''Dermatological: '''Patient's with NF1 may develop a variety of cutaneous finding. Cafe-au-lait macules, Nerofibromas, skin freckling are all physical presentations associated with NF1. Other cutaneous findings include juvenile xanthogranuloma, glomus tumor, melanoma, nevus anemicus, and Pruritus.&nbsp; <ref name="Boyd" />
 
'''Vision:&nbsp; '''The presentation of Lisch Nodules and Optic Gliomas may have an affect on NF1 patient's vision. Individuals with Optic Gliomas may present with eye proptosis, decreased visual acuity, nystagmus, and optic disk atrophy.&nbsp;&nbsp;<ref name="Boyd" /><ref name="Ortho" />
 
'''Cardiovascular:&nbsp; '''Individuals with NF1 could have cardiovascular manifestations such as congenital heart disease, vasculopathy, and hypertension. Heart disease occurs at a higher than expected rate than the general public. Vasculopathies include stenosis, aneurysms, and arteriovenous malformations. High blood pressure is significantly associated with NF1. The most common cause of hypertension in the pediatric population is stenosis of the renal arteries. Blood pressure should be monitored annually.<ref name="Cardio">Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123(1):124-33.</ref>
 
'''Cognitive:&nbsp; '''Learning disabilities occur in NF1 patients. Children with NF1 have had noted delays in speech and language as well as motor development. There is a proposed relationship between unidentified bright objects on MRI and cognitive function but researchers are unsure of their clinical significance.&nbsp;&nbsp;&nbsp;<ref name="Boyd" /><ref name="Ortho" />
 
== Medical Management (current best evidence)  ==
 
Currently there is no treatment for the underlying cause of Neurofibromatosis Type 1. While several drugs have been administered and tried for both addressing etiology and symptoms, there have been few proven to have substantial benefits. Diphenhydramine (Benadryl, Benylin, Diphen, AllerMax) has been shown to give most comfort and relief for unceasing itching. Research trials continue in hopes for finding a cure, however, best medical management currently involves routine examinations by a team of health care clinicians. <ref name="Julian" /><ref name="emed">emedicine.com. Accessed March 4, 2014].</ref><ref name="Rosa">Rosalie E Ferner. Neurofibromatosis 1. European Journal of Human Genetics. 2006;15(2):131.</ref>
 
== Physical Therapy Management (current best evidence)  ==
 
*Best practice of physical therapy in individuals with NF1 has not been identified in research. Recognizing and treating impairments that manifest due to the underlying pathology is within our scope and should be considered when evaluating and treating a patient with NF1. <br>
*As a profession it is important to recognize the manifestations and diagnostic criteria of NF1 in order to screen appropriately regarding orthopedic, neurological, cardiovascular, integumentary, and cognitive impairments.<br>
*A series of case reports have been published depicting the benefits of strength training, stretching, postural training, and palliative medicine. <ref>Johnson BA, Salzberg CL, Stevenson DA. Effects of a plyometric training program for 3 children with neurofibromatosis type 1. Pediatr Phys Ther. 2012;24(2):199-208.</ref> <ref>Helmers KM, Irwin KE. Physical therapy as conservative management for cervical pain and headaches in an adolescent with neurofibromatosis type 1: a case study. J Neurol Phys Ther. 2009;33(4):212-23.</ref><br>
 
== Alternative/Holistic Management (current best evidence)  ==
 
'''Bee Propolis''':&nbsp; Studies have show effectiveness of bee propolis in stopping tumor growth.&nbsp; Propolis is a yellow-brown substance collected by worker honeybees from growing trees and shrubs.&nbsp; Caffeic acid phenethyl ester (CAPE) based proplis is used to stop NF1 tumor growth.&nbsp; NF1 tumors require the kinase PAK1 for their growth.&nbsp; CAPE-based propolis can block this kinase and suppress NF1 tumors completely suggesting that Bee propolis can be used as and effective therapeutic medicine.&nbsp; <ref>Farooqui T, Farooqui AA. Oxidative Stress in Vertebrates and Invertebrates, Molecular Aspects of Cell Signaling. John Wiley &amp;amp;amp;amp;amp; Sons; 2011.</ref>&nbsp;<ref>Demestre M, Messerli SM, Celli N, et al. CAPE (caffeic acid phenethyl ester)-based propolis extract (Bio 30) suppresses the growth of human neurofibromatosis (NF) tumor xenografts in mice. Phytother Res. 2009;23(2):226-30.</ref>
 
[[Image:Bee propolis.jpg|frame|center|600x600px|Bee Propolis (CAPE)]]<br>
 
'''Acupuncture''': Acupuncture can be used to alleviate some of the pain associated with NF1. <ref name="JHM">Comprehensive Neurofibromatosis (NF) Center. John Hopkins Medicine Website. Available at: http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/neurofibromatosis/. Accessed March 22, 2014.</ref> <br>
 
== Differential Diagnosis  ==
 
Following is a comprehensive list of diagnosis that potential mimic NF1:<ref name="Ferner" />


Other forms of neurofibromatosis <br>• Segmental/mosaic NF1 (http://www.nfauk.org/assets/downloads/SEGMENTAL%20NF1%20June%202011-6.pdf) <br>• Watson syndrome (http://rarediseases.info.nih.gov/gard/5540/watson-syndrome/resources/1)<br>• Autosomal dominant multiple café au lait patches alone (some allelic with NF1) (http://escholarship.org/uc/item/3d56c2q8)<br>• Neurofibromatosis 2 (http://www.physio-pedia.com/Neurofibromatosis_Type_II) <br>• Schwannomatosis (http://www.ctf.org/Learn-About-NF/Schwannomatosis.html)
The genetic disorder that is Neruofibromatosis Type 1 originates from the NF1 gene that is located in the long arm of chromosome 17. While the role of the NF1 gene is not fully understood, it is known, however, that it produces the protein product neurofibromin. Neurofibromin indirectly dictates cell growth and division, at especially high levels in the nervous system (predominately as a suppressor). In individuals with Neurofibromatosis Type 1, neurofibromin is not produced in sufficient quantities to inhibit cell growth and thus, neruofibromas form along the nerves. While predominately all neuromas of Neurofibromatosis Type 1 are benign, there is a rare occasion in which a neuroma may be malignant (8-13%, especially so in 20-35 year olds). <ref name="Julian" /><ref name="Ferner">Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81-8.</ref>
== Management ==


<br>Other conditions with café au lait patches<br>• McCune–Albright syndrome (http://ghr.nlm.nih.gov/condition/mccune-albright-syndrome) <br>• DNA repair syndromes (http://www.geneskin.org/dna-repair-disorders.aspx)<br>• Homozygosity for one of the genes causing hereditary non‐polyposis cancer of the colon. (http://www.ncbi.nlm.nih.gov/books/NBK1211/)
The usual treatment approach for any tumors associated with NF1 is to watch the person closely for signs of tumor growth or whether the person is having such symptoms as pain or weakness ie active surveillance.


<br>Conditions with pigmented macules confused with NF1<br>• LEOPARD syndrome (http://ghr.nlm.nih.gov/condition/multiple-lentigines-syndrome)<br>• Neurocutaneous melanosis (http://www.ncbi.nlm.nih.gov/pubmed/1869648) <br>• Peutz–Jeghers syndrome (http://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome)<br>• Piebaldism (http://ghr.nlm.nih.gov/condition/piebaldism)
* If symptoms develop over time, then surgery may be done to remove the tumor(s). It is usually possible to remove a tumor growing on or from nerves, and to preserve the nerve involved, unless it is a plexiform tumor (more spread out and often get into the nerve).  
* A cancerous tumor may be treated with cancer medications, radiation therapy, or a combination of treatments.  
* Clinical trials, meaning research studies, for neurofibromatosis are ongoing and currently focus on targeted therapy drugs that affect the ras signaling pathway inside the tumor cell.<ref>Cancer net NF1 Available: https://www.cancer.net/cancer-types/neurofibromatosis-type-1 (accessed 6.3.2022)</ref>


<br>Localized overgrowth syndromes<br>• Klippel–Trenauny–Weber syndrome (http://ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome)<br>• Proteus syndrome (http://ghr.nlm.nih.gov/condition/proteus-syndrome)
== Physical Therapy Management ==


<br>Conditions causing tumors confused with neurofibromas<br>• Lipomatosis (http://www.pathologyoutlines.com/topic/softtissueadiposelipomatosis.html)<br>• Banayan–Riley–Ruvalcuba syndrome (http://ghr.nlm.nih.gov/condition/bannayan-riley-ruvalcaba-syndrome)<br>• Fibromatoses (http://rarediseases.info.nih.gov/gard/6439/fibromatosis/resources/1) <br>• Multiple endocrine neoplasia type 2B (http://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia) <br>
*Best practice of physical therapy in individuals with NF1 has not been identified in research. Recognizing and treating impairments that manifest due to the underlying pathology is within our scope and should be considered when evaluating and treating a patient with NF1. <br>
*As a profession it is important to recognize the manifestations and diagnostic criteria of NF1 in order to screen appropriately regarding orthopedic, neurological, cardiovascular, integumentary, and cognitive impairments.<br>
*A series of case reports have been published depicting the benefits of strength training, stretching, postural training, and palliative medicine. <ref>Johnson BA, Salzberg CL, Stevenson DA. Effects of a plyometric training program for 3 children with neurofibromatosis type 1. Pediatr Phys Ther. 2012;24(2):199-208.</ref> <ref>Helmers KM, Irwin KE. Physical therapy as conservative management for cervical pain and headaches in an adolescent with neurofibromatosis type 1: a case study. J Neurol Phys Ther. 2009;33(4):212-23.</ref>


== Case Reports/ Case Studies  ==
== Case Reports/ Case Studies  ==


Physical therapy as conservative management for cervical pain and headaches in an adolescent with neurofibromatosis type 1: a case study.<br>
Physical therapy as conservative management for cervical pain and headaches in an adolescent with neurofibromatosis type 1: a case study: [http://www.ncbi.nlm.nih.gov/pubmed/20208466 www.ncbi.nlm.nih.gov/pubmed/20208466]<br>
 
[http://www.ncbi.nlm.nih.gov/pubmed/20208466 www.ncbi.nlm.nih.gov/pubmed/20208466]<br>
 
Effects of a plyometric training program for 3 children with neurofibromatosis type 1.<br>
 
[http://www.ncbi.nlm.nih.gov/pubmed/22466394 www.ncbi.nlm.nih.gov/pubmed/22466394]<br>
 
 
 
add links to case studies here (case studies should be added on new pages using the [[Template:Case Study|case study template]])<br>
 
== Resources <br>  ==
 
{{#ev:youtube|BQBKQB3zq9s}}&nbsp;<ref>Neurofibromatosis. Available at:http://www.youtube.com/watch?v=BQBKQB3zq9s</ref>
 
http://www.nfnetwork.org/
 
http://nfincne.org/<br>
 
http://www.nfmidwest.org/<br>
 
http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/neurofibromatosis/nf1/<br>


== Recent Related Research (from [http://www.ncbi.nlm.nih.gov/pubmed/ Pubmed])  ==
Effects of a plyometric training program for 3 children with neurofibromatosis type 1.: [http://www.ncbi.nlm.nih.gov/pubmed/22466394 www.ncbi.nlm.nih.gov/pubmed/22466394]<br>
<div class="researchbox">
<rss>http://www.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1R__6bbhMkewq1OMIhABVLHf5ZmSNoI32HN5hB0oHpBy2-81KU|charset=UTF-8|short|max=10</rss>
</div>


== References  ==
== References  ==
see [[Adding References|adding references tutorial]].


<references />&nbsp;  
<references />&nbsp;  


[[Category:Bellarmine_Student_Project]]
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Latest revision as of 02:29, 6 March 2022

Original Editors -Nick Pucillo & Cody Russell from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Nicholas Pucillo, Cody Russell, Lucinda hampton, Elaine Lonnemann, WikiSysop, Wendy Walker, Kim Jackson and Shaimaa Eldib  

Introduction[edit | edit source]

Cafe-au-lait Macules
Lisch Nodule

Neurofibromatosis 1 (NF1) is characterized by multiple café au lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, and choroidal (vascular layer of the eye) freckling. About half of people with NF1 have plexiform neurofibromas, but most are internal and not suspected clinically. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy.[1]

  • It is an autosomal dominant disorder on the long arm of chromosome 17. NF1 varies a great deal in presentation and complications, even between immediate family members.[2][3][4]
  • Neruofibromatosis type 1 affects approximately 1 in 3,000 peolple worldwide.  Neruofibromatosis occurs equally between sexes and races.[5]
  • The median life expectancy of individuals with NF1 is approximately eight years lower than in the general population. Malignancy (especially malignant peripheral nerve sheath tumors) and vasculopathy are the most important causes of early death in individuals with NF1.[1]

This is a good 2 minute video on NF1

[6]

Characteristics/Clinical Presentation[edit | edit source]

Neurofibroma

Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots, These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.

Neurofibromatosis Glioma

Most adults with neurofibromatosis type 1 develop neurofibromas, which are benign tumors that are usually located on/just under the skin.

  1. They may also occur in nerves near the spinal cord or along nerves elsewhere in the body.
  2. Some people with neurofibromatosis type 1 develop malignant peripheral nerve sheath tumors that grow along nerves, usually developing in adolescence or adulthood.
  3. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and leukemia.
  4. During childhood, benign growths (Lisch nodules) often appear in the colored part of the iris), they do not interfere with vision.
  5. Some with NF1 also develop tumors that grow along the optic nerve (optic gliomas), which may lead to no loss all the way to total vision loss.[2]

Additional signs and symptoms of neurofibromatosis type 1 vary, can include hypertension, short stature, an unusually large head (macrocephaly), and skeletal abnormalities eg scoliosis. Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention-deficit/hyperactivity disorder (ADHD) occur frequently in affected individuals[2].

Diagnosis[edit | edit source]

The diagnosis of NF1 is usually based on clinical findings. Molecular genetic testing of NF1 is rarely needed for diagnosis.[1]

Etiology/Causes[edit | edit source]

Autosomal Dominance Genetic Transmission

The genetic disorder that is Neruofibromatosis Type 1 originates from the NF1 gene that is located in the long arm of chromosome 17. While the role of the NF1 gene is not fully understood, it is known, however, that it produces the protein product neurofibromin. Neurofibromin indirectly dictates cell growth and division, at especially high levels in the nervous system (predominately as a suppressor). In individuals with Neurofibromatosis Type 1, neurofibromin is not produced in sufficient quantities to inhibit cell growth and thus, neruofibromas form along the nerves. While predominately all neuromas of Neurofibromatosis Type 1 are benign, there is a rare occasion in which a neuroma may be malignant (8-13%, especially so in 20-35 year olds). [3][7]

Management[edit | edit source]

The usual treatment approach for any tumors associated with NF1 is to watch the person closely for signs of tumor growth or whether the person is having such symptoms as pain or weakness ie active surveillance.

  • If symptoms develop over time, then surgery may be done to remove the tumor(s). It is usually possible to remove a tumor growing on or from nerves, and to preserve the nerve involved, unless it is a plexiform tumor (more spread out and often get into the nerve).
  • A cancerous tumor may be treated with cancer medications, radiation therapy, or a combination of treatments.
  • Clinical trials, meaning research studies, for neurofibromatosis are ongoing and currently focus on targeted therapy drugs that affect the ras signaling pathway inside the tumor cell.[8]

Physical Therapy Management[edit | edit source]

  • Best practice of physical therapy in individuals with NF1 has not been identified in research. Recognizing and treating impairments that manifest due to the underlying pathology is within our scope and should be considered when evaluating and treating a patient with NF1.
  • As a profession it is important to recognize the manifestations and diagnostic criteria of NF1 in order to screen appropriately regarding orthopedic, neurological, cardiovascular, integumentary, and cognitive impairments.
  • A series of case reports have been published depicting the benefits of strength training, stretching, postural training, and palliative medicine. [9] [10]

Case Reports/ Case Studies[edit | edit source]

Physical therapy as conservative management for cervical pain and headaches in an adolescent with neurofibromatosis type 1: a case study: www.ncbi.nlm.nih.gov/pubmed/20208466

Effects of a plyometric training program for 3 children with neurofibromatosis type 1.: www.ncbi.nlm.nih.gov/pubmed/22466394

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 Friedman JM. Neurofibromatosis 1. 1998 Oct 2 [Updated 2019 Jun 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1109/ (accessed 6.3.2022)
  2. ↑ 2.0 2.1 2.2 medline plus NF1 Available: https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1/(accessed 6.3.2022)
  3. ↑ 3.0 3.1 Julian N, Edwards NE, DeCrane S, Hingtgen CM. Neurofibromatosis 1: Diagnosis and Management. The Journal for Nurse Practitioners. 2014;10(1):30-35.
  4. ↑ Genetics Home Reference. Neurofibromatosis type 1. Available at: http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1. Accessed March 4, 2014].
  5. ↑ Feldman DS, Jordan C, Fonseca L. Orthopaedic manifestations of neurofibromatosis type 1. J Am Acad Orthop Surg. 2010;18(6):346-57.
  6. ↑ Neurofibromatosis. Available at:http://www.youtube.com/watch?v=BQBKQB3zq9s
  7. ↑ Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81-8.
  8. ↑ Cancer net NF1 Available: https://www.cancer.net/cancer-types/neurofibromatosis-type-1 (accessed 6.3.2022)
  9. ↑ Johnson BA, Salzberg CL, Stevenson DA. Effects of a plyometric training program for 3 children with neurofibromatosis type 1. Pediatr Phys Ther. 2012;24(2):199-208.
  10. ↑ Helmers KM, Irwin KE. Physical therapy as conservative management for cervical pain and headaches in an adolescent with neurofibromatosis type 1: a case study. J Neurol Phys Ther. 2009;33(4):212-23.

 

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