Leber’s Congenital Amaurosis

Clinical Heterogeneity and Electroretinography in 27 Patients
  • Matthias C. Grieshaber
  • Eugen Boltshauser
  • Günter Niemeyer


Purpose: Clinical evaluation of 42 patients with primarily suspected diagnosis of Leber's congenital amaurosis (LCA).

Methods: We used the electroretinogram (ERG), visual acuity, fundus ap- pearance, age of onset, and systemic findings to confirm or revise the diagnosis of LCA.

Results: Twenty-four patients had a non-recordable ERG, and 3 showed small, residual, mainly cone-driven b-waves. Profound visual loss ranged from no light perception to 20/200. Visual acuity of light perception was frequent at <1 year of age. Three patients never had light perception. Most patients had a stable visual acuity despite progressive retinal pigmentary changes. A normal fundus was seen predominantly in patients younger than 1 year of age, but could also be found in patients of all age groups. The first, and frequently the only pigmentary changes were vascular attenuation and rarefaction, later in life heterogeneous retinal findings appeared. None of the 9 reexamined patients showed a normal fundus. Nystagmus and strabismus were principal presenting symptoms. Eleven patients presented with the oculodigital sign, three of them were enophthalmic, and 12 patients showed roving eye movements. Patients with additional (nonocular) findings such as mental retardation (n = 12), renal (n = 3) and skeletal (n = 4) abnormalities revealed no different ERG- or ophthalmoscopic findings than the remaining patients. Twelve patients revealed abnormal psychomotor development.

From the initial cohort of 42 patients with suspected LCA, the diagnosis had to be revised in 15 cases as follows: juvenile RP (n = 8), infantile Refsum syndrome (n = 1), and 6 patients could not yet be classified with certainty.

Conclusion: Bilateral visual impairment in infants should be assessed clinically and electroretinographically within the first year. Later in life, the diagnosis of LCA can be a challenge due to its phenotypical heterogeneity. Systemic disorders are inde pendent of ocular findings. In patients older than two years with non-recordable ERG, visual acuity better than 201200, progressive visual loss, normal pupillary responses, absent oculodigital sign and absence of systemic abnormalities, juvenile retinitis pigmentosa should be considered.


Visual Acuity Retinal Pigment Epithelium Retinitis Pigmentosa Retinal Vessel Light Perception 
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  1. 1.
    T. Leber, 1869, Ueber Retinitis pigmentosa und angeborene Amaurose, Graefes Arch. Clin. Exp. Ophthalmol. 15:1–25.Google Scholar
  2. 2.
    C.H. Alström and O.A. Olson, 1957, Heredo-retinopathia congenitalis. Monohybrida recessiva autosomalis, Hereditas 43:1–77.Google Scholar
  3. 3.
    S.R. Lambert, S. Sherman, D. Taylor, A. Kriss, R. Coffey, and M. Pembrey, 1993, Concordance and recessive inheritance of Leber congenital amaurosis, Am. J. Med. Genet. 46:275–277.PubMedCrossRefGoogle Scholar
  4. 4.
    P. Gouras, 1970, Electroretinography: Some basic principles. Investig. Ophthalmol. 9:557–569.Google Scholar
  5. 5.
    G. Niemeyer, 1998, Electroretinography: An useful tool to assess retinal function in clinical neurophysiology. In: 9th european congress of clinical neurophysiology, edited by DeWeerd Stalberg E.V. and Zidar J. Al W., Ljubljana Slovenia: Monduzzi Editore, pp. 201–208.Google Scholar
  6. 6.
    G. Niemeyer, B. Grbovic, and B. Gloor, 1993, Elektroretinographie-Diagnostik beim Kleinkind. Electroretinographic diagnosis in infants, Klin. Monatsbl. Augenheilkd. 202:417–421.PubMedGoogle Scholar
  7. 7.
    G. Niemeyer, 1999, Vom Symptom zur Elektroretinographie-Diagnose (From symptom to ERG-diagnoses), Klin. Monatsbl. Augenheilkd. (in press).Google Scholar
  8. 8.
    A. Kriss and I. Russell-Eggitt, 1992, Electrophysiological assessment of visual pathway function in infants, Eye 6:145–153.PubMedGoogle Scholar
  9. 9.
    R.J.A. Wanders, E. Boltshauser, B. Steinmann, M.A. Spycher, R.B.H. Schutgens, H. van den Bosch, and J.M. Tager, 1990, Infantile phytanic acid storage disease, a disorder of peroxisome biogenesis: a case report, J. Neurol. Sci. 98:1–11.PubMedCrossRefGoogle Scholar
  10. 10.
    G. Niemeyer and P. Stähli, 1996, ERG-Diagnose und Differentialdiagnose: Untersuchungsergebnisse über 6 Jahre. Electroretinographic diagnoses and differential diagnoses: Results over 6 years, Klin. Monatsbl. Augenheilkd. 208:306–310.CrossRefGoogle Scholar
  11. 11.
    S.G. Foxman, J.R. Heckenlively, J.B. Bateman, and J.D. Wirtschafter, 1985, Classification of congenital and early onset retinitis pigmentosa, Arch. Ophthalmol. 103:1502–1506.PubMedGoogle Scholar
  12. 12.
    J. Kaplan, D. Bonneau, J. Frézal, A. Munnich, and J.L. Dufier, 1990, Clinical and genetic heterogeneity in retinitis pigmentosa, Hum. Genet. 85:635–642.PubMedCrossRefGoogle Scholar
  13. 13.
    M. Steinlin, M. Schmid, K. Landau, and E. Boltshauser, 1997, Followup in children with Joubert syndrome, Neuropediatrics 28:204–211.PubMedCrossRefGoogle Scholar
  14. 14.
    B. Kendall, D. Kingsley, S.R. Lambert, D. Taylor, and P. Finn, 1990, Joubert syndrome: a clinico-radiological study, Neuroradiology 31:502–506.PubMedCrossRefGoogle Scholar
  15. 15.
    S.R. Lambert, A. Kriss, D. Taylor, R. Coffey, and B. Soc, M. Pembrey, 1989, Leber’s congenital amaurosis: A followup and diagnostic reappraisal of 75 patients, Am. J. Ophthalmol. 107:624–631.PubMedGoogle Scholar
  16. 16.
    K. Mizuno, Y. Takei, M.L. Sears, W.S. Peterson, R.E. Carr, and L.M. Jampol, 1977, Leber’s congenital amaurosis, Am. J. Ophthalmol. 83:34–42.Google Scholar
  17. 17.
    A.B. Fulton and R.M. Hansen, 1985, Electroretinography: Application to clinical studies of infants, J. Pediat. Ophthalmol. & Strabismus 22:251–255.Google Scholar
  18. 18.
    I. Casteels, W. Spileers, Ph. Demaerel, P. Casaer, P. De Cock, L. Dralands, and L. Missotten, 1996, Leber congenital amaurosis—differential diagnosis, ophthalmological, and neuroradiological report of 18 patients, Neuropediatrics 27:189–193.PubMedCrossRefGoogle Scholar
  19. 19.
    G. Niemeyer, 1989, Indikationen zu elektrophysiologischen Untersuchungen des Auges, Klin. Monatsbl. Augenheilkd. 194:333–336.PubMedGoogle Scholar
  20. 20.
    R. Schroeder, M.B. Mets, and I.H. Maumenee, 1987, Leber’s congenital amaurosis. Retrospective review of 43 cases and a new fundus finding in two cases, Arch. Ophthalmol. 105:356–359.PubMedGoogle Scholar
  21. 21.
    K.L. Heher, E.L. Traboulski, and I.H. Maumenee, 1992, The natural history of Leber’s congenital amaurosis, age-related findings in 35 patients, Ophthalmology 99:241–245.Google Scholar
  22. 22.
    R.S. Wagner, A.R. Caputo, L. Nelson, and D. Zanoni, 1985, High hyperopia in Leber’s congenital amaurosis, Arch. Ophthalmol. 103:1507–1509.Google Scholar
  23. 23.
    M.C. Grieshaber, and G. Niemeyer, 1998, Kongenitale Amaurose Leber: Diagnose, Verlauf und Differentialdiagnose. Leber’s congenital amaurosis: Diagnosis, course, and differential diagnosis, Klin. Monatsbl. Augenheilkd. 212:309–310.PubMedGoogle Scholar
  24. 24.
    A. Camuzat, H. Dollfuss, J.M. Rozet, S. Gerber, D. Bonneau, M. Bonnemaison, M.C. Briard, J.-L. Dufier, I. Ghazi, C. Leowski, J. Weissenbach, J. Frézal, A. Munnich, and J. Kaplan, 1995, A gene for Leber’s congenital amaurosis maps to chromosome 17p, Hum. Mol. Genet. 4:1447–1452.PubMedCrossRefGoogle Scholar
  25. 25.
    I. Perrault, J.M. Rozet, P. Calvas, S. Gerber, A. Camuzat, H. Dollfus, S. Châtelin, E. Souied, I. Ghazi, C. Leowski, M. Bonnemaison, D. LePaslier, J. Frézal, J.-L. Dufier, S. Pittler, A. Munnich, and J. Kaplan, 1996, Retinal-specific guanylate cyclase gene mutations in Leber’s congenital amaurosis, Nature genetics 14:461–464.PubMedCrossRefGoogle Scholar
  26. 26.
    I. Perrault, J.M. Rozet, A.L. Delezoide, S. Gerber, E. Souied, A. Cabot, A. Munnich, and J. Kaplan, 1998, Histological study and in situ hybridization of the retGC gene in a human fetus affected with Leber’s congenital amaurosis (LCA1), Invest. Ophthalmol. Vis. Sci. 39:1042.Google Scholar
  27. 27.
    S. Dharmaraj, J.M. Robitaille, D. Zhu, Y.Y. Li, and I.H. Maumenee, 1998, An additional locus for Leber’s congenital amaurosis maps to chromosome 6, Invest. Ophthalmol. Vis. Sci. 39:296.Google Scholar
  28. 28.
    A. Nicoletti, D.J. Wong, K. Kawase, L.H. Gibson, T.L. Yang-Feng, J.E. Richards, and D.A. Thompson, 1995, Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium, Hum. Mol. Gen. 4:641–649.PubMedCrossRefGoogle Scholar
  29. 29.
    C.-O. Bavik, U Eriksson, R.A. Allen, and P.A. Peterson, 1991, Identification and partial characterization of a retinal pigment epithelial membrane receptor for plasma retinol-binding protein, J. Biol. Chem. 266:14978–14985.PubMedGoogle Scholar
  30. 30.
    C.-O. Bavik, C. Busch, and U. Eriksson, 1992, Characterization of a plasma retinol-binding protein membrane receptor expressed in the retinal pigment epithelium, J. Biol. Chem. 267:23035–23042.PubMedGoogle Scholar
  31. 31.
    A. Simon, U. Hellman, C. Wenstedt, and U. Eriksson, 1995, The retinal pigment epithelial-specificl 1-cis retinal dehydrogenase belongs to the family of short chain alcohol dehydrogenases, J. Biol. Chem. 270:1107–1112.PubMedCrossRefGoogle Scholar
  32. 32.
    S. Gu, D.A. Thompson, C.R. Srisailapathy Srikumari, B. Lorenz, U. Finckh, A. Nicoletti, K.R. Murthy, M. Rathmann, G. Kumaramanickavel, M.J. Denton, and A. Gal, 1997, Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy, Nature Genetics 17:194–197.PubMedCrossRefGoogle Scholar
  33. 33.
    E. Apfelstedt-Sylla, S. Gu, A. Gal, and E. Zrenner, 1998, Clinical findings in patients with retinal dystrophies caused by mutations in RPE65, Invest. Ophthalmol. Vis. Sci. 39:967.Google Scholar
  34. 34.
    H. Morimura, G.A. Fishman, S.A. Grover, A.B. Fulton, E.L. Berson, and T.P. Dryja, 1998, Mutations in the RPE65 gene in patients with recessive retinitis pigmentosa or Leber’s congenital amaurosis, Invest. Ophthalmol. Vis. Sci. 39:293.Google Scholar
  35. 35.
    J.M. Rozet, I. Perrault, I. Ghazi, S. Gerber, E. Souied, A. Cabot, J.L. Dufier, A. Munnich, and J. Kaplan, 1998, Exclusion of the RPE65 gene in 26 families affected with Leber’s congenital amaurosis (LCA), Invest. Ophthalmol. Vis. Sci. 39:297.Google Scholar
  36. 36.
    S.R. Lambert, D. Taylor, and A. Kriss, 1989, The infant with nystagmus, normal appearing fundi, but an abnormal ERG, Survey of Ophthalmol. 34:173–186.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  • Matthias C. Grieshaber
    • 1
  • Eugen Boltshauser
    • 2
  • Günter Niemeyer
    • 1
  1. 1.Clinical ERG-LaboratorDepartment of OphthalmologySwitzerland
  2. 2.University Children’s HospitalZürichSwitzerland

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