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Pathophysiology of Neurofibromatosis Type 1

Amy Theos, MD; and Bruce R. Korf, MD, PhD
[+] Article, Author, and Disclosure Information

From the University of Alabama at Birmingham, Birmingham, Alabama.

Potential Financial Conflicts of Interest: Grants received: B.R. Korf (National Institutes of Health, U.S. Army).

Requests for Single Reprints: Bruce R. Korf, MD, PhD, Department of Genetics, University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294; e-mail, bkorf@uab.edu.

Current Author Addresses: Dr. Theos: Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294.

Dr. Korf: Department of Genetics, University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294.

Ann Intern Med. 2006;144(11):842-849. doi:10.7326/0003-4819-144-11-200606060-00010
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Neurofibromatosis type 1 is a highly variable disorder with signs and symptoms that may begin at birth and evolve over a lifetime. Phenotypic features can be broadly divided into tumors and nontumor manifestations.

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Grahic Jump Location
Figure 1.
Several dermal neurofibromas that are visible as raised lesions but are sometimes first detected by palpation.

The distance between each hash mark is 1 cm.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Angiogram showing renal artery stenosis in a patient with neurofibromatosis type 1.
Grahic Jump Location
Grahic Jump Location
Figure 3.
Skeletal dysplasias in neurofibromatosis type 1.Top.Bottom.

Dysplasia of tibia and fibula. Computed tomography scan showing dysplasia of thoracic vertebra.

Grahic Jump Location
Grahic Jump Location
Figure 4.
Ras signaling pathway.GDPGTP

Binding of ligand to membrane tyrosine kinase receptor results in conversion of Ras–guanosine diphosphate ( ) to Ras–guanosine triphosphate ( ). This leads to a cascade of activation of other proteins (“effector pathways”), which eventually results in activation of transcription of specific genes. Shc, Grb2, SoS, Raf, Mek, and Erk are additional proteins in the Ras signal transduction pathway. NF1 = neurofibromatosis type 1; P = phosphate

Grahic Jump Location
Grahic Jump Location
Figure 5.
Formation of neurofibroma.NF1

A Schwann cell that is heterozygous for an mutation (+/−) undergoes mutation to −/−. This cell proliferates and also attracts other cells, including fibroblasts, perineurial cells, and mast cells, to proliferate in the lesion.

Grahic Jump Location




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