Discussion
Neurofibromatosis (NF) is an autosomal dominant disorder, probably of neural crest origin, that affects all 3 germinal layers; therefore, it can involve any organ system. NF describes at least 2
distinct disorders with overlapping features, but they are actually 2 different clinical entities. Neurofibromatosis-1 (NF-1) or von Recklinghausen disease is more common (1/3,000) than
neurofibromatosis-2 (NF-2), also known as central neurofibromatosis (1/50,000). Patients with NF-2 have few dermatological findings, but they have a high incidence of meningiomas and acoustic
neuromas. Neurofibromatosis type 1 and 2, tuberous sclerosis, Sturge-Weber, and Von Hippel-Lindau disease, are members of the phakomatoses or neurocutaneous syndromes, all of which have both
neurologic and dermatologic lesions. The manifestations of NF-1 result from a mutation in the NF-1 gene, which is mapped to chromosome 17q11.2. Nearly 50% of cases are attributed to new mutations.
The gene product neurofibromin serves as a tumor suppressor and the decreased production of this protein results in a plethora of clinical features. A variety of problems may be present in childhood,
including seizures and intellectual compromise, optic and acoustic involvement, intracranial and spinal tumors, osseous defects and congenital dislocations, oral pathology, endocrine disorders,
autonomic involvement, GI tract involvement, hypertension, and vascular anomalies. NF-1 represents a major risk factor for development of malignancy, particularly malignant peripheral nerve sheath
tumors (MPNST), optic gliomas, other gliomas, and leukemias.The diagnosis of NF-1 presupposes the presence of at least two of the criteria (see Table 1), according to the National Institutes of
Health (NIH) Consensus Development Conference. Plain radiographs could show scoliosis, hypoplastic posterior elements, scalloped vertebrae, dysplastic sphenoid wing, ribbon ribs, multiple
pseudarthroses, enlarged superior orbital fissure.A head CT scan may reveal enlarged optic foramina and fissures or foramen ovale, sphenoid wing dysplasia, lambdoid suture defect and dural
calcifications. Frequent findings in brain MRI represent foci of abnormal signal intensity (FASI) also known as unidentified bright objects (UBO), plexiform neurofibromas and optic nerve gliomas.
FASI usually are located in the basal ganglia, cerebellum and subcortical white matter and show high signal in T2, FLAIR and ADC.MRS can be useful to assess cognitive impairment, distinguish focal
lesions or follow disease progression. The analysis of both frontoparietal lobes using multivoxel proton MRS may show reduction of choline on the right hemisphere, directly related to cognitive
impairment. Single-voxel MRS of a focal lesion tends to show Cho/Cr ratio less than 1.5 in hamartomas (FASI) and more than 2 in gliomas while ratios between 1.5-2 reflect transitional spectrums. FASI
are classed as hamartomas but are probably demyelinating lesions. FASI are transient nonenchancing lesions of childhood and must beware someone if they are persistent, tumefactive or enchancing
lesions. The NF-1 differential diagnosis should includes other disorders of the NF spectrum as NF-2, mosaic NF-1 or NF-2, hereditary spinal NF, familial intestinal NF, autosomal dominant
café-au-lait spots, autosomal dominant neurofibromas. However the FASI differential diagnosis includes demyelination MS lesions, ADEM and if FASI are extensive includes also gliomatosis
cerebri.
