The diagnostic criteria, associated problems, genetics, pathogenesis, clinical evaluation and treatment of neurofibromatosis type I in childhood are reviewed from the Department of Pediatrics, Northwestern University Medical School and Children's Memorial Hospital, Chicago, Illinois. The National Institutes of Health Consensus Development Conference identified seven components of the syndrome, two or more required for the diagnosis: 1) six or more cafe au lait macules, 2) two or more neurofibromas or one plexiform neurofibroma, 3) freckling in axillary or inguinal region, 4) optic glioma, 5) two or more Lisch nodules, 6) osseous lesion such as sphenoid dysplasia or pseudoarthrosis and 7) a first degree relative with NF-1. Other malignancies that occur in association with NF-1 include neurofibrosacroma, leukemia, xanthogranulomas, neuroblastoma, rhabdomyosarcoma and Wilms tumor. The full scale IQ is relatively low, but usually within the normal range. A visual perceptual disability occurs in 60 to 90% of the patients. The degree of intellectual deficit increases in direct proportion to the clinical severity. NF-1 and the Noonan syndrome may occur together. The localization of the NF-1 gene to chromosome 17 and the identification of linked markers has opened the door to prenatal and presymptomatic diagnosis of NF-1 and linkage analysis will soon be possible in families in which there are two or more affected members. Nearly 50% of persons with NF-1 do not have an affected parent and 50% are new mutations. Neurocristopathy, a generalized disorder of cells of neural crest origin, is the hypothesis for pathogenesis of NF-1. Histamine containing mast cells are found in high concentrations in peripheral neurofibromas and may be a factor in promotion of neurofibroma growth.

Screening for optic gliomas by MRI is justified because of a high incidence (15%). Radiation therapy is the standard approach for optic glioma in children older than 5 years. Adverse effects include hypopituitarism, growth failure, cognitive deterioration, cataracts and secondary malignancies. Chemotherapy, if proven effective, would be preferable. Many optic gliomas are nonprogressive. Hormone treatment for precocious puberty associated with optic glioma may be efficacious. Related neurofibromatosis syndromes include neurofibromatosis type 2, segmental neurofobromatosis and familial cafe-au-lait spots. Patients with multiple cafe-au-lait spots may not have any of the other stigmata of NF-1. The gene for neurofibromatosis type 2 with bilateral acoustic neurofibromatosis has been linked to chromosome 22. [1]

COMMENT: To this excellent review of NF-1 we may add a note concerning the simultaneous occurrence of neurocutaneous syndromes and a first report of a case of NF-2 and tuberous sclerosis in the same patient.

Neurofibromatosis I and tuberous sclerosis may occur simultaneously. This association is rare and the report by Schull and Crowe [2] is the only case accepted by Gomez M [3]. Two patients reported by Vouge M et al [4] had clinical manifestations of neurofibromatosis I and also subependymal or intranuclear calcifications in the brain identical to the tubers of tuberous sclerosis.

I have recently evaluated a 14 year old girl with the simultaneous occurrence of neurofibromatosis type 2 and tuberous sclerosis. She presented with flaccid weakness and wasting of the left upper limb and electromyographic evidence of brachial plexopathy affecting primarily the upper and middle trunks. Examination of the skin showed a large depigmented patch over the right deltoid region, a small shagreen patch over the left lumbar region and a large pigmented area under the left axilla. The diagnosis of tuberous sclerosis was based on the skin lesions and typical calcifications shown in the CT scan of the head. The child had one seizure within 24 hours of a booster DPT immunization at 18 months. The diagnosis of neurofibromatosis type 2 was suggested by an MRI of the cervical spine showing enlargement of neural foramina C5-6 on the left side and was confirmed by a gadolinium MRI performed by Dr. Gomez at the Mayo Clinic. He also uncovered a right acoustic neuroma and a small meningioma at the level of C1. The weakness and wasting of the left arm was explained by a plexiform neurofibroma. In addition the patient had a familial macular degeneration. She had inherited the neurofibromatosis from her father who had bilateral acoustic neuromas and other neurofibromata. No one in the family was known to suffer from tuberous sclerosis and examination of the mother was negative [5].