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22
Pediatric Neurocutaneous Disorders
NEUROFIBROMATOSIS 207
Neurofibromatosis
Vignette
A 15-year-old boy from Santo Domingo has com- plained of bifrontal headache and intermittent vom- iting for one month. His past medical history is sig- nificant for generalized seizures since the age of 12 months. His developmental history is normal. On examination, several hyperpigmented spots, skin- fold axillary freckling, and subcutaneous nodules are noted. He is alert and cooperative. Fundu- scopic examination shows absent venous pulsa- tions. Bilateral horizontal nystagmus, left dysme- tria, and wide-based gait are also noted.
Summary A 15-year-old boy with headache and inter- mittent vomiting for one month. Past medical history is significant for generalized seizures since 12 months of age. The neurological examination shows absent venous pulsation on funduscopic examination, left dysmetria, and gait ataxia. Also, neurocutaneous findings, hyperpig- mented spots, axillary freckling, and subcutaneous nod- ules are described.
Localization and Differential Diagnosis
The clinical findings indicate signs of increased intracra- nial pressure as well as signs of left cerebellar dysfunc- tion. There is also a long-standing history of generalized convulsions, which point to a cortical irritative process.
An important finding in the vignette is the description of the cutaneous lesions, which are represented by hyper- pigmented macules, skinfold freckling, and subcutaneous nodules. All these features point to a neurocutaneous disorder.
Neurocutaneous syndromes include disorders charac- terized by cutaneous and neurological manifestations.
The major neurocutaneous syndromes include
• Neurofibromatosis (Von Recklinghausen’s disease).
• Tuberous sclerosis.
• Sturge-Weber syndrome.
• Von Hippel-Lindau syndrome.
• Ataxia-telangiectasia.
In this vignette, the clinical findings described suggest the diagnosis of neurofibromatosis (NF). The cutaneous manifestations are characteristic and the signs of cere- bellar dysfunction may indicate the possibility of an in- tracranial tumor. Hyperpigmented macules (“cafe´ au lait spots”) are an important cutaneous feature of neurofibro- matosis type 1, which is the most common type, but are nonspecific and can be observed in other neurocutaneous syndromes and less frequently in neurofibromatosis type 2. Skinfold freckling is usually seen in the axillary and inguinal area. Subcutaneous neurofibromas as well as plexiform neurofibromas are also common manifes- tations of NF type 1.
Intracranial, spinal, and peripheral nerve tumors can complicate NF type 1 but are more common in the type 2. Unilateral or bilateral optic nerve glioma is considered the most commonly observed in NF type 1.
Clinical Features
There are two distinct types of neurofibromatosis: type 1 and type 2. Neurofibromatosis type 1 (NF1), or Von Recklinghausen disease, is the most common form af- fecting 1 in 4000 to 5000 individuals (Menkes and Maria) and resulting from a spontaneous mutation in almost 50 percent of the cases. The cutaneous manifestations char- acteristic of NF1 include cafe´ au lait spots, skinfold freck- ling, and neurofibromas. Cafe´ au lait spots are character- ized by hyperpigmented macules widely distributed over the body, manifesting at birth and clearly obvious during the first year of life. According to the diagnostic criteria, at least six or more cafe´ au lait spots greater than 5 mm in diameter need to be present in prepubertal children and greater than 15 mm in postpubertal patients (Robertson).
208 22. Pediatric Neurocutaneous Disorders
Skinfold freckling consists of small pigmented lesions, usually noted in the areas not exposed to the sun, such as the axillary, inguinal area, inferior part of the chin, and so on.
Neurofibromas, which can be dermal or subcutaneous, are benign tumors that originate from peripheral nerves and tend to increase after puberty. They vary in size and number and can cause nerve compression with pain and loss of function. Plexiform neurofibromas can affect the trunk, face, and neck and cause significant deformity.
Lisch nodules are pigmented hamartomas of the iris and are usually asymptomatic.
The neurological manifestations of NF1 include the possible occurrence of tumors, particularly involving the brain, spinal cord, and peripheral nerves. Among the cen- tral nervous system tumors, optic nerve glioma is the most commonly found in NF1 and may manifest with progressive visual loss and optic atrophy.
Meningiomas, ependymomas and astrocytomas can also be discovered in NF1. Skeletal abnormalities include bone dysplasia of the sphenoid wing of the temporal bone and pseudoarthrosis of the tibia.
Diagnosis
Neurofibromatosis is a hereditary disorder transmitted with an autosomal dominant trait. The gene for NF1 is linked on the long arm of chromosome 17 (17g11.2) that of NF2 is on the long arm of chromosome 22 (22g11.2).
Several criteria have been established in order to fulfill the diagnosis of NF1. They include
• Six or more “cafe´ au lait spots” greater than 5 mm in diameter in prepubertal children and greater than 15 mm in postpubertal patients.
• Two or more neurofibromas of any type or one plexi- form neurofibroma.
• Axillary or inguinal freckling.
• Two or more iris hamartomas (Lisch nodules).
• Optic glioma.
• Typical osseous lesions, such as sphenoid dysplasia or tibial pseudoarthrosis.
• One or more first-degree relatives with NF1.
For NF2, any of the following:
• Bilateral vestibular schwannomas seen with imaging techniques.
• Unilateral vestibular schwannoma in association with any two of the following: meningioma, neurofibroma, schwannoma, and juvenile posterior subcapsular len- ticular opacity.
• Unilateral eighth nerve tumor or other spinal or brain tumor in first-degree relative.
Neurofibromatosis type 2, which is less common than type 1, is characterized by less consistent cutaneous man- ifestations than type 1 and the typical occurrence of bi- lateral vestibular schwannomas. Symptoms include hear- ing loss, tinnitus, headache, and vertigo. Meningiomas of the brain and spine can also occur.
References
Aicardi, J. Diseases of the nervous system in childhood.
McKeith Press. 1992. 203–11.
Berg, B.D. Child neurology: a clinical manual. Second ed.
Philadelphia: J.B. Lippincott Co. 1994. Ch. 9: 185–95.
Brett, E.M. Paediatric neurology. Second ed. New York: Chur- chill Livingstone. 1991.
Conneally, M., Bird, T.D. et al. Neurocutaneous syndromes in Neurogenetics Continuum Part A program of the American Academy of Neurology Vol. 6, No. 6, Dec. 2000.
35–58.
Gutman, D.H. The diagnosis and management of neurofibro- matosis 1. The neurologist. Nov. 1998; Vol. 4: 313–38.
Mackool, B.T. and Fitzpatrick, T.B. Diagnosis of neurofibro- matosis by cutaneous examination. Semin. Neurol. 1992; Vol.
12: 358–63.
Menkes, J.H. and Maria, B.L. Neurocutaneous syndromes in child neurology. Menkes, J.H. and Sarnat, H.B. Sixth ed., Philadelphia: Lippincott Williams & Wilkins 2000. Ch 11:
859–884.
Roach, E.S. Diagnosis and management of neurocutaneous syn- dromes. Semin. Neurol. 1988; Vol. 8: 83–96.
Robertson P. Neurofibromatosis type 1; Neurofibromatosis type 2, Medlink Arbor-Publishing Corp. 1993–2001.
