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Essentials of Diagnosis
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More than six café au lait spots 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals
Two or more neurofibromas of any type or one plexiform neurofibroma
Freckling in the axillary or inguinal regions
Optic glioma
Two or more Lisch nodules (iris hamartomas)
Distinctive bony lesions, such as sphenoid dysplasia or thinning of long bone with or without pseudarthroses
First-degree relative (parent, sibling, offspring) with neurofibromatosis type 1
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General Considerations
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Neurofibromatosis is a multisystem disorder with a prevalence of 1:3000. Fifty percent of cases are due to new mutations in the NF1 gene, which is located on chromosome 17q11.2 encoding neurofibromin. Forty percent of patients develop medical complications over their lifetime. Two or more positive criteria are diagnostic; others may appear over time. Children with six or more café au lait spots and no other positive criteria should be followed; 95% develop neurofibromatosis type 1.
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NF-2 is a dominantly inherited neoplasia syndrome manifested as bilateral vestibular schwannomas (VIII nerve tumors), which may appear in childhood (with loss of hearing, etc). In 50% of patients, the mutation occurs de novo (neither parent carrying the faulty gene).
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The most common presenting symptoms are cognitive or psychomotor problems; 40% have learning disabilities, and 8% have intellectual disability. The history should focus on lumps or masses causing disfigurement, functional problems, or pain. Café au lait spots are seen in most affected children by age 1 year. The typical skin lesion is 10–30 mm, ovoid, and smooth-bordered. Discrete well demarcated neurofibromas or lipomas can occur at any age. Plexiform neurofibromas are diffuse and can invade normal tissue. They are congenital and are frequently detected during periods of rapid growth. If the face or a limb is involved, there may be associated hypertrophy or overgrowth.
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Clinicians should evaluate head circumference, blood pressure, vision, hearing, spine for scoliosis, and limbs for pseudarthroses. Strabismus or amblyopia dictates a search for optic glioma, a common tumor in neurofibromatosis. The eye examination should include a check for proptosis and iris Lisch nodules. The optic disk should be examined for atrophy or papilledema. Any progressive or new neurologic deficit calls for studies to rule out tumor of the spinal cord or CNS. Short stature and precocious puberty are occasional findings.
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Parents should be examined in detail. Family history is important in identifying dominant gene manifestations.
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NF-2 is a dominantly inherited neoplasia syndrome manifested as bilateral vestibular schwannomas (VIII nerve tumors), which may appear in childhood (with loss of hearing, etc). In 50% of patients, the mutation occurs de novo (neither parent carrying the faulty gene). Tumors of cranial nerve VIII (schwannomas) virtually never occur in neurofibromatosis ...