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The neurocutaneous disorders are a group of inherited conditions associated with skin, CNS, and other systemic abnormalities. Embryologically, the skin and nervous system are derived from the same neural crest origin, and thus it is not surprising that many neurologic disorders have associated skin abnormalities.

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Neurofibromatosis (NF) is an autosomal dominant disorder characterized by café au lait spots and tumors of the nervous system.

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NF has seven recognized subtypes:

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1. NF-1: von Recklinghausen disease, mutation in NF1 gene, abnormal neurofibromin.

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2. NF-2: Acoustic neuroma, mutation in NF2 gene abnormal merlin/neurofibromin2.

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3. NF-3: Mixed NF.

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4. NF-4: Variant NF.

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5. NF-5: Segmental NF.

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6. NF-6: Café au lait macules (CALMs) only.

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7. NF-7: Late-onset NF.

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Synonym von Recklinghausen disease.

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Epidemiology

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Age Birth: plexiform neurofibromas. Aging from 2 to 3 years: CALM, freckling. Puberty: other neurofibromas.

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Gender M > F.

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Race All races.

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Incidence NF-1, 1:3000 people; NF-2, 1:50000 people.

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Heredity AD, with variable expressivity.

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Pathophysiology

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NF-1 is an autosomal dominantly inherited disorder caused by a mutation in chromosome 17q11.2. The gene product, “neurofibromin,” negatively regulates the ras-family of signal molecules through GTP activating protein (GAP) function. NF-2 is an autosomal dominantly inherited disorder caused by a mutation in chromosome 22q12.2. The gene product, “merlin,” is thought to be involved in actin cytoskeletal signaling.

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History

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CALMs are not usually present at birth but appear during the first 3 years; neurofibromas appear during late adolescence and may be tender to palpation. Clinical manifestations can vary depending on which organ is affected: hypertensive headache (pheochromocytomas), pathologic fractures (bone cysts), mental retardation, brain tumor (astrocytoma), short stature, precocious puberty (early menses, clitoral hypertrophy).

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Physical Examination

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Skin Findings

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CALMs 2-mm to > 20-cm-brown macules (90%) (Fig. 13-1).

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FIGURE 13-1
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Neurofibromatosis, café au lait macules Scattered, well-demarcated uniform brown macules >5 mm on the trunk of an infant with neurofibromatosis.

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Crowe’s Sign Frecklelike macules in the axillary or inguinal folds (80%) (Fig. 13-2).

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FIGURE 13-2
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Neurofibromatosis, Crowe’s sign Axillary freckling in an infant with neurofibromatosis.

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Neurofibromas Tan nodules with “button hole sign”—invagination with the tip of finger (60%–90%) (Fig. 13-3).

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FIGURE 13-3
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Neurofibromatosis, neurofibromas Skin-colored soft papules and nodules on the back are neurofibromata appearing in late adolescence in a patient ...

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