Neurological Sciences

, Volume 39, Issue 9, pp 1631–1633 | Cite as

Refractory epilepsy in Norrie disease

  • Gonçalo CaçãoEmail author
  • Cristina Garrido
  • Vasco Miranda
  • Jorge Pinto-Basto
  • João Chaves
  • Rui Chorão
Letter to the Editor

Dear Professor Federico,

Norrie disease is a NDP-related retinopathy characterized by congenital blindness with progressive loss of hearing and neurological features first reported by Gordon Norrie in 1927 [1]. Its gene mutation has been recently described and helped to define a large spectrum of phenotypic manifestations. The diagnosis relies on a combination of clinical findings and molecular genetic testing, which identifies pathogenic variants in approximately 95% of affected males [1, 2, 3]. Norrie disease is an X-linked recessive disorder resulting from a disruption of the NDP gene (Xp11.4) [2], which encodes the protein norrin. This is a secreted protein with a cysteine-knot motif that acts as a ligand in the WNT receptor-b-catenin signal transduction pathway, which is thought to regulate retinal angiogenesis and to be required for regression of hyaloid vessels in the eye [2]. In the inner ear, it is thought to regulate vascular maintenance since hearing is normal in early...


Compliance with ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Sims KB. NDP-related retinopathies. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews® [internet]. Seattle (WA): University of Washington, Seattle; 1993–2017. 1999 Jul 30 [updated 2014 Sep 18]Google Scholar
  2. 2.
    Smith SE, Mullen TE, Graham D, Sims KB, Rehm HL (2012) Norrie disease: extraocular clinical manifestations in 56 patients. Am J Med Genet Part A 158A:1909–1917CrossRefPubMedGoogle Scholar
  3. 3.
    Okumura A, Arai E, Kitamura Y, Abe S, Ikeno M, Fujimaki T, Yamamoto T, Shimizu T (2015 Nov) Epilepsy phenotypes in siblings with Norrie disease. Brain and Development 37(10):978–982CrossRefPubMedGoogle Scholar
  4. 4.
    Lev D, Weigl Y, Hasan M, Gak E, Davidovich M, Vinkler C, Leshinsky-Silver E, Lerman-Sagie T, Watemberg N (2007) A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms. Am J Med Genet Part A 143A:921–924CrossRefPubMedGoogle Scholar
  5. 5.
    Yamada K, Limprasert P, Ratanasukon M, Tengtrisorn S, Yingchareonpukdee J, Vasiknanonte P, Kitaoka T, Ghadami M, Niikawa N, Kishino T (2001) Two Thai families with Norrie disease (ND): association of two novel missense mutations with severe ND phenotype, seizures, and a manifesting carrier. Am J Med Genet 100:52–55CrossRefPubMedGoogle Scholar
  6. 6.
    Donnai D, Mountford RC, Read AP (1988) Norrie disease resulting from a gene deletion: clinical features and DNA studies. J Med Genet 25:73–78CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Suarez-Merino B, Bye J, McDowall J, Ross M, Craig IW (2001) Sequence analysis and transcript identification within 1.5MB of DNA deleted together with the NDP and MAO genes in atypical Norrie disease patients presenting with a profound phenotype. Hum Mutat 17:523CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Neurology Department, Hospital de Santo AntónioCentro Hospitalar do PortoPortoPortugal
  2. 2.Pediatrics Department, Centro Materno Infantil do NorteCentro Hospitalar do PortoPortoPortugal
  3. 3.Ophtalmology Department, Hospital de Santo AntónioCentro Hospitalar do PortoPortoPortugal
  4. 4.CGC GeneticsPortoPortugal
  5. 5.Neurophisiology Departement, Hospital de Santo AntónioCentro Hospitalar do PortoPortoPortugal

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