Answer

Neurofibromatosis: Neurofibromatosis (NF) is an autosomal dominant disorder

with numerous presentations affecting nearly every organ system. The 2 major
subtypes are NF type 1 (NF1), also known as peripheral NF, and NF type 2
(NF2), referred to as central NF. However, these terms are not completely correct
because NF1 may cause central characteristics.
About 50% of cases of NF are familial, and the other 50% are due to
spontaneous gene mutation. NF1, also known as von Recklinghausen disease, is
a common genetic disorder involving a gene mutation on chromosome 17 that
affects 1 in every 3000-4000 births (Children's Tumor Foundation, 2006). This
disorder affects all races and both sexes equally (Neurofibromatosis, Inc, 2006).
The diagnosis of NF1 requires that the patient present with 2 or more of the
following conditions: 6 or more caf au lait spots (irregularly shaped, evenly
pigmented, brown macules), 2 or more neurofibromas, axillary or inguinal
freckling, Lisch nodules on the iris, optic glioma, various types of osseous
lesions, or a first-degree relative with the condition.
Symptomatic NF1 typically manifests as flesh-colored, benign skin tumors that
appear late in childhood. The patient may have as few as 3 or as many as
thousands of these benign lesions, which consist of Schwann cells, neural
fibroblasts, mast cells, and vascular elements. Neurofibromas may occur
anywhere in the body and potentially lead to marked disfigurement. Lesions
along visual, auditory, or CNS nerve pathways may result in blindness, deafness,
or neurologic deficits. Other findings associated with this condition include
skeletal anomalies, such as fibrous dysplasia, subperiosteal bone cysts, or
vertebral scalloping (Neurofibromatosis, Inc, 2006).
NF2 is a progressive genetic disorder affecting 1 in every 33,000-40,000 births
(Neurofibromatosis, Inc, 2006). Patients with NF2, which results from an
abnormality of chromosome 22, typically present with acoustic neuromas or
vestibular schwannomas. Clinical manifestations include tinnitus, balance
disorders, and progressive hearing loss. Affected patients may also have
meningiomas and juvenile cataracts. The diagnosis is based on a history of the
condition in a first-degree relative and on any 2 of the conditions listed above for
NF1 (Neurofibromatosis, Inc, 2006).
For both NF1 and NF2, the diagnosis is primarily based on physical findings and
a positive family history. Diagnostic tests that may be useful include radiographic
studies, such as CT of the brain, genetic analysis, and psychological or
developmental assessment.
No cure exists for this condition. Recommendations for follow-up include referral
to support groups, psychological counseling, evaluation of learning disorders,
surgical excision of lesions, and regular monitoring by a primary care provider for
any changes that may occur, as patients with NF1 are at somewhat increased
risk of malignancy. Annual ocular examinations are recommended. Genetic
testing is also advocated in patients with NF who wish to have children. Surgery
has been a successful treatment for the lesions themselves; however, recurrence
often occurs, and nerve damage is a risk when tumors are located along neural
pathways (National Institute of Neurologic Disorders and Stroke, 2006).
For more information on neurofibromatosis, see the eMedicine articles
Neurofibromatosis (within the Dermatology specialty), Neurofibromatosis, Type 1

and Neurofibromatosis, Type 2 (within the Neurology specialty), and

Neurofibromatosis Type 1 and Neurofibromatosis Type 2 (within the Radiology
specialty). For other resources and access to support networks, contact the Web
pages of Children's Tumor Foundation and Neurofibromatosis, Inc.
References
Children's Tumor Foundation: Diagnosis of NF1. Available at:
http://www.ctf.org/aboutnf/nf1/diagnosisnf1.htm. Accessed July 29, 2006.
Children's Tumor Foundation: Diagnosis of NF2. Available at:
http://www.ctf.org/aboutnf/nf2/diagnosisnf2.htm. Accessed July 29, 2006.
Neurofibromatosis, Inc: What is NF? Available at:
http://www.nfinc.org/what.shtml. Accessed July 29, 2006.

NINDS: National Institute of Neurologic Disorders and Stroke.

Neurofibromatosis Fact Sheet. Available at:
http://www.ninds.nih.gov/disorders/neurofibromatosis/
detail_neurofibromatosis.htm#57453162. Accessed July 29, 2006.

BACKGROUND
A 32-year-old woman presents to the emergency department with several fleshcolored papules on her face, trunk, and upper extremities. She noticed the
lesions at approximately 10 years of age. However, over the past 5 years, the
lesions have increased in number and become uncomfortable. She primarily
complains of irritation from the lesions along her bra line. She previously
underwent excision of other similar skin lesions 5 years ago, but these have
since recurred. She denies having discharge, pain, trauma, contact with
individuals with atypical skin lesions or rashes, travel out of the country, unusual
exposure to animals, or a history of sexually transmitted disease.
The patient's medical and surgical history includes environmental allergies,
frequent episodes of bronchitis, and the aforementioned excisions. She takes
cetirizine HCl (Zyrtec) and fluticasone propionate (Flonase) for allergies and has
no known drug allergies. Her family history is significant for coronary artery
disease, hypertension, diabetes mellitus, and glaucoma. She does not smoke
and drinks alcohol on occasion. The review of systems is otherwise
noncontributory.
Physical examination reveals dozens of fleshy nodules of 0.5-2.0 cm throughout
her trunk, face, and upper extremities. The nodules are nontender to palpation
and nonerythematous, and they produce no discharge, crusting, or scaling.
Several 1.5- to 3-cm, tan, oval macules and patches with well-defined borders
are located on her trunk and upper extremities (see Images). Her vital signs are
within normal limits, and the rest of the physical findings are unremarkable.
What is the diagnosis?
Hint
Tan macules or patches, known as "caf au lait" spots, are characteristic of this
genetic disorder.

Author:

Alyssa D. Abbey, BA, PA-S,

Physician Assistant Student,
Barry University-Miami Shores,
Fla
Martin I. Newman, MD,
Department of Plastic and
Reconstructive Surgery,
Cleveland Clinic Florida, Weston

eMedicine
Editor:

Erik D. Schraga, MD,

Staff Physician,
Kaiser Permanente,
Santa Clara Medical Center, Calif