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Causes of Neurofibromatosis Type 1 (NF1) on Female Pts Ages 3 to 10

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Historically, there has been confusion regarding the relationship between neurofibromatosis types 1 and 2. It was initially thought that these two conditions represented different manifestations of the same underlying entity. In 1930, Garner and Frazier first suggested that individuals with only central nervous system tumors should be differentiated from those with other manifestations of the condition.

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Neurofibromatosis 1 (NF1), also called von Recklinghausen's disease, is a genetic disorder characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormal skin color (pigmentation)

Areas of abnormal skin pigmentation typically include pale tan or light brown discolorations (cafe-au-lait spots), freckling in atypical locations such as under the arms (axillary region) or in the groin (inguinal region). Such abnormalities of skin pigmentation are often evident by one year of age and tend to increase in size and number over time.At birth or early childhood, affected individuals may have relatively large, benign tumors that consist of bundles of nerves and other tissue (plexiform neurofibromas). Individuals with NF1 may also develop benign nodules on the colored regions of the eyes (Lisch nodules), or tumors in the nerves of the visual pathway (optic pathway gliomas). More rarely, affected individuals may develop certain malignant (cancerous) tumors. NF1 may also be characterized by an unusually large head size (macrocephaly) and relatively short stature. Additional abnormalities may also be present, such as episodes of uncontrolled electrical activity in the brain (seizures); learning disabilities, and attention deficits; speech difficulties; abnormally increased activity (hyperactivity); and skeletal malformations, including progressive curvature of the spine (scoliosis), bowing of the lower legs (pseudoarthrosis), and improper development of certain bones. Associated symptoms and findings may vary greatly in range and severity from person to person, even within the same family. Most people with NF1 have normal intelligence but learning disabilities appear in about 50% of children with NF1.

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In the same 1982 report, pseudoatrophic macules were described as oval, slightly depressed lesions ranging in size from 5 – 10 cm

Skin texture and color were similar relative to surrounding skin, although upon palpation the lesions were “softer” and showed a loss of underlying subcutaneous tissue. Histologic examination showed a reduction in collagen in the reticular dermis and increased perivascularly-situated neuroid tissue with Schwann cells and fibroblasts. Another case report from 1996 had similar clinical features; histologic examination revealed replacement of collagen bundles with neuroid tissue, consisting of neoplastic cells with oval/spindle nucleir. Norris et al. examined the ultrastructure of biopsies of these lesions (they referred to them as neurofibromatous dermal hypoplasia or NDH) as well as the response to several vasodilators and a vasoconstrictor. Histologic examination showed loose whorls of neurofibromatous tissue intermingled with collagen fibers surrounding both nerve trunks and small blood vessels; the primary cell type was the perineurial cell (Piqué E, Olivares M, 1996). Further, the authors postulated that the cuff of cells surrounding the vessels acted as both a physical splint and diffusion barrier because the pseudo-atrophic macules did not respond with a wheal and flare response to vasodilators (Norris JF, Smith AG, 1985).

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In the end, luckily, there has been lots of research into how kids with different kinds of learning disabilities can learn best

Your child’s IEP team will work with you to develop a plan that’s been customized for her, but adjustments that the school might make could include giving your child extra time on tests assigning a tutor to work with her having her sit closer to the front of the room. Like all children, kids with NF1 have strengths and weaknesses; and like all children, helping them succeed is just a matter of capitalizing on their strengths and compensating for their weaknesses.

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Piqué E, Olivares M, Fariña MC, Martin L, Sarasa JL, Campos JM, et al. Pseudoatrophic Macules: A Variant of Neurofibroma. Cutis. 1996;57:100–2.

Norris JF, Smith AG, Fletcher PJ, Marshall TL, Hand MJ. Neurofibromatous dermal hypoplasia: a clinical, pharmacological and ultrastructural study. Br J Dermatol. 1985;112:435–41.

Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumors in neurofibromatosis 1. J Med Genet. 2002

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