Familial Cancer

, Volume 11, Issue 4, pp 653–656

Parent-of-origin in individuals with familial neurofibromatosis type 1 and optic pathway gliomas

  • K. J. Johnson
  • M. J. Fisher
  • R. L. Listernick
  • K. N. North
  • E. K. Schorry
  • D. Viskochil
  • M. Weinstein
  • J. B. Rubin
  • D. H. Gutmann
Short Communication


Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant cancer syndromes worldwide. Individuals with NF1 have a wide variety of clinical features including a strongly increased risk for pediatric brain tumors. The etiology of pediatric brain tumor development in NF1 is largely unknown. Recent studies have highlighted the contribution of parent-of-origin effects to tumorigenesis in sporadic cancers and cancer predisposition syndromes; however, there is limited data on this effect for cancers arising in NF1. To increase our understanding of brain tumor development in NF1, we conducted a multi-center retrospective chart review of 240 individuals with familial NF1 who were diagnosed with a pediatric brain tumor (optic pathway glioma; OPG) to determine whether a parent-of-origin effect exists overall or by the patient’s sex. Overall, 50 % of individuals with familial NF1 and an OPG inherited the NF1 gene from their mother. Similarly, by sex, both males and females were as likely to inherit the NF1 gene from their mother as from their father, with 52 % and 48 % of females and males with OPGs inheriting the NF1 gene from their mother. In conclusion, in contrast to findings from other studies of sporadic cancers and cancer predisposition syndromes, our results indicate no parent-of-origin effect overall or by patient sex for OPGs in NF1.


Parent-of-origin Neurofibromatosis type 1 Optic pathway glioma Brain tumor 


  1. 1.
    Lynch TM, Gutmann DH (2002) Neurofibromatosis 1. Neurol Clin 20(3):841–865PubMedCrossRefGoogle Scholar
  2. 2.
    Littler M, Morton NE (1990) Segregation analysis of peripheral neurofibromatosis (NF1). J Med Genet 27(5):307–310PubMedCrossRefGoogle Scholar
  3. 3.
    Dalla Via P, Opocher E, Pinello ML et al (2007) Visual outcome of a cohort of children with neurofibromatosis type 1 and optic pathway glioma followed by a pediatric neuro-oncology program. Neuro Oncol 9(4):430–437PubMedCrossRefGoogle Scholar
  4. 4.
    Josefson J, Listernick R, Fangusaro JR, Charrow J, Habiby R (2011) Growth hormone excess in children with neurofibromatosis type 1-associated and sporadic optic pathway tumors. J Pediatr 158(3):433–436PubMedCrossRefGoogle Scholar
  5. 5.
    van Vliet CM, Dowty JG, van Vliet JL et al (2011) Dependence of colorectal cancer risk on the parent-of-origin of mutations in DNA mismatch repair genes. Hum Mutat 32(2):207–212PubMedCrossRefGoogle Scholar
  6. 6.
    Kong A, Steinthorsdottir V, Masson G et al (2009) Parental origin of sequence variants associated with complex diseases. Nature 462(7275):868–874PubMedCrossRefGoogle Scholar
  7. 7.
    Yeap PM, Tobias ES, Mavraki E et al (2011) Molecular analysis of pheochromocytoma after maternal transmission of SDHD mutation elucidates mechanism of parent-of-origin effect. J Clin Endocrinol Metab 96(12):E2009–E2013PubMedCrossRefGoogle Scholar
  8. 8.
    Muller U (2011) Pathological mechanisms and parent-of-origin effects in hereditary paraganglioma/pheochromocytoma (PGL/PCC). Neurogenetics 12(3):175–181PubMedCrossRefGoogle Scholar
  9. 9.
    Lewis RA, Gerson LP, Axelson KA, Riccardi VM, Whitford RP (1984) von Recklinghausen neurofibromatosis. II. Incidence of optic gliomata. Ophthalmology 91(8):929–935PubMedGoogle Scholar
  10. 10.
    Miller M, Hall JG (1978) Possible maternal effect on severity of neurofibromatosis. Lancet 2(8099):1071–1073PubMedCrossRefGoogle Scholar
  11. 11.
    Riccardi VM, Wald JS (1987) Discounting an adverse maternal effect on severity of neurofibromatosis. Pediatrics 79(3):386–393PubMedGoogle Scholar
  12. 12.
    Szudek J, Joe H, Friedman JM (2002) Analysis of intrafamilial phenotypic variation in neurofibromatosis 1 (NF1). Genet Epidemiol 23(2):150–164PubMedCrossRefGoogle Scholar
  13. 13.
    Reilly KM, Tuskan RG, Christy E et al (2004) Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc Natl Acad Sci USA 101(35):13008–13013PubMedCrossRefGoogle Scholar
  14. 14.
    Tuskan RG, Tsang S, Sun Z et al (2008) Real-time PCR analysis of candidate imprinted genes on mouse chromosome 11 shows balanced expression from the maternal and paternal chromosomes and strain-specific variation in expression levels. Epigenetics 3(1):43–50PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • K. J. Johnson
    • 1
    • 2
    • 12
  • M. J. Fisher
    • 3
    • 4
  • R. L. Listernick
    • 5
  • K. N. North
    • 6
  • E. K. Schorry
    • 7
  • D. Viskochil
    • 8
  • M. Weinstein
    • 9
  • J. B. Rubin
    • 10
  • D. H. Gutmann
    • 11
  1. 1.Brown SchoolWashington University in St. LouisSt. LouisUSA
  2. 2.Department of Pediatrics, School of MedicineWashington University in St. LouisSt. LouisUSA
  3. 3.Department of Oncology, The Children’s Hospital of PhiladelphiaUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Pediatrics, The Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Children’s Memorial HospitalChicagoUSA
  6. 6.University of SydneySydneyAustralia
  7. 7.Cincinnati Children’s HospitalCincinnatiUSA
  8. 8.University of UtahSalt Lake CityUSA
  9. 9.Sick KidsUniversity of TorontoTorontoCanada
  10. 10.Division of Pediatric Hematology-Oncology, Department of PediatricsWashington University School of MedicineSt. LouisUSA
  11. 11.Department of NeurologyWashington University School of MedicineSt. LouisUSA
  12. 12.Public Health Program, George Warren Brown School, 237 Goldfarb Hall, Campus Box 1196Washington University in St. LouisSt. LouisUSA

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