X-linked infantile nystagmus is a condition characterized by abnormal eye movements. Nystagmus is a term that refers to involuntary side-to-side, up-and-down, or circular movements of the eyes. In people with X-linked infantile nystagmus, the movements are typically side-to-side. In individuals with this condition, nystagmus is present at birth or develops within the first six months of life.
The abnormal eye movements may worsen when an affected person is feeling anxious or tries to stare directly at an object. Some affected individuals will experience involuntary changes in the direction of their eye movements (periodic alternating nystagmus). The severity of nystagmus varies, even among affected individuals within the same family. Sometimes, affected individuals will turn or tilt their head to compensate for the irregular eye movements. Individuals with X-linked infantile nystagmus may have other eye abnormalities. For example, the region at the back of the eye responsible for sharp central vision may be underdeveloped (foveal hypoplasia).
The incidence of X-linked infantile nystagmus is estimated to be 4.4 in 10,000 individuals.
Variants (also called mutations) in the FRMD7 gene cause X-linked infantile nystagmus. The FRMD7 gene provides instructions for making a protein whose exact function is unknown. This protein is found mostly in areas of the brain that control eye movement and in the light-sensitive tissue at the back of the eye (retina). Research suggests that FRMD7 gene variants cause nystagmus by disrupting the development of certain nerve cells in the brain and retina.
In some people with X-linked infantile nystagmus, no variant in the FRMD7 gene has been found. The genetic cause of the disorder is unknown in these individuals. Researchers believe that variants in at least one other gene, which has not been identified, can cause this disorder. Nystagmus can also occur in people with other X-linked eye conditions, such as X-linked ocular albinism. Such cases are caused by changes in genes associated with the particular condition.
X-linked infantile nystagmus is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In individuals with one X chromosome (typical for males), a variant in the only copy of the gene in each cell is sufficient to cause the condition. In people with two copies of the X chromosome (typical for females), one altered copy of the gene can cause the condition, although the features may be less severe than in individuals with two altered copies. Some of these individuals may have no signs or symptoms at all; approximately half of females with only one altered copy of the FRMD7 gene have no symptoms of this condition.
Other Names for This Condition
- Congenital motor nystagmus
- FRMD7-related infantile nystagmus
- Idiopathic infantile nystagmus
- X-linked congenital nystagmus
- X-linked idiopathic infantile nystagmus
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- He X, Gu F, Wang Z, Wang C, Tong Y, Wang Y, Yang J, Liu W, Zhang M, Ma X. A novel frameshift mutation in FRMD7 causing X-linked idiopathic congenital nystagmus. Genet Test. 2008 Dec;12(4):607-13. doi: 10.1089/gte.2008.0070. Citation on PubMed
- Kuht HJ, Maconachie GDE, Han J, Kessel L, van Genderen MM, McLean RJ, Hisaund M, Tu Z, Hertle RW, Gronskov K, Bai D, Wei A, Li W, Jiao Y, Smirnov V, Choi JH, Tobin MD, Sheth V, Purohit R, Dawar B, Girach A, Strul S, May L, Chen FK, Heath Jeffery RC, Aamir A, Sano R, Jin J, Brooks BP, Kohl S, Arveiler B, Montoliu L, Engle EC, Proudlock FA, Nishad G, Pani P, Varma G, Gottlob I, Thomas MG. Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study. Ophthalmology. 2022 Jun;129(6):708-718. doi: 10.1016/j.ophtha.2022.02.010. Epub 2022 Feb 11. Citation on PubMed
- Li N, Wang L, Cui L, Zhang L, Dai S, Li H, Chen X, Zhu L, Hejtmancik JF, Zhao K. Five novel mutations of the FRMD7 gene in Chinese families with X-linked infantile nystagmus. Mol Vis. 2008 Apr 18;14:733-8. Citation on PubMed or Free article on PubMed Central
- Sarvananthan N, Surendran M, Roberts EO, Jain S, Thomas S, Shah N, Proudlock FA, Thompson JR, McLean RJ, Degg C, Woodruff G, Gottlob I. The prevalence of nystagmus: the Leicestershire nystagmus survey. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5201-6. doi: 10.1167/iovs.09-3486. Epub 2009 May 20. Citation on PubMed
- Self J, Lotery A. A review of the molecular genetics of congenital Idiopathic Nystagmus (CIN). Ophthalmic Genet. 2007 Dec;28(4):187-91. doi: 10.1080/13816810701651233. Citation on PubMed
- Self JE, Shawkat F, Malpas CT, Thomas NS, Harris CM, Hodgkins PR, Chen X, Trump D, Lotery AJ. Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus. Arch Ophthalmol. 2007 Sep;125(9):1255-63. doi: 10.1001/archopht.125.9.1255. Citation on PubMed
- Shiels A, Bennett TM, Prince JB, Tychsen L. X-linked idiopathic infantile nystagmus associated with a missense mutation in FRMD7. Mol Vis. 2007 Nov 29;13:2233-41. Citation on PubMed
- Tarpey P, Thomas S, Sarvananthan N, Mallya U, Lisgo S, Talbot CJ, Roberts EO, Awan M, Surendran M, McLean RJ, Reinecke RD, Langmann A, Lindner S, Koch M, Jain S, Woodruff G, Gale RP, Bastawrous A, Degg C, Droutsas K, Asproudis I, Zubcov AA, Pieh C, Veal CD, Machado RD, Backhouse OC, Baumber L, Constantinescu CS, Brodsky MC, Hunter DG, Hertle RW, Read RJ, Edkins S, O'Meara S, Parker A, Stevens C, Teague J, Wooster R, Futreal PA, Trembath RC, Stratton MR, Raymond FL, Gottlob I. Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nat Genet. 2006 Nov;38(11):1242-4. doi: 10.1038/ng1893. Epub 2006 Oct 1. Erratum In: Nat Genet. 2011 Jul;43(7):720. Bastawrous, Andrew [added]. Citation on PubMed or Free article on PubMed Central
- Thomas MG, Crosier M, Lindsay S, Kumar A, Araki M, Leroy BP, McLean RJ, Sheth V, Maconachie G, Thomas S, Moore AT, Gottlob I. Abnormal retinal development associated with FRMD7 mutations. Hum Mol Genet. 2014 Aug 1;23(15):4086-93. doi: 10.1093/hmg/ddu122. Epub 2014 Mar 31. Citation on PubMed
- Thomas MG, Crosier M, Lindsay S, Kumar A, Thomas S, Araki M, Talbot CJ, McLean RJ, Surendran M, Taylor K, Leroy BP, Moore AT, Hunter DG, Hertle RW, Tarpey P, Langmann A, Lindner S, Brandner M, Gottlob I. The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain. 2011 Mar;134(Pt 3):892-902. doi: 10.1093/brain/awq373. Epub 2011 Feb 8. Citation on PubMed
- Thomas MG, Maconachie G, Hisaund M, Gottlob I. FRMD7-Related Infantile Nystagmus. 2009 Feb 12 [updated 2018 Aug 16]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK3822/ Citation on PubMed
- Thomas MG, Maconachie G, Sheth V, McLean RJ, Gottlob I. Development and clinical utility of a novel diagnostic nystagmus gene panel using targeted next-generation sequencing. Eur J Hum Genet. 2017 Jun;25(6):725-734. doi: 10.1038/ejhg.2017.44. Epub 2017 Apr 5. Citation on PubMed
- Thomas S, Proudlock FA, Sarvananthan N, Roberts EO, Awan M, McLean R, Surendran M, Kumar AS, Farooq SJ, Degg C, Gale RP, Reinecke RD, Woodruff G, Langmann A, Lindner S, Jain S, Tarpey P, Raymond FL, Gottlob I. Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7. Brain. 2008 May;131(Pt 5):1259-67. doi: 10.1093/brain/awn046. Epub 2008 Mar 27. Citation on PubMed
- Zhang B, Liu Z, Zhao G, Xie X, Yin X, Hu Z, Xu S, Li Q, Song F, Tian J, Luo W, Ding M, Yin J, Xia K, Xia J. Novel mutations of the FRMD7 gene in X-linked congenital motor nystagmus. Mol Vis. 2007 Sep 13;13:1674-9. Citation on PubMed
- Zhang Q, Xiao X, Li S, Guo X. FRMD7 mutations in Chinese families with X-linked congenital motor nystagmus. Mol Vis. 2007 Aug 3;13:1375-8. Citation on PubMed