Make the Diagnosis

Make the Diagnosis - February 2018

Courtesy Dr. Parteek Singla and Dr. Donna Bilu Martin
A 64-year-old female presented for a routine full body skin exam. On examination, multiple flesh colored papules were present on her trunk, arms, and legs. The lesions have been present since childhood. She also had multiple café au-lait macules and hyperpigmented macules in the axilla. Her mother had similar lesions on her skin.

Make the diagnosis

Tuberous sclerosis

Neurofibromatosis type I

Neurofibromatosis type II

McCune-Albright Syndrome

Neurofibromatosis (NF) is an autosomal dominant genetic neurocutaneous disorder. There are eight subtypes of NF: NF type 1-7 and NF-NOS, or not otherwise specified. Neurofibromatosis type 1 (NF-1), or von Recklinghausen disease, is the most common and is a result of a genetic mutation on chromosome 17 that is involved in producing a protein called neurofibromin. Neurofibromin is a tumor suppressor that suppresses products of ras proto-oncogenes. When it is absent, tumor progression may occur.

Courtesy Dr. Parteek Singla and Dr. Donna Bilu Martin

Von Recklinghausen NF-1 appears in childhood, usually by age 10. Diagnosis requires the presence of at least 2 of the following 7 criteria:
•Six or more café au lait macules measuring 5 mm in diameter or greater in prepubertal children and measuring greater than 15 mm in postpubertal children.
•Axillary or inguinal freckling (Crowe’s sign).
•Two or more neurofibromas or one plexiform neurofibroma.
•Optic nerve glioma.
•Two or more iris hamartomas (Lisch nodules).
•Sphenoid dysplasia or long-bone abnormalities, such as pseudoarthrosis.
•First degree relative with NF-1.

The diagnosis is usually made via physical examination. Supportive tests include an ophthalmologic exam to detect Lisch nodules and cataracts. A neurological evaluation is essential. Imaging examinations can identify bony abnormalities and tumor growths. Also, genetic testing to identify genetic mutations can be performed.

Dr. Donna Bilu Martin
Patients may develop tumors (malignant peripheral nerve sheath tumors, pheochromocytomas, central nervous system tumors), seizures, learning difficulties, scoliosis, and juvenile chronic myelogenous leukemia. Hypertension may result from renal artery stenosis or pheochromocytomas. As a result, individuals with NF-1 require regular follow up to assess for plexiform neurofibromas, evaluate blood pressure, growth, skeletal changes, learning development, and eye exams. Age appropriate cancer screening is highly recommended.

Neurofibromatosis type 2 results from a genetic mutation located on chromosome 22 that produces a protein called merlin and occurs in adolescence. Acoustic or vestibular neuromas may occur; these interfere with the transmission of sound and maintaining balance. Symptoms include gradual hearing loss, tinnitus, poor balance, and headaches. Radiosurgery and cochlear implants have shown a role for symptomatic treatment in patients with NF-2.

This case and photo were submitted by Parteek Singla, MD, of the division of dermatology at Washington University and Barnes Jewish Hospital, both in St. Louis, and by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at To submit a case for possible publication, send an email to [email protected]

Next Article: