Cognitive deficits and academic learning difficulties are the most common neurologic "complication" of neurofibromatosis 1 in childhood and can be responsible for significant lifetime morbidity. There is a slight increase in the frequency of mental retardation (Wechsler Full-Scale IQ < 70) in children with neurofibromatosis 1, but the mean Full-Scale IQ for the patient group is within 1 SD of the population mean. Academic difficulties are common, as are specific deficits in visuospatial ability, executive function, expressive and receptive language, and attentional skills. Behavioral and psychosocial problems have a major impact on quality of life, although there are few objective studies in this area. Current research is focusing on the pathogenesis of the disorder. Clinical studies have identified possible radiologic and pathologic markers for cognitive deficits in neurofibromatosis 1, which can now be explored in animal models. (J Child Neurol 2002;17:605-612).
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References
1.
Gutmann DH: Neurofibromin in the brain. J Child Neurol2002;17: 592-601.
2.
Costa RM, Silva AJ: Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis type 1. J Child Neurol2002;17:622-626.
3.
North KN, Riccardi V., Samango-Sprouse C., et al: Cognitive function and academic performance in neurofibromatosis 1: Consensus statement from the NF1 Cognitive Disorders Task Force. Neurology1997;48:1121-1127.
4.
North KN: Cognitive function and academic performance, in Friedman JM, Gutmann DH, MacCollin M, Riccardi VM (eds): Neurofibromatosis: Phenotype, Natural History, and Pathogenesis, 3rd ed. Baltimore , Johns Hopkins University Press, 1999, 162-189.
5.
Ozonoff S.: Cognitive impairment in neurofibromatosis type 1. Am J Med Genet1999;89:45-52.
6.
Mazzocco MM, Turner JE, Denckla MB, et al: Language and reading deficits associated with neurofibromatosis type 1: Evidence for not so non-verbal learning disability. Dev Neuropsychol1995; 11:503-522.
7.
Eliason MJ: Neurofibromatosis: Implications for learning and behaviour. J Dev Behav Pediatr1986;7:175-179.
8.
Varnhagen CK , Lewin S., Das JP, et al: Neurofibromatosis and psychological processes. J Dev Behav Pediatr1988;9:257-265.
9.
North K., Joy P., Yuille D., et al: Learning difficulties in neurofibromatosis type 1: The significance of MRI abnormalities. Neurology1994;44:878-883.
10.
Wadsby M., Lindenhammer H., Eeeg-Olofsson O.: Neurofibromatosis in childhood: Neuropsychological aspects. Neurofibromatosis1989;2:251-260.
11.
Legius E., Descheemaeker MJ, Spaepen A., et al: Neurofibromatosis type 1 in childhood: A study of the neuropsychological profile in 45 children. Genet Couns1994;5:51-60.
12.
Eldridge R. , Denckla MB, Bien E., et al: Neurofibromatosis type 1 [Recklinghausen's disease]: Neurologic and cognitive assessment with sibling controls. Am J Dis Child1989; 143:833-837.
13.
Hoffman KJ, Harris EL, Bryan RN, Denckla MB: Neurofibromatosis type 1: The cognitive phenotype. J Pediatr1994;124:S1-S8.
14.
Ferner RE, Hughes Rac, Wenman J.: Intellectual impairment in neurofibromatosis 1. J Neurol Sci1996;138:125-133.
15.
Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association, 1994.
16.
Dilts CV, Carey JC, Kircher JC, et al: Children and adolescents with neurofibromatosis 1: A behavioral phenotype. J Dev Behav Pediatr1996; 17:229-239.
17.
Brewer VR, Moore BD3rd, Hiscock M: Learning disability subtypes in children with neurofibromatosis . J Learn Disabil1997;30: 521-533.
Joy P., Roberts C., North K., de Silva M.: Neuropsychological function and MRI abnormalities in neurofibromatosis type 1. Dev Med Child Neurol1995;37:906-914.
20.
Denckla MD, Hoffman K., Mazzocco Mmm, et al: Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower-IQs in children with neurofibromatosis-1. Am J Med Genet1996;67:98-102.
21.
Bawden H., Dooley J., Buckley D., et al: MRI and nonverbal cognitive deficits in children with neurofibromatosis 1. J Clin Exp Neuropsychol1996;18:784-792.
22.
Chapman CA, Waber DP, Bassett N., et al: Neurobehavioral profiles of children with neurofibromatosis 1 referred for learning disabilities are sex-specific. Am J Med Genet1996;67:127-132.
23.
Zoller Met, Rembeck B., Backman L.: Neuropsychological deficits in adults with neurofibromatosis type 1. Acta Neurol Scand1997; 95:225-232.
24.
Kayl AE, Moore BD3rd: Behavioral phenotype of neurofibromatosis, type 1. Mental retardation and developmental disabilities. Ment Retard Dev Disabil Res Rev2000;6:117-124.
25.
Benjamin CM , Colley A., Donnai D., et al: Neurofibromatosis type 1 (NF1): Knowledge, experience, and reproductive decisions of affected patients and families. J Med Genet1993;30:567-574.
26.
Porter-Counterman A., Saylor CF, Pai S.: Psychological adjustment for children and adolescents with neurofibromatosis. Chaldren's Healthcare1996;24:223-234.
27.
Ablon J.: Living with genetic disorder: The impact of neurofibromatosis 1. Westport, CT, Auburn House.
28.
Gresham FM: Social skills and learning disabilities as type III error: Rejoinder to Conte and Andrews. J Learn Disabil1993;26: 154-158.
29.
Achenbach TM: Manual for the Child Behaviour Checklist/4-18 and 1991 Profile. Burlington, VT, Department of Psychiatry, University of Vermont, 1991.
30.
North K., Joy P., Yuille D., et al: Cognitive function and academic performance in children with neurofibromatosis type 1. Dev Med Child Neurol1995;37:427-436.
31.
Samango-Sprouse C., Vezina LG, Brasseux C., et al: Cranial magnetic resonance findings and the neurodevelopmental performance in the young child with neurofibromatosis 1, abstract. Am J Hum Genet1997;61:A35.
32.
Lorch M., Ferner R., Golding J., Whurl R.: The nature of speech and language impairments in adults with neurofibromatosis 1. J Neurolinguist1999;12:157-165.
33.
Moore BD, Slopis JM, Schomer D., et al: Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis. Neurology1996;46:1660-1668.
34.
Moore BD, Slopis JM, Jackson EF, De Winter AE: Brain volume in children with neurofibromatosis type 1: Relation to neuropsychological status. Neurology2000;54:22, 914-926.
35.
Riccardi VM, Eichner JE: Neurofibromatosis: Phenotype, Natural History and Pathogenesis. Baltimore, Johns Hopkins University Press, 1986.
36.
Moore BD, Ater JL, Needle MN, et al: Neuropsychological profile of children with neurofibromatosis, brain tumor or both. J Child Neurol1994;9:368-377.
37.
Rosman NP, Pearce J.: The brain in multiple neurofibromatosis (von Recklinghausen's disease): A suggested neuropathological basis for the associated mental defect. Brain1967;90:829-838.
38.
Rubinstein LJ: The malformative central nervous system lesions in the central and peripheral forms of neurofibromatosis: A neuropathological study of 22 cases. Ann N Y Acad Sci1986;486:14-29.
39.
Nordlund ML , Rizvi TA, Brannan CI, Ratner N.: Neurofibromin expression and astrogliosis in neurofibromatosis (type 1) brains. J Neuropathol Exp Neurol1995;54:588-600.
40.
Bognanno JR , Edwards MK, Lee TA, et al: Cranial MR imaging in neurofibromatosis . AJNR Am J Neuroradiol1988;9:461-468.
41.
Dunn DW, Roos KL: MRI evaluation of learning difficulties and incoordination in neurofibromatosis type 1. Neurofibromatosis1989; 2:1-5.
42.
Pont MS, Elster AD: Lesions of skin and brain: Modem imaging of the neurocutaneous syndromes. AJR Am J RoerztgeraoL1992;158: 1193-1203.
43.
Sevick RJ, Barkovich AJ, Edwards Msb, et al: Evolution of white matter lesions in neurofibromatosis type 1: MR findings. AJR Am J Roentgenol1992;159:171-175.
44.
VanEs S, North K, McHugh K, de Silva M: MRI abnormalities in children with NF1. PaediatrRadiol1996;26:478-487.
45.
Duffner PK, Cohen ME, Seidel FG, Shucard DW: The significance of MRI abnormalities in children with neurofibromatosis. Neurology1989;39:373-378.
46.
Aoki S., Barkovich AJ, Nishimura K., et al: Neurofibromatosis types 1 & 2: Cranial MR findings. Radiology1989;172:527-534.
47.
Itoh T., Magnaldi S., White RM, et al: Neurofibromatosis type 1: The evolution of deep gray and white matter MR abnormalities. AJNR Am J Neuroradiol1994;15:1513-1519.
48.
DiPaolo DP, Zimmerman RA, Rorke LB, et al: Neurofibromatosis type 1: Pathologic substrate of high-signal intensity foci in the brain. Radiology1995 ;195:721-724.
49.
Kaplan AM, Lawson MA, Bonstelle CT, Wodrich DL: Positron emission tomography (PET) in children with NF1, abstract. San Francisco, International Child Neurology Association Conference, 1994.
50.
Balestri P. , Lucignani G., Fois A., et al: Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [ 18F]-2-fluoro-2-deoxy-D-glucose and PET. J Neurol Neurosurg Psychiatry1994;57: 1479-1483.
51.
Castillo M. , Green C., Kwock L., et al: Proton MR spectroscopy in patients with neurofibromatosis type 1: Evolution of hamartomas and clinical correlation . AJNR Am J Neuroradiol1995; 16:141-147.
52.
Cutting LE, Koth CW, Burnette CP, et al: Relationship of cognitive functioning, whole brain volumes, and T2-weighted hyperintensities in neurofibromatosis 1. J Child NeuroL2000;15:157-160.
53.
Said Sma, Yeh T., Greenwood RS, et al: MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis. Neuroreport1996;7:1941-1944.
54.
Ferner RE, Chaudhuri R., Bingham J., et al: MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment. J Neurol Neurosurg Psychiatry1993;56:492-495.
55.
Legius E., Descheemaeker MJ, Steyaert J., et al: Neurofibromatosis type 1 in childhood: Correlation of MRI findings with intelligence. J Neurol Neurosurg Psychiatry1995;59:638-640.
