Familial Dysautonomia in Review: Diagnosis and Treatment of Ocular Manifestations

  • Cathleen A. Josaitis
  • Martin Matisoff
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 506)


Familial dysautonomia (FD) is a rare genetic disease belonging to a group of disorders known as hereditary sensory and autonomic neuropathies. Incomplete sensory and autonomic neuron development results in general sensory dysfunction and variable autonomic dysfunction. Currently, only about 50% of FD patients reach 30 years of age.1 With rare exception, FD, also known as HSAN (or HSN) type III and Riley-Day syndrome, affects patients of Ashkenazi Jewish descent and is included among the Jewish genetic diseases (e.g., Gaucher disease, Tay-Sachs disease).


Experimental Autoimmune Encephalomyelitis Acinar Cell Lacrimal Gland Human Embryonal Kidney Cell Line Tumor Necrosis Factor Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    The National Foundation for Jewish Genetic Diseases, Inc. Available at: Accessed August 10, 2000.
  2. 2.
    F. Payne, Neuro-ophthalmology, Arch Ophthalmol. 50:664 (1953).CrossRefGoogle Scholar
  3. 3.
    A.E. Braley, The lids, lacrimal apparatus and conjunctiva, Arch Ophthalmol. 51:91 (1954).CrossRefGoogle Scholar
  4. 4.
    J.H. Dunnington, Congenital alacrima in familial autonomic dysfunction, Arch Ophthalmol. 52:925 (1954).CrossRefGoogle Scholar
  5. 5.
    S.D. Liebman, Ocular manifestations of Riley-Day syndrome—familial autonomic dysfunction, Arch Ophthalmol. 56:119 (1956a).CrossRefGoogle Scholar
  6. 6.
    S.D. Liebman, Riley-Day syndrome (familial dysautonomia), an ocular survey of nineteen cases, Arch Ophthalmol. 58:188(1957).CrossRefGoogle Scholar
  7. 7.
    J. Francois, The Riley-Day syndrome: familial dysautonomia, central autonomic dysfunction, Ophthalmologica 174:20(1977).CrossRefPubMedGoogle Scholar
  8. 8.
    F. Murillo-Lopez and S.C. Pflugfelder, Dry eye, in: The Cornea, J. Krachmer and M. Mannis, eds., Mosby, St Louis (1996).Google Scholar
  9. 9.
    I.G. Kroop, The production of tears in familial dysautonomia: preliminary report, J Pediatr. 48:328 (1956).CrossRefPubMedGoogle Scholar
  10. 10.
    A.A. Smith, J. Dancis, and G. Breinin, Ocular responses to autonomic drugs in familial dysautonomia, Invest Ophthalmol Vis Sci. 4:358 (1965).Google Scholar
  11. 11.
    S.D. Liebman, Ocular manifestations of Riley-Day syndrome, Arch Ophthalmol. 56:719 (1956b).CrossRefGoogle Scholar
  12. 12.
    M.F. Goldberg, J.W. Payne, and P.W. Brunt, Ophthalmologic studies of familial dysautonomia, Arch Ophthalmol. 80:732 (1968).CrossRefPubMedGoogle Scholar
  13. 13.
    F.B. Axelrod, R. Nachtigal, and J. Dancis, Familial dysautonomia: diagnosis, pathogenesis and management, Adv Pediatr. 21:75 (1974).PubMedGoogle Scholar
  14. 14.
    S.D. Liebman, Riley-Day syndrome: long-term ophthalmic observations, Trans Am Ophthalmol Soc. 66:95 (1968).CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    J.F. Rizzo III, S. Lessell, and S.D. Liebman, Optic atrophy in familial dysautonomia, Am J Ophthalmol 102:463 (1986).CrossRefPubMedGoogle Scholar
  16. 16.
    M. Groom, M.D. Kay, and G.F. Corrent, Optic neuropathy in familial dysautonomia, J Neuroophthalmol. 17:101 (1997).CrossRefPubMedGoogle Scholar
  17. 17.
    C.G. Keith, Riley-Day syndrome, Br J Ophthalmol. 49:667 (1965).CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    S. Braun-Vallon and N. Bessman, La dysautonomie familiale à propos de 3 observations, Ann Oculist. 193:561 (1960).Google Scholar
  19. 19.
    I.S. Pilger, Familial dysautonomia: report of case with stimulation of tear production by prostigmine, Am J Ophthalmol. 43:285 (1957).CrossRefPubMedGoogle Scholar
  20. 20.
    Y. Filler, A.A. Smith, S. Stone, and J. Dancis, Respiratory control in familial dysautonomia, J Pediatr. 66:509(1965).CrossRefPubMedGoogle Scholar
  21. 21.
    J.C. Brown and R.J. Johns, Nerve conduction in familial dysautonomia (Riley-Day syndrome), JAMA. 201:118(1967).CrossRefGoogle Scholar
  22. 22.
    A.A. Smith and J. Dancis, Catecholamine release in familial dysautonomia, New Engl J Med. 277:61 (1967).CrossRefPubMedGoogle Scholar
  23. 23.
    R.K. Winkelmann, A. Bourland, and A.A. Smith, Nerves in the skin of a patient with familial dysautonomia (Riley-Day syndrome), Pediatrics. 38:1060 (1966).PubMedGoogle Scholar
  24. 24.
    Online Mendelian Inheritance in Man, OMIM ™. Johns Hopkins University, Baltimore, MD. MIM Number 223900. Last edited 4/12/99. Available at Accessed July 27, 2000.
  25. 25.
    A.J. Aguayo, C.P. Nair, and G.M. Bray, Peripheral nerve abnormalities in the Riley-Day syndrome. Findings in a sural nerve biopsy, Arch Neurol. 24:106 (1971).CrossRefPubMedGoogle Scholar
  26. 26.
    S.L. Anderson, R. Coli, I.W. Daly, E.A. Kichula, M.J. Rork, S.A. Volpi, J. Ekstein, and B.Y. Rubin, Familial dysautonomia is caused by mutations of the IKAP gene, Am J Human Genet. 68:753 (2001).CrossRefGoogle Scholar
  27. 27.
    A. Blumenfeld, S.A. Slaugenhaupt, C.B. Liebert, V. Temper, C. Maayan, S. Gill, et al. Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31, Am J Hum Genet. 64:1110 (1999).CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    J.F. Gusella, Massachusetts General Hospital. National Institute of Neurological Disorders and Stroke (NINDS). Grant No. 5R01NS36326–02 (1997).Google Scholar
  29. 29.
    A. Blumenfeld, S.A. Slaugenhaupt, F.B. Axelrod, D.E. Lucente, C. Maayan, C.B. Liebert, et al. Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis, Nat Genet. 4:160 (1993).CrossRefPubMedGoogle Scholar
  30. 30.
    A. Blumenfeld, F.B. Axelrod, V. Tamper, and C. Maayan, Localization of the familial dysautonomia gene to chromosome 9q31–33 and the development of a genetic test for the disease, Harefuah. 128:97 (1995).PubMedGoogle Scholar
  31. 31.
    New York University Medical Center. Available at: Accessed July 27, 2000.
  32. 32.
    CM. Eng, S.A. Slaugenhaupt, A. Blumenfeld, F.B. Axelrod, J.F. Gusella, and R.J. Desnick, Prenatal diagnosis of familial dysautonomia by analysis of linked CA-repeat polymorphisms on chromosome 9q31–9q33, Am J Med Genet. 59:349 (1995).CrossRefPubMedGoogle Scholar
  33. 33.
    New York University Medical Center. Available at: Accessed June 5, 2001.
  34. 34.
    C.M. Riley, R.L. Day, D.M. Greeley, and W.S. Langford, Central autonomic dysfunction with defective lacrimation, Pediatrics. 3:468 (1949).PubMedGoogle Scholar
  35. 35.
    National Organization for Rare Disorders, 2000.Google Scholar
  36. 36.
    F.B. Axelrod, K. Iyer, I. Fish, J. Pearson, M.E. Sein, and N. Spielholz, Progressive sensory loss in familial dysautonomia, Pediatrics. 67:517 (1981).PubMedGoogle Scholar
  37. 37.
    J. Pearson, G. Gallo, M. Gluck, and F.B. Axelrod, Renal disease in familial dysautonomia. Kidney Int. 17:102(1980).CrossRefPubMedGoogle Scholar
  38. 38.
    F.B. Axelrod, Familial dysautonomia: a 47-year perspective. How technology confirms clinical acumen, J Pediatr. 132:S2 (1998).CrossRefGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 2002

Authors and Affiliations

  • Cathleen A. Josaitis
    • 1
  • Martin Matisoff
    • 1
  1. 1.Allergan, Inc.IrvineUSA

Personalised recommendations