Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1998 Aug;35(8):624–627. doi: 10.1136/jmg.35.8.624

Minor disease features in neurofibromatosis type 1 (NF1) and their possible value in diagnosis of NF1 in children < or = 6 years and clinically suspected of having NF1. Neurofibromatosis team of Sophia Children's Hospital.

M H Cnossen 1, K G Moons 1, M P Garssen 1, N M Pasmans 1, A de Goede-Bolder 1, M F Niermeijer 1, D E Grobbee 1
PMCID: PMC1051384  PMID: 9719365

Abstract

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 < 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<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 < or = 6 years, documentation of minor disease features may be a helpful aid in predicting the diagnosis of NF1 in years to come.

Full text

PDF
624

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O'Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990 Jul 13;62(1):193–201. doi: 10.1016/0092-8674(90)90253-b. [DOI] [PubMed] [Google Scholar]
  2. Cnossen M. H., Smit F. J., de Goede-Bolder A., Frets P. G., Duivenvoorden H. J., Niermeijer M. F. Diagnostic delay in neurofibromatosis type 1. Eur J Pediatr. 1997 Jun;156(6):482–487. doi: 10.1007/s004310050644. [DOI] [PubMed] [Google Scholar]
  3. Colman S. D., Rasmussen S. A., Ho V. T., Abernathy C. R., Wallace M. R. Somatic mosaicism in a patient with neurofibromatosis type 1. Am J Hum Genet. 1996 Mar;58(3):484–490. [PMC free article] [PubMed] [Google Scholar]
  4. Easton D. F., Ponder M. A., Huson S. M., Ponder B. A. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet. 1993 Aug;53(2):305–313. [PMC free article] [PubMed] [Google Scholar]
  5. Huson S. M., Compston D. A., Clark P., Harper P. S. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet. 1989 Nov;26(11):704–711. doi: 10.1136/jmg.26.11.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Huson S. M., Compston D. A., Harper P. S. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. II. Guidelines for genetic counselling. J Med Genet. 1989 Nov;26(11):712–721. doi: 10.1136/jmg.26.11.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Korf B. R. Diagnostic outcome in children with multiple café au lait spots. Pediatrics. 1992 Dec;90(6):924–927. [PubMed] [Google Scholar]
  8. Lázaro C., Ravella A., Gaona A., Volpini V., Estivill X. Neurofibromatosis type 1 due to germ-line mosaicism in a clinically normal father. N Engl J Med. 1994 Nov 24;331(21):1403–1407. doi: 10.1056/NEJM199411243312102. [DOI] [PubMed] [Google Scholar]
  9. Obringer A. C., Meadows A. T., Zackai E. H. The diagnosis of neurofibromatosis-1 in the child under the age of 6 years. Am J Dis Child. 1989 Jun;143(6):717–719. doi: 10.1001/archpedi.1989.02150180099028. [DOI] [PubMed] [Google Scholar]
  10. Riccardi V. M., Lewis R. A. Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants. Am J Hum Genet. 1988 Feb;42(2):284–289. [PMC free article] [PubMed] [Google Scholar]
  11. Upadhyaya M., Shaw D. J., Harper P. S. Molecular basis of neurofibromatosis type 1 (NF1): mutation analysis and polymorphisms in the NF1 gene. Hum Mutat. 1994;4(2):83–101. doi: 10.1002/humu.1380040202. [DOI] [PubMed] [Google Scholar]
  12. Viskochil D., Buchberg A. M., Xu G., Cawthon R. M., Stevens J., Wolff R. K., Culver M., Carey J. C., Copeland N. G., Jenkins N. A. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell. 1990 Jul 13;62(1):187–192. doi: 10.1016/0092-8674(90)90252-a. [DOI] [PubMed] [Google Scholar]
  13. Wallace M. R., Marchuk D. A., Andersen L. B., Letcher R., Odeh H. M., Saulino A. M., Fountain J. W., Brereton A., Nicholson J., Mitchell A. L. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990 Jul 13;249(4965):181–186. doi: 10.1126/science.2134734. [DOI] [PubMed] [Google Scholar]
  14. Wu B. L., Boles R. G., Yaari H., Weremowicz S., Schneider G. H., Korf B. R. Somatic mosaicism for deletion of the entire NF1 gene identified by FISH. Hum Genet. 1997 Feb;99(2):209–213. doi: 10.1007/s004390050341. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES