The neurocutaneous disorders are a group of inherited conditions associated with skin, peripheral and central nervous system (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.
Neurofibromatosis (NF) is an autosomal dominant disorder characterized cutaneously by café au lait macules (CALMs), axillary freckling, cutaneous neurofibromas, and tumors of the nervous system.
NF has seven recognized subtypes:
NF-1: von Recklinghausen disease, mutation in NF1 gene, abnormal neurofibromin.
NF-2: Acoustic neuroma, mutation in NF2 gene abnormal merlin/neurofibromin 2.
NF-3: Mixed NF with central and peripheral neurofibromas.
NF-4: Variant NF.
NF-5: Segmental NF.
NF-6: CALMs only.
NF-7: Late-onset NF.
SYNONYM von Recklinghausen disease (NF Type 1).
AGE Birth: plexiform neurofibromas may be present (25%). Aging from 2 to 3 years: CALM (>90%), axillary or inguinal freckling (80%). Puberty: other cutaneous neurofibromas (up to 90%).
INCIDENCE NF-1, 1:3,000 people; NF-2, 1:40,000 people.
HEREDITY AD, with variable expressivity.
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 signaling molecules through GTP-activating protein (GAP) function. NF-2 is also an autosomal dominantly inherited disorder caused by a mutation in chromosome 22q12.2. The gene product, merlin (also known as neurofibromin 2), is thought to be involved in actin cytoskeletal signaling.
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 tumors (astrocytoma), short stature, or precocious puberty (early menses, clitoral hypertrophy) may develop.
CALMs 2-mm to >20-cm brown “coffee-with-milk” colored macules (90%). Often with an ovoid appearance (Fig. 13-1).
Neurofibromatosis, café au lait macule
Well-demarcated uniform brown macule on the buttock of a patient with neurofibromatosis.
Crowe's Sign Freckle-like macules in the axillary or inguinal folds (80%) (Fig. 13-2).
Neurofibromatosis, Crowe's sign
Axillary freckling in an adolescent with neurofibromatosis.
NEUROFIBROMAS Soft tan-to-pink nodules with “button hole sign”—invagination with the tip of finger (60–90%) (Fig. 13-3). Occasionally may be subcutaneous, below the surface of the skin.
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