{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:42:03Z","timestamp":1790862123155,"version":"4.1.0"},"reference-count":19,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,8]]},"abstract":"<jats:p>OBJECTIVE: To establish the frequency of minor disease features in children with neurofibromatosis type 1 (NF1) and to evaluate the value of minor disease features in children &lt; or = 6 years with a suspected diagnosis of NF1, considering that the disease is virtually 100% penetrant at 6 years of age. DESIGN: During this 10 year, prospective, multidisciplinary, follow up study, 209 children suspected of having NF1 were examined; 150 were diagnosed with NF1 and 59 were not. The present analysis included children in whom NF1 was considered to be present at 6 years of age (n=85) and children without NF1 at 6 years of age (n=42). RESULTS: The minor disease features macrocephaly (52.9%), short stature (24.7%), hypertelorism (63.5%), and thorax abnormalities (37.6%) were highly prevalent in children with NF1 and significantly associated with a diagnosis of NF1 at 6 years of age. In addition, the mean number of minor disease features was significantly higher in children with NF1 at 6 years of age compared to the group without a diagnosis at 6 years of age (mean 1.8 v 0.8, p&lt;0.001). Moreover, children with three or more minor disease features were all diagnosed with NF1 under the age of 6 years. Multivariate analysis using a logistic regression model showed that macrocephaly, short stature, hypertelorism, and thorax abnormalities were all independently associated with the presence of NF1 at 6 years of age. CONCLUSION: In children with insufficient diagnostic criteria aged &lt; or = 6 years, documentation of minor disease features may be a helpful aid in predicting the diagnosis of NF1 in years to come.<\/jats:p>","DOI":"10.1136\/jmg.35.8.624","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"624-627","source":"Crossref","is-referenced-by-count":38,"title":["Minor disease features in neurofibromatosis type 1 (NF1) and their possible value in diagnosis of NF1 in children &lt; or = 6 years and clinically suspected of having NF1. Neurofibromatosis team of Sophia Children's Hospital."],"prefix":"10.1136","volume":"35","author":[{"given":"M H","family":"Cnossen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K G","family":"Moons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M P","family":"Garssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N M","family":"Pasmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"de Goede-Bolder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M F","family":"Niermeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D E","family":"Grobbee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1998,8,1]]},"reference":[{"key":"ref_1","first-page":"172","article-title":"Health Consensus Development Conference Statement: Neurofibromatosis","volume":"1","author":"National Institutes of","year":"1987","unstructured":"National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. Bethesda, Md, USA, 13-15 July 1987. Neurofibromatosis 1988;1:172-8."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1136\/jmg.26.11.704","article-title":"A genetic study of von Recklinghausen neurofibromatosis in southeast Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity","volume":"26","author":"Huson, S.M.; Compston, D.A.S.; Clark, P.; Harper, P.S.","year":"1989","unstructured":"Huson SM, Compston DAS, Clark P, Harper PS. A genetic study of von Recklinghausen neurofibromatosis in southeast Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 1989;26: 704-11.","journal-title":"J Med Genet"},{"key":"ref_3","first-page":"717","article-title":"The diagnosis of neurofibromatosis-I in the child under the age of 6 years","volume":"143","author":"Obringer, A.C.; Meadows, A.T.; Zackai, E.H.","year":"1989","unstructured":"Obringer AC, Meadows AT, Zackai EH. The diagnosis of neurofibromatosis-I in the child under the age of 6 years. Am 7 Dis Child 1989;143:717-19.","journal-title":"Am 7 Dis Child"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0092-8674(90)90253-B","article-title":"A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations","volume":"62","author":"Cawthon, R.M.; Weiss, R.; Xu, G.F.","year":"1990","unstructured":"Cawthon RM, Weiss R, Xu GF, et al. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 1990;62: 193-201.","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0092-8674(90)90252-A","article-title":"Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus","volume":"62","author":"Viskochil, D.; Buchberg, A.M.; Xu, G.","year":"1990","unstructured":"Viskochil D, Buchberg AM, Xu G, et al. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 1990;62:187-92.","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1126\/science.2134734","article-title":"Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NFl-patients","volume":"249","author":"Wallace, M.R.; Marchuk, D.A.; Andersen, L.B.","year":"1990","unstructured":"Wallace MR, Marchuk DA, Andersen LB, et al. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NFl-patients. Science 1990;249:181-6.","journal-title":"Science"},{"key":"ref_7","first-page":"83101","article-title":"Molecular basis of neurofibromatosis type 1 (NFl): mutation analysis and polymorphisms in the NFl gene","volume":"4","author":"Upadhyaya, M.; Shaw, D.J.; Harper, P.S.","year":"1994","unstructured":"Upadhyaya M, Shaw DJ, Harper PS. Molecular basis of neurofibromatosis type 1 (NFl): mutation analysis and polymorphisms in the NFl gene. Hum Mutat 1994;4:83101.","journal-title":"Hum Mutat"},{"key":"ref_8","article-title":"The neurofibromatoses: a pathogenetic and clinical overview","author":"Huson, S.M.","year":"1994","unstructured":"Huson SM, Hughes RAC, eds. The neurofibromatoses: a pathogenetic and clinical overview. London: Chapman and Hall, 1994."},{"key":"ref_9","article-title":"A prospective 10 year follow-up study of patients with neurofibromatosis type 1 (NF1)","author":"Cnossen, M.H.; Van den Broek, K.M.; Waasdorp, C.M.E.","unstructured":"Cnossen MH, Van den Broek KM, Waasdorp CME, et al. A prospective 10 year follow-up study of patients with neurofibromatosis type 1 (NF1). Arch Dis Child (in press).","journal-title":"Arch Dis Child"},{"key":"ref_10","first-page":"482","article-title":"Diagnostic delay in neurofibromatosis type 1","volume":"156","author":"Cnossen, M.H.; Smit, F.J.; de Goede-Bolder, A.; Frets, P.G.; Duivenvoorden, H.J.; Niermeijer, M.F.","year":"1997","unstructured":"Cnossen MH, Smit FJ, de Goede-Bolder A, Frets PG, Duivenvoorden HJ, Niermeijer MF. Diagnostic delay in neurofibromatosis type 1. Eur7Pediatr 1997;156:482-7."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1542\/peds.90.6.924","article-title":"Diagnostic outcome in children with multiple cafe au lait spots","volume":"90","author":"Korf, B.R.","year":"1992","unstructured":"Korf BR. Diagnostic outcome in children with multiple cafe au lait spots. Pediatrics 1992;90:924-7.","journal-title":"Pediatrics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1136\/jmg.26.11.712","article-title":"A genetic study of von Recklinghausen neurofibromatosis in south-east Wales. II. Guidelines for genetic counselling","volume":"26","author":"Huson, S.M.; Compston, D.A.S.; Harper, P.S.","year":"1989","unstructured":"Huson SM, Compston DAS, Harper PS. A genetic study of von Recklinghausen neurofibromatosis in south-east Wales. II. Guidelines for genetic counselling. Jf Med Genet 1989;26:712-21.","journal-title":"Jf Med Genet"},{"key":"ref_13","article-title":"Neurofibromatosis: phenotype, natural history and pathogenesis","author":"Riccardi, V.M.","year":"1992","unstructured":"Riccardi VM. Neurofibromatosis: phenotype, natural history and pathogenesis. 2nd ed. Baltimore: The John Hopkins University Press, 1992.","edition":"2nd ed"},{"key":"ref_14","article-title":"Measurement of body proportions in children. The Oosterwolde study","author":"Gerver, W.J.M.","year":"1988","unstructured":"Gerver WJM. Measurement of body proportions in children. The Oosterwolde study, Groningen University, 1988."},{"key":"ref_15","first-page":"284","article-title":"Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants","volume":"42","author":"Riccardi, V.M.; Lewis, R.A.","year":"1988","unstructured":"Riccardi VM, Lewis RA. Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants. Am 7 Hum Genet 1988;42:284-9.","journal-title":"Am 7 Hum Genet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1056\/NEJM199411243312102","article-title":"Neurofibromatosis type 1 due to germ-line mosaicism in a clinically normal father","volume":"331","author":"Lazaro, C.; Ravella, A.; Gaona, A.; Volpini, V.; Estivill, X.","year":"1994","unstructured":"Lazaro C, Ravella A, Gaona A, Volpini V, Estivill X. Neurofibromatosis type 1 due to germ-line mosaicism in a clinically normal father. N EnglJfMed 1994;331:1403-7.","journal-title":"N EnglJfMed"},{"key":"ref_17","first-page":"484","article-title":"Somatic mosaicism in a patient with neurofibromatosis type 1","volume":"58","author":"Colman, S.D.; Rasmussen, S.A.; Ho, V.T.; Abernathy, C.R.; Wallace, M.R.","year":"1996","unstructured":"Colman SD, Rasmussen SA, Ho VT, Abernathy CR, Wallace MR. Somatic mosaicism in a patient with neurofibromatosis type 1. Am 7 Hum Genet 1996;58:484-90.","journal-title":"Am 7 Hum Genet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s004390050341","article-title":"Somatic mosaicism for deletion of the entire NFl gene identified by FISH","volume":"99","author":"Wu, B.L.; Boles, R.G.; Yaari, H.; Weremowicz, S.; Schneider, G.H.; Korf, B.R.","year":"1997","unstructured":"Wu BL, Boles RG, Yaari H, Weremowicz S, Schneider GH, Korf BR. Somatic mosaicism for deletion of the entire NFl gene identified by FISH. Hum Genet 1997;99:209-13.","journal-title":"Hum Genet"},{"key":"ref_19","first-page":"305","article-title":"An analysis of variation in expression of neurofibromatosis (NF) type 1 (NFl): evidence for modifying genes","volume":"53","author":"Easton, D.F.; Ponder, M.A.; Huson, S.M.; Ponder, B.A.","year":"1993","unstructured":"Easton DF, Ponder MA, Huson SM, Ponder BA. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NFl): evidence for modifying genes. 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