Skip to main content
SpringerLink
Log in

X-Linked Idiopathic Infantile Nystagmus (XLIIN): Case Report and Review of Literature

  • Pediatric Ophthalmology (S Robbins, Section Editor)
  • Published:
Current Ophthalmology Reports Aims and scope Submit manuscript

Abstract

ᅟ

Infantile nystagmus syndrome (INS) is one of the most common forms of nystagmus. It can occur in isolation or with other ocular anomalies. While nystagmus is usually sporadic, familial cases exist and are most commonly X-linked with incomplete penetrance and variable expressivity. There are over 45 mutations reported in the FRMD7 gene.

Purpose of Review

This review describes the possible underlying mechanisms of infantile nystagmus syndrome, clinical characterization, and principles of management including behavioral, refractive, pharmacological, and surgical options as well as determines the genetic basis of INS in one large Caucasian family with a novel mutation in FRMD7.

Recent Findings

Newer generation optical coherence tomography (OCT) allows for accurate phenotypical characterization of genetic subtypes of INS.

Summary

Further studies into identifying unknown genetic mutations involved in infantile nystagmus syndrome will allow for development of cellular and animal models to help classify INS and guide future therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dell’Osso LF. Congenital, latent and manifest latent nystagmus—similarities, differences and relation to strabismus. Jap J Ophthalmol. 1985;29:351–68.

    Google Scholar 

  2. Sarvananthan N, Surendran M, Roberts E, et al. The prevalence of nystagmus: the leicestershire nystagmus survey. Investig Ophthalmol Vis Sci. 2009;50(11):5201–6.

    Article  Google Scholar 

  3. Kerrison JB, Vagefi MR, Barmada MM, et al. Congenital motor nystagmus linked to Xq26-q27. Am J Hum Genet. 1999a;64:600–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cabot A, et al. A gene for X-linked idiopathic congenital nystagmus (NYS1) maps to chromosome Xp11.4–p11.3. Am J Hum Genet. 1999;64:1141–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bassi MT, et al. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet. 1995;10:13–9.

    Article  CAS  PubMed  Google Scholar 

  6. Kerrison JB, et al. Congenital motor nystagmus linked to Xq26–q27. Am J Hum Genet. 1999b;64:600–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tarpey PS, Stevens C, Teague J, et al. Mutations in the gene encoding the sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation. Am J Hum Genet. 2006;79:1119–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. He X, Gu F, Wang Y, Yan J, Zhang M, Huang S, Ma X. A novel mutation in FRMD7 causing X-linked idiopathic congenital nystagmus in a large family. Mol Vis. 2008;14:56–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhang B, Liu Z, Zhao G, et al. Novel mutations of the FRMD7 gene in X-linked congenital motor nystagmus. Mol Vis. 2007;13:1674–9.

    CAS  PubMed  Google Scholar 

  10. Fingert J, Roos B, Eyestone M, Pham J, Mellot M, Stone E. Novel intragenic FRMD7 deletion in a pedigree with congenital X-linked nystagmus. Ophthalmic Genet. 2010;31:77–80.

    Article  CAS  PubMed  Google Scholar 

  11. • Watkins R, Thomas M, Talbot C, Gottlob I, Shackleton S. The role of FRMD7 in idiopathic infantile nystagmus. J Ophthalmol. 2012;2012:460956. FRMD7 expression analysis involved in axogenesis, dendritogenesis, and neuronal guidance in the areas of the brain which control eye movements

    PubMed  Google Scholar 

  12. Zhang X, Xianglian G, Yu Y, et al. Identification of three novel mutations in the FRMD7 Gene for X-linked idiopathic congenital nystagmus. Sci Rep. 2014;4:3745.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Thomas N, Harris C, Hodgkins P. Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus. Ophthalmic Molecular Genetics. 2007;125(9):1255–63.

    Google Scholar 

  14. Liu Z, Mao S, Pu J, Ding Y, Zhang B, Ding M. A novel missense mutation in the FERM domain containing 7 (FRMD7) gene causing X-linked idiopathic congenital nystagmus in a Chinese family. Mol Vis. 2013;19:1834–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hu Y, Shen J, Zhang S, Yang T, Huang S, Yuan H. A novel splicing mutation of the FRMD7 gene in a Chinese family with X-linked congenital nystagmus. Mol Vis. 2012;18:87–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Schorderet D, Tiab L, Gaillard M, Lorenz B, Klainguti G, Kerrison J, Traboulsi E. Novel mutations in FRMD7 in X-linked congenital nystagmus. Hum Mutat. 2007;28:525.

    Article  PubMed  Google Scholar 

  17. •• Betts-Henderson J, Bartesaghi S, Crosier M, Lindsay S, Chen H, Salomoni P, Gottlob I, Nicotera P. The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development. Hum Molec Genet. 2010;19:342–51. Case study demonstrating FRMD7 protein co-localizes with CASK. First time demonstrating knockdown of FRMD7 could disrupt interaction with CASK during neuronal differentiation resulting in altered neurite development

    Article  CAS  PubMed  Google Scholar 

  18. •• Thomas M, Crosier M, Lindsay S, et al. The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain. 2011;134:892–902. Expression and phenotypic data suggest that congenital PAN arises from instability of the optokinetic-vestibular systems

    Article  PubMed  PubMed Central  Google Scholar 

  19. •• Watkins RJ, et al. A novel interaction between FRMD7 and CASK: evidence for a causal role in idiopathic infantile nystagmus. Hum Mol Genet. 2013;22:2105–18. Protein interaction of CASK recruiting FRMD7 to the plasma membrane promoting neurite outgrowth during development of the oculomotor neural network

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu JY, et al. Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation. J Hum Genet. 2007;52:565–70.

    Article  PubMed  Google Scholar 

  21. Dell’Osso LF, Daroff RB. Latent, manifest latent and congenital nystagmus. Arch Ophthalmol. 1979;97:1877–85.

    Article  PubMed  Google Scholar 

  22. Abadi RV, Dickinson CM, Pascal E, Whittle J, Worfolk R. Sensory and motor aspects of congenital nystagmus. In: Schmid R, Zambarbieri D, editors. Ocularmotor control and cognitive processes. Amsterdam: Elsevier; 1991. p. 249–62.

    Google Scholar 

  23. Dell’osso LF, Daroff RB. Congenital nystagmus waveforms and foveation strategy. Doc Ophthalmol. 1975;39(1):155–82.

    Article  PubMed  Google Scholar 

  24. Dell'Osso LF, et al. Eye movement recordings as a diagnostic tool in a case of congenital nystagmus. Am J Optom. 1972;49:3–13.

    Article  Google Scholar 

  25. Abadi RV, Bjerre A. Motor and sensory characteristics of infantile nystagmus. Br J Ophthalmol. 2002;86(10):1152–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Thomas S, Proudlock F, Sarvananthan N, et al. Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7. Brain. 2008;131:1259–67.

    Article  PubMed  Google Scholar 

  27. Hertle R, Dell’Osso L, Fitz Gibbon E, Yang D, Mellow S. Horizontal rectus muscle tenotomy in children with infantile nystagmus syndrome: a pilot study. J Aapos. 2004a;8:539–48.

    Article  PubMed  Google Scholar 

  28. Abadi RV, Carden D, Simpson J. A new treatment for congenital nystagmus. Br J Ophthalmol. 1980;64:2–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sharma P, Tandon R, Kumar S, Anand S. Reduction of congenital nystagmus amplitude with auditory biofeedback. J AAPOS. 2000;4(5):287–90.

    Article  CAS  PubMed  Google Scholar 

  30. Fresina M, Benedetti C, Marinelli F, Versura P, Campos EC. Astigmatism in patients with idiopathic congenital nystagmus. Graefes Arch Clin Exp Ophthalmol. 2013;251(6):1635–9.

    Article  PubMed  Google Scholar 

  31. Jayaramachandran P, Proudlock FA, Odedra N, Gottlob I, McLean RJ. A randomized controlled trial comparing soft contact lens and rigid gas-permeable lens wearing in infantile nystagmus. Ophthalmology. 2014;121(9):1827–36.

    Article  PubMed  Google Scholar 

  32. Dell'Osso LF, Traccis S, Erzurum SI. Contact lenses and congenital nystagmus. Clinical Vision Science. 1988;3:229–32.

    Google Scholar 

  33. Comer RM, Dawson EL, Lee JP. Baclofen for patients with congenital periodic alternating nystagmus. Strabismus. 2006;14(4):205–9.

    Article  CAS  PubMed  Google Scholar 

  34. Young YH, Huang TW. Role of clonazepam in the treatment of idiopathic downbeat nystagmus. Laryngoscope. 2001;111:1490–3.

    Article  CAS  PubMed  Google Scholar 

  35. • McLean R, Proudlock F, Thomas S, Degg C, Gottlob I. Congenital nystagmus: randomized, controlled, double-masked trial of memantine/gabapentin. Ann Neurol. 2007;61(2):130–8. Pharmacological agents such as memantine and gabapentin can improve visual acuity, reduce nystagmus intensity, and improve foveation in congenital nystagmus

    Article  CAS  PubMed  Google Scholar 

  36. Hertle RW, Yang D, Adkinson T, Reed M. Topical brinzolamide (Azopt) versus placebo in the treatment of infantile nystagmus syndrome (INS). Br J Ophthalmol. 2015;99(4):471–6.

    Article  PubMed  Google Scholar 

  37. Zhao JC, Chen T. Brinzolamide induced reversible corneal decompensation. Br J Ophthalmol. 2005;89:389–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Menon GJ, Vernon SA. Topical brinzolamide and metabolic acidosis. Br J Ophthalmol. 2006;90:247–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Carruthers J. The treatment of congenital nystagmus with Botox. J Pediatr Ophthalmol Strabismus. 1995;32:306–8.

    CAS  PubMed  Google Scholar 

  40. Tomsak RL, Remler BF, Averbuch-Heller L, Chandran M, Leigh RJ. Unsatisfactory treatment of acquired nystagmus with retrobulbar injection of botulinum toxin. Am J Ophthalmol. 1995;119:489–96.

    Article  CAS  PubMed  Google Scholar 

  41. Oleszczynska-Prost E. Botulinum toxin A in the treatment of congenital nystagmus in children. Klin Ocz. 2004;106:625–8.

    Google Scholar 

  42. Hertle RW, Dell’Osso LF. Clinical and ocular motor analysis of congenital nystagmus in infancy. J AAPOS. 1999;3(2):70–9.

    Article  CAS  PubMed  Google Scholar 

  43. Abadi RV, King-Smith PE. Congenital nystagmus modifies orientational detection. Vis Res. 1979;19:1409–11.

    Article  CAS  PubMed  Google Scholar 

  44. Felius J, Muhanna ZA. Visual deprivation and foveation characteristics both underlie visual acuity deficits in idiopathic infantile nystagmus. Invest Ophthalmol Vis Sci. 2013;54(5):3520–5.

    Article  PubMed  Google Scholar 

  45. Anderson JR. Causes and treatment of congenital eccentric nystagmus. Br J Ophthalmol. 1953;37:267–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Goto N. A study of optic nystagmus by the electrooculogram. Acta Soc Ophthalmol Jap. 1954;58:851–65.

    Google Scholar 

  47. Kestenbaum A. Une nouvelle opération du nystagmus. Bull Soc Ophtalmol Fr. 1953;6:599.

    CAS  PubMed  Google Scholar 

  48. Parks MM. Symposium: nystagmus. Congenital nystagmus surgery. Am Orthopt J. 1973;23:35–9.

    CAS  PubMed  Google Scholar 

  49. Calhoun JH, Harley RD. Surgery for abnormal head position in congenital nystagmus. Trans Am Ophthalmol Soc. 1973;71:70–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Kang NY, Isenberg SJ. Kestenbaum procedure with posterior fixation suture for anomalous head posture in infantile nystagmus. Graefes Arch Clin Exp Ophthalmol. 2009;247:981–7.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Graf M, Droutsas K, Kaufmann H. Congenital nystagmus: indication, results and dosage of Kestenbaum surgery in 34 patients. Klin Monatsbl Augenheilkd. 2000;217:334–9.

    Article  CAS  PubMed  Google Scholar 

  52. Lee IS, et al. Modified Kestenbaum surgery for correction of abnormal head posture in infantile nystagmus: outcome in 63 patients with graded augmentaton. Binocul Vis Strabismus Q. 2000;15:53–8.

    CAS  PubMed  Google Scholar 

  53. Chang YH, Chang JH, Han SH, Lee JB. Outcome study of two standard and graduated augmented modified Kestenbaum surgery protocols for abnormal head postures in infantile nystagmus. Binocul Vis Strabismus Q. 2007;22(4):235–41.

    PubMed  Google Scholar 

  54. Lee JB, Chin HS, Kim SS. The effect of Kestenbaum procedure for abnormal head position in infantile nystagmus. J Korean Ophthalmol Soc. 1995;36(10):1754–9.

    Google Scholar 

  55. Graf M, Droutsas K, Kaufmann H. Surgery for nystagmus related head turn: Kestenbaum procedure and artificial divergence. Graefes Arch Clin Exp Ophthalmol. 2001;239:334–41.

    Article  CAS  PubMed  Google Scholar 

  56. Seo HJ, Suh YW, Cho YA. Long-term outcome and recurrence of abnormal head posture after surgery in patients with nystagmus. J Korean Ophthalmol Soc. 2015;56(2):263–9.

    Article  Google Scholar 

  57. Hertle RW. Examination and refractive management of patients with nystagmus. Surv Ophthalmology. 2000;45:215–22.

    Article  CAS  Google Scholar 

  58. Hertle RW, Reese M. Clinical contrast sensitivity testing in patients with infantile nystagmus syndrome compared with age-matched controls. Am J Ophthalmol. 2007;143:1063–5.

    Article  PubMed  Google Scholar 

  59. Cüppers C. Problems in the surgery for ocular nystagmus. Klin Monatsbl Augenheilkd. 1971;159:145–7.

    PubMed  Google Scholar 

  60. Zubcov AA, Stark N, Weber A, Wizov SS, Reinecke RD. Improvement of visual acuity after surgery for nystagmus. Ophthalmology. 1993;100:1488–97.

    Article  CAS  PubMed  Google Scholar 

  61. Bietti BG, Bagolini B. Traitment medicochirurgical du nystagmus. Annee Ther Clin Ophtalmol. 1960;11:269–96.

    Google Scholar 

  62. von Noorden GV, Sprunger DT. Large rectus muscle recession for the treatment of congenital nystagmus. Arch Ophthalmol. 1991;109:221–4.

    Article  Google Scholar 

  63. Helveston EM, Ellis FD, Plager DA. Large recession of the horizontal recti for treatment of nystagmus. Ophthalmology. 1991;98:1302–5.

    Article  CAS  PubMed  Google Scholar 

  64. Datta H, Prasad S. Postequatorial horizontal rectus recession in the management of congenital nystagmus. Indian J Ophthalmol. 1994;42:203–6.

    CAS  PubMed  Google Scholar 

  65. Erbagci I, Gungor K, Bekir NA. Effectiveness of retroequatorial recession surgery in congenital nystagmus. Strabismus. 2004;12:35–40.

    Article  PubMed  Google Scholar 

  66. Boyle NJ, Dawson EL, Lee JP. Benefits of retroequatorial four horizontal muscle recession surgery in congenital idiopathic nystagmus in adults. J AAPOS. 2006;10:404–8.

    Article  PubMed  Google Scholar 

  67. Bagheri A, Farahi A, Yazdani S. The effect of bilateral horizontal rectus recession on visual acuity, ocular deviation or head posture in patients with nystagmus. Journal of AAPOS. 2005;9:433–7.

    Article  PubMed  Google Scholar 

  68. Hertle RW, Dell'Osso LF, Fitz Gibbon EJ, et al. Horizontal rectus tenotomy in patients with congenital nystagmus: results in 10 adults. Ophthalmology. 2003;110:2097–105.

    Article  PubMed  Google Scholar 

  69. Hertle RW, Dell'Osso LF, Fitz Gibbon EJ, et al. Horizontal rectus muscle tenotomy in children with infantile nystagmus syndrome: a pilot study. J Aapos. 2004;8:539–48.

    Article  PubMed  Google Scholar 

  70. Wang Z, Dell'Osso LF, Jacobs JB, et al. Effects of tenotomy on patients with infantile nystagmus syndrome: foveation improvement over a broadened visual field. J Aapos. 2006;10:552–60.

    Article  PubMed  Google Scholar 

  71. Dell’Osso L, Hertle RW, Williams RW, Jacobs JB. A new surgery for congenital nystagmus: effects of tenotomy on an achiasmatic canine and the role of extraocular proprioception. J AAPOS. 1999;3:166–82.

    Article  PubMed  Google Scholar 

  72. Wang ZI, Dell’Osso LF. Being “slow to see” is a dynamic visual function consequence of infantile nystagmus syndrome: model predictions and patient data identify stimulus timing as its cause. Vis Res. 2007;47:1550–60.

    Article  CAS  PubMed  Google Scholar 

  73. •• Hertle RW. Does eye muscle surgery improve vision in patients with infantile nystagmus syndrome? Ophthalmology. 2009;116(10):1837–8. Surgical interference with peripheral extraocular muscle or tendon enthesial proprioceptive nerve endings influence central ocular motor pathways, resulting in an improved INS oscillation

    Article  PubMed  Google Scholar 

  74. •• Thomas MG, Crosier M, Lindsay S, et al. Abnormal retinal development associated with FRMD7 mutations. Hum Mol Genet. 2014;23:4086–93. First time that abnormal afferent system development is associated with idiopathic infantile nystagmus using in-situ hybridization and OCT

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Holmstrom G, Bondeson ML, Eriksson U, Akerblom H, Larsson E. ‘Congenital’ nystagmus may hide various ophthalmic diagnoses. Acta Ophthalmol. 2014;92(5):412–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University of California San Diego, 9415 Campus Point Dr. #257, La Jolla, CA, 92037, USA

    Rohan Verma, Hema L. Ramkumar, Kang Zhang & David B. Granet

  2. Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, 92037, USA

    Kang Zhang

  3. Ratner Children’s Eye Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, 92037, USA

    Kang Zhang & David B. Granet

  4. Akron Children’s Hospital Vision Center, Akron Children’s Hospital, Akron, OH, 44302, USA

    Richard W. Hertle

  5. Northeast Ohio Medical University, Rootstown, OH, USA

    Richard W. Hertle

Authors
  1. Rohan Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hema L. Ramkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David B. Granet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard W. Hertle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rohan Verma.

Ethics declarations

Conflict of Interest

Rohan Verma, Hema Ramkumar, Kang Zhang, David Granet, and Richard Hertle declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Source of Funding

Supported by the National Eye Institute (NEI) Vision Research Core Grant P30EY022589 and an unrestricted grant by Research to Prevent Blindness, New York, NY.

Additional information

This article is part of the Topical Collection on Pediatric Ophthalmology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verma, R., Ramkumar, H.L., Zhang, K. et al. X-Linked Idiopathic Infantile Nystagmus (XLIIN): Case Report and Review of Literature. Curr Ophthalmol Rep 5, 128–135 (2017). https://doi.org/10.1007/s40135-017-0139-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40135-017-0139-y

Keywords

Search

Navigation