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.
Neurofibromatosis (NF) is an autosomal dominant disorder characterized
by café au lait spots and tumors of the nervous system.
NF has seven recognized subtypes:
1. NF-1: von Recklinghausen disease, mutation in NF1 gene, abnormal
2. NF-2: Acoustic neuroma, mutation in NF2 gene abnormal merlin/neurofibromin2.
6. NF-6: Café au lait macules (CALMs) only.
Synonym von Recklinghausen disease.
Age Birth: plexiform neurofibromas.
Aging from 2 to 3 years: CALM, freckling. Puberty: other neurofibromas.
Incidence NF-1, 1:3000 people;
NF-2, 1:50000 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 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.
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,
CALMs 2-mm to > 20-cm-brown macules
(90%) (Fig. 13-1).
Neurofibromatosis, café au
lait macules Scattered, well-demarcated uniform brown macules
>5 mm on the trunk of an infant with neurofibromatosis.
Crowe’s Sign Frecklelike
macules in the axillary or inguinal folds (80%) (Fig. 13-2).
sign Axillary freckling in an infant with neurofibromatosis.
Neurofibromas Tan nodules with “button
hole sign”—invagination with the tip of finger
(60%–90%) (Fig. 13-3).
Neurofibromatosis, neurofibromas Skin-colored
soft papules and nodules on the back are neurofibromata appearing
in late adolescence in a patient with neurofibromatosis.