- Email: [email protected]
Neurofibromatosis 1: Diagnosis and Management
Neurofibromatosis 1: Diagnosis and Management Nanette Julian, MS, AGNP, Nancy E. Edwards, PhD, ANP, Susan DeCrane, PhD, and Cynthia M. Hingtgen, MD, PhD ABSTRACT
Von Recklinghausen or neurofibromatosis type 1 is an autosomal dominant condition that results in skin changes and noncancerous tumors along the nerves in the body. It is blind in regards to ethnicity, race, or sex. With a prevalence rate of 1 in 3,000 to 1 in 3,500 individuals, it is likely that the nurse practitioner will encounter an individual with neurofibromatosis sometime in his/her career. The aim of this article is to give a brief synopsis of the etiology, clinical manifestations, and symptomatic treatment as well as guidance on monitoring, when to refer, health promotion, and teaching of the neurofibromatosis type 1 patient. Keywords: assessment, complications, neurofibromatosis, treatment Ó 2014 Elsevier, Inc. All rights reserved.
T
here are 2 main types of neurofibromatosis (NF), with NF type 1 (NF1) being the most common and accounting for about 90% of all cases.1 NF1, also known as Von Recklinghausen disease, is a condition that results in skin changes and noncancerous tumors along the nerves in the body.2 NF1 is blind in regards to ethnicity, race, or sex.3 It is an autosomal dominant disorder caused by a singlegene mutation or deletion.3 One half of all NF1 cases are spontaneous mutations, with the other half occurring as a result of inheritance.4 More than 100,000 individuals or about 1 in 3,000 to 3,500 in the United States are affected.5 NF2 occurs less frequently and is usually diagnosed in early adulthood. It affects approximately 1 in 50,000 individuals.6 Although the occurrence is less than NF1, because of the complications of NF2, individuals with this type have a shortened life expectancy and often experience blindness and deafness.6 This article focuses on NF1. ETIOLOGY
The NF1 gene is located within the long arm of chromosome 17. The exact role of the NF1 protein product neurofibromin is not fully understood. It is known that neurofibromin plays an important role in the regulation of the activity of Ras proteins. One 30
The Journal for Nurse Practitioners - JNP
role of these proteins is to relay instructions to the cells to promote cell division and growth.7 In normal individuals, neurofibromin helps inactivate Ras proteins. In individuals with NF1, neurofibromin is not present in sufficient quantities to inhibit cell growth properly. This results in the formation of neurofibromas along the nerves. These growths are generally benign but have the ability to become malignant.8 DIAGNOSIS
Early diagnosis is challenging because of its extremely variable characteristics. Some individuals may be mildly affected showing minimal signs, whereas others are severely afflicted.3 Typically, NF1 is diagnosed through clinical assessment including a thorough history and physical examination. These assessment findings are compared with standardized diagnostic criteria outlined by The National Institutes of Health (NIH). The NIH developed diagnostic criteria for NF1 based on clinical features that occur commonly.9 The diagnosis is made if an individual presents with 2 or more of the following features: 1. Six or more café au lait macules > 5 mm in prepubertal individuals and > 15 mm in diameter in adults (Figures 1 and 2)3 Volume 10, Issue 1, January 2014
Figure 1. Dark cafe au lait spots.
2. Two or more neurofibromas of any type; there are 4 types: cutaneous, subcutaneous, modular plexiform, and diffuse plexiform (Figure 3)3 3. Freckling in the axillary or inguinal regions (not generally apparent at birth but begin to appear around 4-5 years of age)3 4. Optic glioma visual pathway tumors most often presenting as grade I pilocytic astrocytomas a. Generally grow between the ages of 15 months to 7 years of age and then become dormant3 5. Two or more Lisch nodules: hyperpigmented spots on the iris (present in 90% of all individuals with NF1) (Figure 4)3 6. Abnormal development of the spine (scoliosis), the temple (sphenoid) bone, or the tibia6 7. A first-degree relative (parent, sibling, or offspring) with NF16
Figure 3. Neurofibromas.
Reprinted with permission from the University of California, San Diego, Catalog of Clinical Images. Available at: http://meded .ucsd.edu/clinicalimg/skin_cafe_aulait.htm.
Genetic testing is available; however, it is not indicated in most cases. Because of the cost of the test and the accuracy of diagnosis through clinical assessment, it is not a necessary component of diagnosis. Genetic testing may be useful in cases in Figure 4. Lisch nodules.
Figure 2. Light cafe au lait spots.
Reprinted with permission from Medscape Reference, 2013. Available at: http://emedicine.medscape.com/article/ 1219222-overview. www.npjournal.org
The Journal for Nurse Practitioners - JNP
31
which an individual has café au lait spots with no familial history or in the case of diagnosis during prenatal care.5 If a person with no family history of NF is diagnosed, an assessment of the family and/ or offspring for clinical manifestations should be pursued.
Table 2. Common manifestations of NF Cutaneous
Multiple café au lait spots (95% or less) Intertriginous freckling (65%-85%) Dermal neurofibromatosis (65%-85%) Xanthogranulomas (2%-5%) Hemangiomas (5%-10%)
Ophthalmologic
Optic nerve pathway tumor (15%) Lisch nodules (65%-85%) Glaucoma (rare)
Musculoskeletal
Cardiovascular
Hypertension (2%-5%) Congenital heart defect (2%)
Neurological
Tumors
Plexiform neurofibromas (50%) Malignant peripheral nerve sheath tumors (5%-10%) Central nervous system gliomas (2%) Pheochromocytoma, rhabdomyoma, neuroblastoma (1%) Mylogenous leukemia (rare, more common in children)
CLINICAL MANIFESTATIONS
Each person with NF1 presents uniquely as described in Table 1.3,5 It is rare for 1 person to experience all of the listed symptoms, but because it is difficult to predict the course the disease will take, close monitoring is essential to pick up potential complications. The most frequent features of NF1 include neurofibromas and café au lait spots. Other clinical manifestations commonly associated with NF1 are outlined in Table 2.10 Because of the frequent presentation of tumors, research needs to be done on the possible correlation of cancer and NF1. It is estimated that 3%-5% of Table 1. Definitions of Common Manifestations Café au lait spots: light brown flat spots with smooth borders located anywhere on the body, the most common feature of NF1.3,5 Cutaneous neurofibromas: the most common type of tumor in NF1 individuals. They are generally dome shaped and are soft and fleshy; they start to become apparent in puberty.5 Subcutaneous neurofibromas: similar to cutaneous tumors but are firm and nodular.3,5 Plexiform neurofibromas: tumors that arise from nerves in the skin or more internal nerve bundles; can be very large. Internal plexiforms can damage healthy tissue and organs. Generally lie under large café au lait spots.5 Optic gliomas: tumors that arise from glial cells, which are supportive brain cells; can affect 1 or both eyes. Generally slow growing but can cause visual loss.3,5 Lisch nodules: hyperpigmented spots on the iris. Harmless but are a good diagnostic tool; 99% of affected individuals over the age of 20 will present with 1 or more Lisch nodules.3,5 Scoliosis: curvature of the spine in a sideways or lateral orientation; common in early adolescence. Treatment: self-limiting or bracing.3,5 Tibial dysplasia: inappropriate development of tibia, which may contribute to fractures and pseudarthrosis or failure of fractures to heal properly.3,5
32
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Sphenoid wing dysplasia (1%) Long-bone bowing (2%-5%) Scoliosis (20%) Short stature (25%-35%) Relative macrocephaly (45%)
Hydrocephalus (5%) Enlarged head circumference Seizures (11%) Educational/learning difficulties (40%-60%) Sensorineural hearing loss (5%) Precocious puberty (2%-5%)
Data from Neurofibromatosis Midwest.10
tumors associated with NF1 will become malignant; therefore, vigilance is required.6 TREATMENT
A major role of the health care provider is to explore avenues for symptomatic treatment. It is imperative that the patient and health care provider maintain open communication. As long as an individual does not exhibit serious manifestations of NF such as debilitating tumors or a malignancy, the health promotion needs are similar to that of any healthy individual. The following are recommendations for implementing a plan of care in the NF patient: Volume 10, Issue 1, January 2014
1. Referral to a physician with experience treating NF: most major cities have NF clinics staffed by physicians who specialize in the diagnosis and treatment of NF. Patients not exhibiting serious problems are encouraged to see their NF specialist yearly. 2. Neurofibromas can cause pain, tenderness, and itching; there is currently no treatment for them. Diphenhydramine has been shown to give comfort and relief for itching.11 Routinely removing neurofibromas is futile because they most likely will recur.12 Removal may be indicated when the neurofibromas affect quality of life such as discomfort in wearing a bra or impair the ability to shave. In these cases, referral to a dermatologist or surgeon may be advised. 3. Yearly eye examinations by an ophthalmologist are essential in children under the age of 10 and may be necessary in older children. It is important for the health care provider to detect any visual changes through a review of systems interview and physical examination. Referral as indicated. 4. Annual monitoring of blood pressure should be conducted.13 Vascular disease has received little recognition in relation to NF.13 In some cases, the widespread changes in the vascular system may lead to organ damage. 13 5. Because of the unpredictability of the disease process combined with the possible erratic growth of deforming cutaneous neurofibromas, depression and/or anxiety are common manifestations. Depression and anxiety screening should be conducted at every visit with possible referral for counseling and or medications if indicated. Support groups, face-to-face or online, often provide invaluable social and emotional support and should be recommended.3 6. Roughly 40% of children with NF1 have learning disabilities.14 Problems with spatial memory and learning, social and/or behavioral problems, and attention-deficit/hyperactivity disorders are common features. The etiology of these problems is unknown, but enhanced concentration and improved test scores have www.npjournal.org
been noted in patients receiving methylphenidate.15 The health care provider needs to assess school performance and socialization. 7. Genetic counseling is imperative in this population. Patients and families must be aware that NF1 is an autosomal dominate disorder.3,5 An affected individual has a 50% chance of passing the disorder to their offspring. Clinicians should be aware that half of NF1 cases are inherited, whereas the other half occur as a result of a spontaneous gene mutation at conception.3,5 The patients and their family should be counseled on family planning.3 Although 75% of neurofibromas carry progesterone receptors, there is little to no correlation between combined estrogen/ progesterone oral contraceptive use and neurofibroma growth in women taking this medication. However, significant neurofibroma growth was noted in 2 women who used depot medroxyprogesterone acetate; therefore, women with NF may need to avoid high-dose progesterone.16 Because NF1 is a progressive disorder with no known cure, research trials are continually initiated to devise better methods to care for individuals with NF. Individuals can be referred to research trial websites that outline the purpose and inclusion criteria for current studies (Table 3). RESOURCES/EDUCATION
As long as a patient is not experiencing serious manifestations of NF, such as debilitating tumors and or malignancies, the health promotion needs are similar to that of any healthy individual. The primary care provider should work with his/her patient to educate and encourage a healthy lifestyle including diet, exercise, and the avoidance of recreational drugs, tobacco abuse, and excessive alcohol. The importance of yearly physical examinations must be reinforced to pick up on potential complications early. Recommended assessments needed at specific ages for patients with NF1 are outlined in Table 4. This chart applies to all races, ethnicities, and sexes. Web resources are available for additional education for both patients/families and health professionals (Table 3). The Journal for Nurse Practitioners - JNP
33
Table 3. Resources: Educational and Research/Clinical Trials
Table 4. Recommended Assessments by Age
Education
Research/Clinical Trials
Children’s Tumor Foundation 95 Pine Street 16th Floor New York, New York 10005 Telephone: 1-800-323-7938 or 212-344-6633; Fax: 212-747-0004 E-mail: [email protected] Website: http://www.ctf.org
NF Registry www.nfregistry.org
0-8
Complete physical (yearly) Skin assessments Bone asymmetry Eye examination Language and development
Optic gliomas Scoliosis Tibia dysplasia Learning disabilities Hypertension
8-15
Learning disabilities Neurofibromas Hypertension Anxiety/depression
NF Network http://www.nfnetwork.org/
Clinical Trials.gov Clinicaltrials.gov/show/ NCT00924196
Complete physical (yearly) School performance Knowledge of NF Skin assessment Depression scale Sexual activity
16-21
Complete physical (yearly) Skin assessment Possible imaging studies Sexual activity
Neurofibromas Appearance issues Complaints of pain Malignancies Hypertension Anxiety/depression
> 21
Complete physical (yearly) Pain Neurofibromas Depression scale Psychosocial Job/careers Family
Hypertension Risk of cancer Depression Anxiety/depression
Genetics Home Reference US National Library of Medicine ghr.nlm.nih.gov/condition/ neurofibromatosis-type-1
IMPLICATIONS FOR NPs
NF1 is an extremely variable disorder.3 Many individuals are unaware that they have the disease. The diagnosis often catches the patient off guard because they are diagnosed when they see their health care provider for a routine physical examination. However, the diagnosis is missed on many individuals. The majority of individuals are diagnosed in the primary care setting; therefore, NPs must be aware of the diagnostic criteria. The role of the primary care provider is to diagnose the individuals and to refer the NF patient appropriately. The NP advocates for the NF patient who generally requires a health care team of specialists such as dermatologists, neurologists, psychologists, ophthalmologists, and orthopedists in order to provide comprehensive care. In addition, their primary care NP along with the NF specialist is vital in assessing and monitoring for potential complications and ensuring that referrals are made as indicated. The role of the NP as a health coach is to facilitate healthy behaviors, help the patient to identify and achieve health-related goals, and to help promote quality of life.17 Assisting the patient to explore 34
Potential Health Findings Related to NF1
Age
The Journal for Nurse Practitioners - JNP
Assessment
Data from Tonsgard.3
the impact of NF on their life and being sensitive to how the patient is adapting to the diagnosis is a vital function of the NP. They can assist the patient as they learn to live with the uncertainty of their disease and encourage participation in support groups. The NF patient must be educated about the disease and its progression, available resources and tips to help ease the discomfort, and current research trials that may be associated with NF1. The primary health provider will work 1 on 1 with the NF patient in a nonprejudicial, nonjudgmental way to help unlock the patients’ potential and maximize their performance. NF can be a devastating disorder, but with the right medical team, proper teaching, and effective wellness coaching, individuals can lead healthy and productive lives. Volume 10, Issue 1, January 2014
References 1. Ilyayev R, Patel B. Middle aged woman with myriad growths. Consultant. 2013;53(1):32-33. 2. Children’s Hospitals and Clinics of Minnesota: Patient and family education. Neurofibromatosis type 1. Children’s Hospitals and Clinics of Minnesota: Patient and family education. http://www.childrensmn.org/manuals/pfs/ condill/106842.pdf. 2007. Accessed January 24, 2013. 3. Tonsgard JH. Clinical manifestations and management of neurofibromatosis type 1. Sem Pediatr Neurol. 2006;13:2-7. 4. Pletcher BA, Buehler B. Genetics of neurofibromatosis. Medscape Reference: Drugs, Diseases, & Procedures. Updated July 8, 2011. http://emedicine.medscape .com/article/950151-overview#showall. Accessed November 6, 2012. 5. Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61(1):1-14. 6. National Institute of Neurological Disorders and Stroke. Neurofibromatosis fact sheet. http://www.ninds.nih.gov/disorders/neurofibromatosis/detail_ neurofibromatosis.htm#192783162. Updated January 13, 2012. Accessed June 2, 2012. 7. Han D, Spengler B, Ross R. Increased wild-Type N-Ras activation by neurofibromin down regulation increases human neuroblastoma stem cell malignancy. Genes Cancer. 2012;2(11):1034-1043. 8. Weiss B, Bollag G, Shannon K. Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet. 1999;89(1):14-22. 9. Plon SE, Blazo M. Neurofibromatosis type 1 (von Recklinghausen’s disease). Up to Date. Updated April 29, 2011. http://www.uptodate.com/contents/ neurofibromatosis-type-1-von-recklinghausens-disease. Accessed July 15, 2012. 10. A publication by NF Midwest for Neurofibromatosis Families. http://www .nfmidwest.org. Accessed January 2, 2013. 11. Ogbru O, Marks J. Diphenhydramine, Benadryl. Medicine Net.com. http:// www.medicinenet.com/diphenhydramine/article.htm. Updated November 2, 2008. Accessed October 16, 2012. 12. Riccardi V. The genetic predisposition to and histogenesis of neurofibromas and neurofibrosarcoma in neurofibromatosis type 1. Neurosurg Focus. 2007;22(6):E3. 13. Tedesco MA, Di Salvo G, Ratti G, et al. Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1. Am J Hypertens. 2001;14:559-566.
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14. Gutmann D. Learning disabilities in neurofibromatosis 1: sizing up the brain. JAMA Neurol. 1999;56(11):1322-1323. 15. Mautner V, Kluwe L, Thakker S, et al. Treatment of ADHD in neurofibromatosis type 1. Dev Med Child Neurol. 2002;44:164-170. 16. Member’s enquiry response. Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit. http://www.fsrh.org/pdfs/Enquiry_Response_3399 .pdf. Published January 24, 2011. Accessed January 24, 2013. 17. Heady SA. Health Education. In: Edelman CL, Mandle CL, eds. Health Promotion Throughout the Lifespan. St. Louis, MO: Mosby Elsevier; 2010:243-257.
Nanette Julian, MS, AGNP, is a nurse practitioner at Indiana University Health in Lafayette, IN; she can be reached at [email protected]. Nancy E. Edwards, PhD, MS, ANP, is an associate professor and Susan DeCrane, PhD, is an assistant professor at the Purdue University School of Nursing in West Lafayette, IN. Cynthia M. Hingtgen, MD, PhD, is a physician and clinical professor with Spectrum Health Medical Group, Michigan State University College of Human Medicine in East Lansing, MI. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest. 1555-4155/13/$ see front matter © 2014 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2013.07.001
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Von Recklinghausen or neurofibromatosis type 1 is an autosomal dominant condition that results in skin changes and noncancerous tumors along the nerves in the body. It is blind in regards to ethnicity, race, or sex. With a prevalence rate of 1 in 3,000 to 1 in 3,500 individuals, it is likely that the nurse practitioner will encounter an individual with neurofibromatosis sometime in his/her career. The aim of this article is to give a brief synopsis of the etiology, clinical manifestations, and symptomatic treatment as well as guidance on monitoring, when to refer, health promotion, and teaching of the neurofibromatosis type 1 patient. Keywords: assessment, complications, neurofibromatosis, treatment Ó 2014 Elsevier, Inc. All rights reserved.
T
here are 2 main types of neurofibromatosis (NF), with NF type 1 (NF1) being the most common and accounting for about 90% of all cases.1 NF1, also known as Von Recklinghausen disease, is a condition that results in skin changes and noncancerous tumors along the nerves in the body.2 NF1 is blind in regards to ethnicity, race, or sex.3 It is an autosomal dominant disorder caused by a singlegene mutation or deletion.3 One half of all NF1 cases are spontaneous mutations, with the other half occurring as a result of inheritance.4 More than 100,000 individuals or about 1 in 3,000 to 3,500 in the United States are affected.5 NF2 occurs less frequently and is usually diagnosed in early adulthood. It affects approximately 1 in 50,000 individuals.6 Although the occurrence is less than NF1, because of the complications of NF2, individuals with this type have a shortened life expectancy and often experience blindness and deafness.6 This article focuses on NF1. ETIOLOGY
The NF1 gene is located within the long arm of chromosome 17. The exact role of the NF1 protein product neurofibromin is not fully understood. It is known that neurofibromin plays an important role in the regulation of the activity of Ras proteins. One 30
The Journal for Nurse Practitioners - JNP
role of these proteins is to relay instructions to the cells to promote cell division and growth.7 In normal individuals, neurofibromin helps inactivate Ras proteins. In individuals with NF1, neurofibromin is not present in sufficient quantities to inhibit cell growth properly. This results in the formation of neurofibromas along the nerves. These growths are generally benign but have the ability to become malignant.8 DIAGNOSIS
Early diagnosis is challenging because of its extremely variable characteristics. Some individuals may be mildly affected showing minimal signs, whereas others are severely afflicted.3 Typically, NF1 is diagnosed through clinical assessment including a thorough history and physical examination. These assessment findings are compared with standardized diagnostic criteria outlined by The National Institutes of Health (NIH). The NIH developed diagnostic criteria for NF1 based on clinical features that occur commonly.9 The diagnosis is made if an individual presents with 2 or more of the following features: 1. Six or more café au lait macules > 5 mm in prepubertal individuals and > 15 mm in diameter in adults (Figures 1 and 2)3 Volume 10, Issue 1, January 2014
Figure 1. Dark cafe au lait spots.
2. Two or more neurofibromas of any type; there are 4 types: cutaneous, subcutaneous, modular plexiform, and diffuse plexiform (Figure 3)3 3. Freckling in the axillary or inguinal regions (not generally apparent at birth but begin to appear around 4-5 years of age)3 4. Optic glioma visual pathway tumors most often presenting as grade I pilocytic astrocytomas a. Generally grow between the ages of 15 months to 7 years of age and then become dormant3 5. Two or more Lisch nodules: hyperpigmented spots on the iris (present in 90% of all individuals with NF1) (Figure 4)3 6. Abnormal development of the spine (scoliosis), the temple (sphenoid) bone, or the tibia6 7. A first-degree relative (parent, sibling, or offspring) with NF16
Figure 3. Neurofibromas.
Reprinted with permission from the University of California, San Diego, Catalog of Clinical Images. Available at: http://meded .ucsd.edu/clinicalimg/skin_cafe_aulait.htm.
Genetic testing is available; however, it is not indicated in most cases. Because of the cost of the test and the accuracy of diagnosis through clinical assessment, it is not a necessary component of diagnosis. Genetic testing may be useful in cases in Figure 4. Lisch nodules.
Figure 2. Light cafe au lait spots.
Reprinted with permission from Medscape Reference, 2013. Available at: http://emedicine.medscape.com/article/ 1219222-overview. www.npjournal.org
The Journal for Nurse Practitioners - JNP
31
which an individual has café au lait spots with no familial history or in the case of diagnosis during prenatal care.5 If a person with no family history of NF is diagnosed, an assessment of the family and/ or offspring for clinical manifestations should be pursued.
Table 2. Common manifestations of NF Cutaneous
Multiple café au lait spots (95% or less) Intertriginous freckling (65%-85%) Dermal neurofibromatosis (65%-85%) Xanthogranulomas (2%-5%) Hemangiomas (5%-10%)
Ophthalmologic
Optic nerve pathway tumor (15%) Lisch nodules (65%-85%) Glaucoma (rare)
Musculoskeletal
Cardiovascular
Hypertension (2%-5%) Congenital heart defect (2%)
Neurological
Tumors
Plexiform neurofibromas (50%) Malignant peripheral nerve sheath tumors (5%-10%) Central nervous system gliomas (2%) Pheochromocytoma, rhabdomyoma, neuroblastoma (1%) Mylogenous leukemia (rare, more common in children)
CLINICAL MANIFESTATIONS
Each person with NF1 presents uniquely as described in Table 1.3,5 It is rare for 1 person to experience all of the listed symptoms, but because it is difficult to predict the course the disease will take, close monitoring is essential to pick up potential complications. The most frequent features of NF1 include neurofibromas and café au lait spots. Other clinical manifestations commonly associated with NF1 are outlined in Table 2.10 Because of the frequent presentation of tumors, research needs to be done on the possible correlation of cancer and NF1. It is estimated that 3%-5% of Table 1. Definitions of Common Manifestations Café au lait spots: light brown flat spots with smooth borders located anywhere on the body, the most common feature of NF1.3,5 Cutaneous neurofibromas: the most common type of tumor in NF1 individuals. They are generally dome shaped and are soft and fleshy; they start to become apparent in puberty.5 Subcutaneous neurofibromas: similar to cutaneous tumors but are firm and nodular.3,5 Plexiform neurofibromas: tumors that arise from nerves in the skin or more internal nerve bundles; can be very large. Internal plexiforms can damage healthy tissue and organs. Generally lie under large café au lait spots.5 Optic gliomas: tumors that arise from glial cells, which are supportive brain cells; can affect 1 or both eyes. Generally slow growing but can cause visual loss.3,5 Lisch nodules: hyperpigmented spots on the iris. Harmless but are a good diagnostic tool; 99% of affected individuals over the age of 20 will present with 1 or more Lisch nodules.3,5 Scoliosis: curvature of the spine in a sideways or lateral orientation; common in early adolescence. Treatment: self-limiting or bracing.3,5 Tibial dysplasia: inappropriate development of tibia, which may contribute to fractures and pseudarthrosis or failure of fractures to heal properly.3,5
32
The Journal for Nurse Practitioners - JNP
Sphenoid wing dysplasia (1%) Long-bone bowing (2%-5%) Scoliosis (20%) Short stature (25%-35%) Relative macrocephaly (45%)
Hydrocephalus (5%) Enlarged head circumference Seizures (11%) Educational/learning difficulties (40%-60%) Sensorineural hearing loss (5%) Precocious puberty (2%-5%)
Data from Neurofibromatosis Midwest.10
tumors associated with NF1 will become malignant; therefore, vigilance is required.6 TREATMENT
A major role of the health care provider is to explore avenues for symptomatic treatment. It is imperative that the patient and health care provider maintain open communication. As long as an individual does not exhibit serious manifestations of NF such as debilitating tumors or a malignancy, the health promotion needs are similar to that of any healthy individual. The following are recommendations for implementing a plan of care in the NF patient: Volume 10, Issue 1, January 2014
1. Referral to a physician with experience treating NF: most major cities have NF clinics staffed by physicians who specialize in the diagnosis and treatment of NF. Patients not exhibiting serious problems are encouraged to see their NF specialist yearly. 2. Neurofibromas can cause pain, tenderness, and itching; there is currently no treatment for them. Diphenhydramine has been shown to give comfort and relief for itching.11 Routinely removing neurofibromas is futile because they most likely will recur.12 Removal may be indicated when the neurofibromas affect quality of life such as discomfort in wearing a bra or impair the ability to shave. In these cases, referral to a dermatologist or surgeon may be advised. 3. Yearly eye examinations by an ophthalmologist are essential in children under the age of 10 and may be necessary in older children. It is important for the health care provider to detect any visual changes through a review of systems interview and physical examination. Referral as indicated. 4. Annual monitoring of blood pressure should be conducted.13 Vascular disease has received little recognition in relation to NF.13 In some cases, the widespread changes in the vascular system may lead to organ damage. 13 5. Because of the unpredictability of the disease process combined with the possible erratic growth of deforming cutaneous neurofibromas, depression and/or anxiety are common manifestations. Depression and anxiety screening should be conducted at every visit with possible referral for counseling and or medications if indicated. Support groups, face-to-face or online, often provide invaluable social and emotional support and should be recommended.3 6. Roughly 40% of children with NF1 have learning disabilities.14 Problems with spatial memory and learning, social and/or behavioral problems, and attention-deficit/hyperactivity disorders are common features. The etiology of these problems is unknown, but enhanced concentration and improved test scores have www.npjournal.org
been noted in patients receiving methylphenidate.15 The health care provider needs to assess school performance and socialization. 7. Genetic counseling is imperative in this population. Patients and families must be aware that NF1 is an autosomal dominate disorder.3,5 An affected individual has a 50% chance of passing the disorder to their offspring. Clinicians should be aware that half of NF1 cases are inherited, whereas the other half occur as a result of a spontaneous gene mutation at conception.3,5 The patients and their family should be counseled on family planning.3 Although 75% of neurofibromas carry progesterone receptors, there is little to no correlation between combined estrogen/ progesterone oral contraceptive use and neurofibroma growth in women taking this medication. However, significant neurofibroma growth was noted in 2 women who used depot medroxyprogesterone acetate; therefore, women with NF may need to avoid high-dose progesterone.16 Because NF1 is a progressive disorder with no known cure, research trials are continually initiated to devise better methods to care for individuals with NF. Individuals can be referred to research trial websites that outline the purpose and inclusion criteria for current studies (Table 3). RESOURCES/EDUCATION
As long as a patient is not experiencing serious manifestations of NF, such as debilitating tumors and or malignancies, the health promotion needs are similar to that of any healthy individual. The primary care provider should work with his/her patient to educate and encourage a healthy lifestyle including diet, exercise, and the avoidance of recreational drugs, tobacco abuse, and excessive alcohol. The importance of yearly physical examinations must be reinforced to pick up on potential complications early. Recommended assessments needed at specific ages for patients with NF1 are outlined in Table 4. This chart applies to all races, ethnicities, and sexes. Web resources are available for additional education for both patients/families and health professionals (Table 3). The Journal for Nurse Practitioners - JNP
33
Table 3. Resources: Educational and Research/Clinical Trials
Table 4. Recommended Assessments by Age
Education
Research/Clinical Trials
Children’s Tumor Foundation 95 Pine Street 16th Floor New York, New York 10005 Telephone: 1-800-323-7938 or 212-344-6633; Fax: 212-747-0004 E-mail: [email protected] Website: http://www.ctf.org
NF Registry www.nfregistry.org
0-8
Complete physical (yearly) Skin assessments Bone asymmetry Eye examination Language and development
Optic gliomas Scoliosis Tibia dysplasia Learning disabilities Hypertension
8-15
Learning disabilities Neurofibromas Hypertension Anxiety/depression
NF Network http://www.nfnetwork.org/
Clinical Trials.gov Clinicaltrials.gov/show/ NCT00924196
Complete physical (yearly) School performance Knowledge of NF Skin assessment Depression scale Sexual activity
16-21
Complete physical (yearly) Skin assessment Possible imaging studies Sexual activity
Neurofibromas Appearance issues Complaints of pain Malignancies Hypertension Anxiety/depression
> 21
Complete physical (yearly) Pain Neurofibromas Depression scale Psychosocial Job/careers Family
Hypertension Risk of cancer Depression Anxiety/depression
Genetics Home Reference US National Library of Medicine ghr.nlm.nih.gov/condition/ neurofibromatosis-type-1
IMPLICATIONS FOR NPs
NF1 is an extremely variable disorder.3 Many individuals are unaware that they have the disease. The diagnosis often catches the patient off guard because they are diagnosed when they see their health care provider for a routine physical examination. However, the diagnosis is missed on many individuals. The majority of individuals are diagnosed in the primary care setting; therefore, NPs must be aware of the diagnostic criteria. The role of the primary care provider is to diagnose the individuals and to refer the NF patient appropriately. The NP advocates for the NF patient who generally requires a health care team of specialists such as dermatologists, neurologists, psychologists, ophthalmologists, and orthopedists in order to provide comprehensive care. In addition, their primary care NP along with the NF specialist is vital in assessing and monitoring for potential complications and ensuring that referrals are made as indicated. The role of the NP as a health coach is to facilitate healthy behaviors, help the patient to identify and achieve health-related goals, and to help promote quality of life.17 Assisting the patient to explore 34
Potential Health Findings Related to NF1
Age
The Journal for Nurse Practitioners - JNP
Assessment
Data from Tonsgard.3
the impact of NF on their life and being sensitive to how the patient is adapting to the diagnosis is a vital function of the NP. They can assist the patient as they learn to live with the uncertainty of their disease and encourage participation in support groups. The NF patient must be educated about the disease and its progression, available resources and tips to help ease the discomfort, and current research trials that may be associated with NF1. The primary health provider will work 1 on 1 with the NF patient in a nonprejudicial, nonjudgmental way to help unlock the patients’ potential and maximize their performance. NF can be a devastating disorder, but with the right medical team, proper teaching, and effective wellness coaching, individuals can lead healthy and productive lives. Volume 10, Issue 1, January 2014
References 1. Ilyayev R, Patel B. Middle aged woman with myriad growths. Consultant. 2013;53(1):32-33. 2. Children’s Hospitals and Clinics of Minnesota: Patient and family education. Neurofibromatosis type 1. Children’s Hospitals and Clinics of Minnesota: Patient and family education. http://www.childrensmn.org/manuals/pfs/ condill/106842.pdf. 2007. Accessed January 24, 2013. 3. Tonsgard JH. Clinical manifestations and management of neurofibromatosis type 1. Sem Pediatr Neurol. 2006;13:2-7. 4. Pletcher BA, Buehler B. Genetics of neurofibromatosis. Medscape Reference: Drugs, Diseases, & Procedures. Updated July 8, 2011. http://emedicine.medscape .com/article/950151-overview#showall. Accessed November 6, 2012. 5. Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61(1):1-14. 6. National Institute of Neurological Disorders and Stroke. Neurofibromatosis fact sheet. http://www.ninds.nih.gov/disorders/neurofibromatosis/detail_ neurofibromatosis.htm#192783162. Updated January 13, 2012. Accessed June 2, 2012. 7. Han D, Spengler B, Ross R. Increased wild-Type N-Ras activation by neurofibromin down regulation increases human neuroblastoma stem cell malignancy. Genes Cancer. 2012;2(11):1034-1043. 8. Weiss B, Bollag G, Shannon K. Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet. 1999;89(1):14-22. 9. Plon SE, Blazo M. Neurofibromatosis type 1 (von Recklinghausen’s disease). Up to Date. Updated April 29, 2011. http://www.uptodate.com/contents/ neurofibromatosis-type-1-von-recklinghausens-disease. Accessed July 15, 2012. 10. A publication by NF Midwest for Neurofibromatosis Families. http://www .nfmidwest.org. Accessed January 2, 2013. 11. Ogbru O, Marks J. Diphenhydramine, Benadryl. Medicine Net.com. http:// www.medicinenet.com/diphenhydramine/article.htm. Updated November 2, 2008. Accessed October 16, 2012. 12. Riccardi V. The genetic predisposition to and histogenesis of neurofibromas and neurofibrosarcoma in neurofibromatosis type 1. Neurosurg Focus. 2007;22(6):E3. 13. Tedesco MA, Di Salvo G, Ratti G, et al. Arterial distensibility and ambulatory blood pressure monitoring in young patients with neurofibromatosis type 1. Am J Hypertens. 2001;14:559-566.
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14. Gutmann D. Learning disabilities in neurofibromatosis 1: sizing up the brain. JAMA Neurol. 1999;56(11):1322-1323. 15. Mautner V, Kluwe L, Thakker S, et al. Treatment of ADHD in neurofibromatosis type 1. Dev Med Child Neurol. 2002;44:164-170. 16. Member’s enquiry response. Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit. http://www.fsrh.org/pdfs/Enquiry_Response_3399 .pdf. Published January 24, 2011. Accessed January 24, 2013. 17. Heady SA. Health Education. In: Edelman CL, Mandle CL, eds. Health Promotion Throughout the Lifespan. St. Louis, MO: Mosby Elsevier; 2010:243-257.
Nanette Julian, MS, AGNP, is a nurse practitioner at Indiana University Health in Lafayette, IN; she can be reached at [email protected]. Nancy E. Edwards, PhD, MS, ANP, is an associate professor and Susan DeCrane, PhD, is an assistant professor at the Purdue University School of Nursing in West Lafayette, IN. Cynthia M. Hingtgen, MD, PhD, is a physician and clinical professor with Spectrum Health Medical Group, Michigan State University College of Human Medicine in East Lansing, MI. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest. 1555-4155/13/$ see front matter © 2014 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2013.07.001
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