Neurofibromatosis
Neurofibromatosis: Excerpt from The 5-Minute Pediatric Consult
Leah Burke, MD
Neurofibromatosis - BASICS
Neurofibromatosis - description
Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome in which tumors grow along peripheral nerves or nerve roots within the spinal canal. Neurologic features include cognitive disability, intracranial and extracranial tumors of the nervous system; less common are epilepsy, autism, and stroke.
- Diagnosis is based on the presence of any 2 of the following physical/familial criteria:
- 2 or more cutaneous neurofibromas or 1 plexiform neurofibroma
- 2 or more Lisch nodules
- Inguinal or axillary freckling
- 6 or more (smooth-edged) café au lait spots, at least 1.5 cm in diameter in postpubertal individuals or 0.5 cm in diameter in prepubertal individuals
- Optic nerve glioma
- Osseous lesions, including sphenoid wing dysplasia, pseudoarthrosis
- A 1st-degree relative (parent, sibling, or offspring) with NF
- Tumors may be cosmetically disfiguring and physically limiting; they rarely undergo sarcomatous transformation.
Neurofibromatosis - epidemiology
Independent of sex, race, or environmental factors
Neurofibromatosis - incidence
1 in every 3,000–4,000 live births
Neurofibromatosis - prevalence
NF1 affects 100,000 Americans.
Neurofibromatosis - risk factors
Neurofibromatosis - genetics
- 50% of the cases are inherited; others occur as a sporadic (new) mutation.
- One of the most commonly inherited autosomal dominant disorders (~1 in 4,000), with no known gender or ethnic predisposition
- NF1 gene is located on chromosome 17.
- Expression varies widely within and among families, from mildly affected to severely impaired.
- Course impossible to predict; relative’s disease will not be an indication of progression
Neurofibromatosis - etiology
Genetic predisposition
Neurofibromatosis - associated conditions
- Head circumference >98% percentile
- Developmental speech delay, motor incoordination, learning disorders, attention deficit disorder
- Hypertension
- Brain tumor, Moyamoya disease
- Sarcoma, leukemia, Wilms tumor, pheochromocytoma
- Headaches, scoliosis
- Abnormalities in growth, hemihypertrophy
Neurofibromatosis - DIAGNOSIS
Neurofibromatosis - signs & symptoms
Neurofibromatosis - history
- “Positive family history”: Affecting a 1st-degree relative, mother, or father of the proband: The disorder shows 100% penetrance.
- Vision: Optic pathway tumors (OPTs) generally occur between the ages of 2 and 6 years.
- Development: Learning problems and attention deficit hyperactivity disorder (ADHD), >50%.
- Seizures: More common in NF
- Joint/Extremity pain: Neuropathic pain or abrasion owing to neurofibroma
- Back pain: Could signal potentially serious cord or root compression
- Headache: Hydrocephalus; migraine also common in NF
- Respiratory problems
- Neurofibromas may encroach on the airway; sexual development, abnormalities owing to hypothalamic disease, psychiatric/behavioral symptoms, and depression are common.
Neurofibromatosis - physical exam
- Café au lait spots are noted at birth or within the 1st year of life:
- Macules are generally flush and circular, although they may have jagged edges or areas of hypertrichosis.
- Café au lait spots result from a collection of heavily pigmented melanocytes of neural crest origin in the epidermis.
- The macules will appear for the 1st 5 years of life and then slow or stop, although they will grow with the child.
- Axillary and inguinal freckling is generally seen by puberty. The freckling is a cluster often seen in the skin folds.
- Lisch nodules are best assessed by slit-lamp examination:
- Small bumps on the iris that do not interfere with vision
- They are uncommon during infancy, but by age 20, 99% of patients with NF1 have Lisch nodules.
- OPTs are present in 20% of patients with NF1, although only ~20% of those will require intervention:
- Funduscopy and acuity check for evidence of OPT
- Treatment should be limited to those patients who have uncorrectable visual acuity, a change in visual fields, and/or endocrine abnormalities, or to those lesions that extend to the hypothalamus.
- Bony dysplasias occur in ~3% of patients with NF1:
- Dysplasias especially affecting the tibia or the sphenoid wing
- A pseudoarthrosis: Due to thinning of the long bone and its inability to heal after it breaks
- Hypertension
- Review of palpable tumors for extension or “stony” feel that could signal cancerous change
- Abdominal examination for masses
- Neck and spine palpation/mobility
- Reflexes for evidence of nerve root tumor
- Growth parameters (including head circumference) for evidence of hydrocephalus, hypothalamic disturbance
- Scoliosis
Neurofibromatosis - tests
In most cases, the diagnosis of NF1 remains a clinical diagnosis. Tests are necessary to find the complications of neurofibromas.
- DNA testing has become more available and therefore may be useful in atypical cases or in making reproductive choices:
- DNA-based testing of the NF1 gene is undertaken in a stepwise approach using a cascade of complementary tests that are able to detect a mutation in the NF1 gene in 95% of patients who meet the National Institutes of Health (NIH) diagnostic criteria.
Neurofibromatosis - lab
Renal studies may be indicated for persistent hypertension or difficulty with urine flow.
Neurofibromatosis - imaging
MRI:
- Bright areas in cerebral white matter on TIndications for neuroimaging depend on findings such as progressive macrocrania, sensory deficits (especially visual), new-onset seizure, and chronic headaches.
- In patients with hypertension, neurofibromas impinging on the renal artery causing renal ischemia may be seen.
- Some clinicians obtain a scan as a baseline on all new cases, but this is controversial.
Neurofibromatosis - pathological findings
Biopsy of tumors that are enlarging, as this may be evidence of sarcomatous change
Neurofibromatosis - differencial diagnosis
- Café au lait spots are most often benign findings unrelated to NF.
- NF2 may resemble NF1:
- NF1 versus NF2: NF2 is also known as central bilateral acoustic NF, a rare disorder characterized by multiple tumors on the cranial and spinal nerves and by other lesions of the brain and spinal cord.
- NF2 is genetically and clinically distinct from NF1. The NF2 gene is located on chromosome 22.
- The diagnosis of NF2 is made if the individual has the following: Bilateral acoustic neuromas or a 1st-degree relative with NF2 and either a unilateral acoustic neuroma or 2 of the following: Meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacity.
- Sotos syndrome features macrosomia, hypertelorism, ventriculomegaly, and cognitive difficulties.
- McCune-Albright syndrome has large café au lait spots with irregular margins and polyostotic fibrous dysplasia.
- Tuberous sclerosis (TS) may share autosomal dominant transmission and café au lait lesions in common with NF:
- Features distinctive for TS include adenomal sebaceum, cardiac and renal tumors, and prominent epilepsy.
- Genetic testing for TS may soon be available.
Neurofibromatosis - TREATMENT
Neurofibromatosis - general measures
- There is no treatment for tumor growth except surgical intervention.
- Interventions are palliative and supportive.
Neurofibromatosis - surgery
Surgical intervention is performed on those tumors that are medically compromising, painful, or cosmetically disfiguring:
- SC nodules are flesh-colored, raised, pealike nodules that may be present during childhood.
- These commonly appear and grow during puberty or pregnancy and do not grow into plexiform tumors.
Neurofibromatosis - FOLLOW UP
- Anticipatory care issues are pertinent to follow-up.
- Optimism: Natural history studies indicate that people with NF1 can live long, full lives.
- Pitfalls:
- Macrocrania is a common feature of NF, but growth curve for the head is necessary to determine whether it signifies a concern.
- Regrowth of plexiform neurofibromas: Even after apparent total resection, regrowth is common and should be discussed before surgery.
- The possibility of nerve injury after surgery on plexiform neurofibromas should also be discussed with the family/individual before surgery.
Neurofibromatosis - disposition
Neurofibromatosis - issues for referral
Orthopedic, oncologic, endocrine, surgery, and plastic surgery consultants may be helpful, depending on individual issues.
Neurofibromatosis - prognosis
- Deaths have been associated with cancer, heart disease, and strokes, similar to the general population.
- Tumors cannot be predicted on the basis of their occurrence in another member of the family with NF.
Neurofibromatosis - complications
- Oncologic:
- Neurofibromas are benign tumors of Schwann cells, nerve fibers, and fibroblasts that arise along the nerves.
- Plexiform neurofibromas occur in ~15% of patients with NF1; these are extensive tumors that grow along the nerve root and may invade adjacent structures, threatening vital structures (especially in the neck and throat), or cause gross disfigurement. ~10% of these tumors undergo sarcomatous degeneration.
- CNS tumors include optic nerve/pathway gliomas or gliomas elsewhere in the brain.
- Neurologic: Learning disability, language disorders, incoordination, autism, seizures, retardation, and attention deficit occur with higher-than-background frequency in NF.
- Renal: Hypertension
- Circulatory:
- Endocrine: Pheochromocytoma
- Hematologic: Leukemia
Neurofibromatosis - patient monitoring
- Vigilance/Anticipatory care regarding common psychologic and developmental issues, such as speech delay, incoordination, ADHD, and learning disabilities
- Early educational assessment and interventions may improve developmental outcome.
- Continuous yearly ophthalmologic examinations:
- Goldman visual field perimetry is suggested in those with any question of an optic nerve tumor.
- Some practitioners use yearly visual field testing (by an ophthalmologist) in addition to or as prescreen to MRI scanning.
- BP checks are increasingly important in adolescents and adults with NF.
- Monitoring for the development of tumors, hypertension, and psychologic and developmental disabilities
Neurofibromatosis - bibliography
- American Academy of Pediatrics Committee on Genetics. Health supervision for children with neurofibromatosis. Pediatrics. 1995;96:368–372.
- Gutman DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997;278:51–57.
- North KN, Riccardi V, Samango-Sprouse C, et al. Cognitive function and academic performance in neurofibromatosis 1: Consensus statement from the NF1 Cognitive Disorders Task Force. Neurology. 1997;48:1121–1127.
- Reynolds R, Browning G, Nawroz I, et al. Von Recklinghausen’s neurofibromatosis: Neurofibromatosis type 1. Lancet. 2003;361:1552–1554.
- Rosser T, Packer RJ. Intracranial neoplasms in children with neurofibromatosis 1. J Child Neurol. 2002;17:630–637, 646–651.
Neurofibromatosis - CODES
Neurofibromatosis - icd9
237.70 Neurofibromatosis
Neurofibromatosis - PATIENT TEACHING-MED
- NIH information page: http://www.ninds.nih.gov/disorders/neurofibromatosis/neurofibromatosis.htm
- “NF Inc.”: http://www.nfinc.org/
- Family counseling regarding genetic implications, possible genetic testing using linkage, or, in some cases, mutation testing of the gene neurofibromin
Neurofibromatosis - FAQ
- Q: Can NF develop into cancer?
- A: Most tumors caused by NF are benign and remain benign (even large tumors). In rare cases, they may become malignant.
- Q: My child has NF1. What specialists must he see?
- A: Your child should have yearly checkups with a physician familiar with the issues of NF (could be a family physician, pediatrician, child neurologist, or geneticist) who will know when to refer to other specialists. Otherwise, periodic visits to an ophthalmologist with experience in NF are the only routine recommendation.
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
More About Neurofibromatosis
More Medical Textbooks Online about Neurofibromatosis
Review other book chapters online related to Neurofibromatosis:
Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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