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Nystagmus 1, congenital, X-linked(NYS1; IIN, FORMERLY)

MedGen UID:
333352
Concept ID:
C1839580
Disease or Syndrome
Synonyms: Infantile nystagmus, X-linked; Nystagmus 1, congenital, X- linked; NYSTAGMUS 1, INFANTILE, X-LINKED; Nystagmus, congenital motor, 1; NYSTAGMUS, INFANTILE IDIOPATHIC; NYSTAGMUS, INFANTILE PERIODIC ALTERNATING, X-LINKED
 
Gene (location): FRMD7 (Xq26.2)
 
Monarch Initiative: MONDO:0010693
OMIM®: 310700

Disease characteristics

Excerpted from the GeneReview: FRMD7-Related Infantile Nystagmus
FRMD7-related infantile nystagmus (FIN) is characterized by either the onset of horizontal, conjugate, gaze-dependent nystagmus in the first six months of life or periodic alternating nystagmus (with cyclical changes of nystagmus direction) of infantile onset. Binocular vision and color vision are normal and visual acuity is typically better than 6/12. An abnormal head posture is seen in approximately 15% of affected individuals. The eyes are structurally normal and electrophysiologic studies (e.g., visual evoked potential, electroretinogram) are normal. Affected females report slightly better visual acuity than affected males; however, no differences between males and females in the amplitude, frequency, and waveform of nystagmus are observed. [from GeneReviews]
Authors:
Mervyn G Thomas  |  Gail Maconachie  |  Michael Hisaund, et. al.   view full author information

Additional descriptions

From OMIM
Classic congenital or infantile nystagmus presents as conjugate, horizontal oscillations of the eyes, in primary or eccentric gaze, often with a preferred head turn or tilt. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. Eye movement recordings reveal that infantile nystagmus is predominantly a horizontal jerk waveform, with a diagnostic accelerating velocity slow phase. However, pendular and triangular waveforms may also be present. The nystagmus may rarely be vertical. As these patients often have normal visual acuity, it is presumed that the nystagmus represents a primary defect in the parts of the brain responsible for ocular motor control; thus the disorder has sometimes been termed 'congenital motor nystagmus' (Tarpey et al., 2006; Shiels et al., 2007). Congenital nystagmus may also be a feature of other ocular diseases, such as albinism (see, e.g., OCA1A, 203100), achromatopsia (see, e.g., ACHM3, 262300), and Leber congenital amaurosis (see, e.g., LCA1, 204000). Congenital nystagmus is associated with at least 3 X-linked disorders: Nettleship-Falls ocular albinism (OA1; 300500), which maps to Xp22.3; complete congenital stationary night blindness (CSNB1; 310500), which maps to Xp11.4; and blue-cone monochromatism (CBBM; 303700), which maps to Xq28. Genetic Heterogeneity of Congenital Nystagmus Two other X-linked forms of congenital nystagmus have been reported: NYS5 (300589), which maps to Xp11.4-p11.3, and NYS6 (300814), which is caused by mutation in the GPR143 gene (300808) on Xp22.3. Autosomal dominant forms have been mapped to chromosomes 6p12 (NYS2; 164100), 7p11 (NYS3; 608345), and 1q31-q32 (NYS7; 614826). An autosomal recessive form (NYS8; 257400) is caused by mutation in the ROBO1 gene (602430) on chromosome 3p12. A disorder formerly designated NYS4 has been reclassified; see 193003.  http://www.omim.org/entry/310700
From MedlinePlus Genetics
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).   https://medlineplus.gov/genetics/condition/x-linked-infantile-nystagmus

Clinical features

From HPO
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Horizontal nystagmus
MedGen UID:
124399
Concept ID:
C0271385
Disease or Syndrome
Nystagmus consisting of horizontal to-and-fro eye movements.
Pendular nystagmus
MedGen UID:
78770
Concept ID:
C0271388
Disease or Syndrome
Rhythmic, involuntary sinusoidal oscillations of one or both eyes. The waveform of pendular nystagmus may occur in any direction.
Congenital nystagmus
MedGen UID:
195995
Concept ID:
C0700501
Congenital Abnormality
Nystagmus dating from or present at birth.
Mildly reduced visual acuity
MedGen UID:
1671080
Concept ID:
C4732817
Finding
Mild reduction of the ability to see. On the 6m visual acuity scale, mild reduction is defined as less than 6/12 but at least 6/18. On the 20ft visual acuity scale, mild reduction is defined as less than 20/40 but at least 20/70. On the decimal visual acuity scale, mild reduction is defined as less than 0.5 but at least 0.3.

Professional guidelines

PubMed

Choi JH, Jung JH, Oh EH, Shin JH, Kim HS, Seo JH, Choi SY, Kim MJ, Choi HY, Lee C, Choi KD
Invest Ophthalmol Vis Sci 2018 Jun 1;59(7):3181-3188. doi: 10.1167/iovs.18-24207. PMID: 30025138

Recent clinical studies

Etiology

Choi JH, Jung JH, Oh EH, Shin JH, Kim HS, Seo JH, Choi SY, Kim MJ, Choi HY, Lee C, Choi KD
Invest Ophthalmol Vis Sci 2018 Jun 1;59(7):3181-3188. doi: 10.1167/iovs.18-24207. PMID: 30025138
Dunn MJ, Margrain TH, Woodhouse JM, Erichsen JT
Invest Ophthalmol Vis Sci 2015 Aug;56(9):5094-101. doi: 10.1167/iovs.15-16977. PMID: 26241396
AlMoallem B, Bauwens M, Walraedt S, Delbeke P, De Zaeytijd J, Kestelyn P, Meire F, Janssens S, van Cauwenbergh C, Verdin H, Hooghe S, Kumar Thakur P, Coppieters F, De Leeneer K, Devriendt K, Leroy BP, De Baere E
Invest Ophthalmol Vis Sci 2015 Feb 12;56(3):1701-10. doi: 10.1167/iovs.14-15938. PMID: 25678693
Leguire LE, Kashou NH, Fogt N, Smith MA, Lewis JR, Kulwin R, Rogers GL
J Pediatr Ophthalmol Strabismus 2011 Nov-Dec;48(6):347-56. Epub 2011 Jan 25 doi: 10.3928/01913913-20110118-03. PMID: 21261242

Diagnosis

Jackson D, Malka S, Harding P, Palma J, Dunbar H, Moosajee M
Am J Med Genet C Semin Med Genet 2020 Sep;184(3):578-589. Epub 2020 Aug 23 doi: 10.1002/ajmg.c.31837. PMID: 32830442Free PMC Article
Choi JH, Jung JH, Oh EH, Shin JH, Kim HS, Seo JH, Choi SY, Kim MJ, Choi HY, Lee C, Choi KD
Invest Ophthalmol Vis Sci 2018 Jun 1;59(7):3181-3188. doi: 10.1167/iovs.18-24207. PMID: 30025138
AlMoallem B, Bauwens M, Walraedt S, Delbeke P, De Zaeytijd J, Kestelyn P, Meire F, Janssens S, van Cauwenbergh C, Verdin H, Hooghe S, Kumar Thakur P, Coppieters F, De Leeneer K, Devriendt K, Leroy BP, De Baere E
Invest Ophthalmol Vis Sci 2015 Feb 12;56(3):1701-10. doi: 10.1167/iovs.14-15938. PMID: 25678693
Zhu Y, Zhuang J, Ge X, Zhang X, Wang Z, Sun J, Yang J, Gu F
Sci Rep 2013 Oct 30;3:3084. doi: 10.1038/srep03084. PMID: 24169426Free PMC Article
Haratz K, Viñals F, Lev D, Feit H, Ben-Sira L, Lerman-Sagie T, Malinger G
Ultrasound Obstet Gynecol 2011 Dec;38(6):646-51. Epub 2011 Nov 11 doi: 10.1002/uog.9050. PMID: 21584889

Therapy

Guo Y, Song Z, Xu H, Yi J, Zheng W, Xiang H, Deng X, Lv H, Gao K, Qi Y, Deng H
Can J Ophthalmol 2014 Feb;49(1):50-3. doi: 10.1016/j.jcjo.2013.09.001. PMID: 24513357

Prognosis

AlMoallem B, Bauwens M, Walraedt S, Delbeke P, De Zaeytijd J, Kestelyn P, Meire F, Janssens S, van Cauwenbergh C, Verdin H, Hooghe S, Kumar Thakur P, Coppieters F, De Leeneer K, Devriendt K, Leroy BP, De Baere E
Invest Ophthalmol Vis Sci 2015 Feb 12;56(3):1701-10. doi: 10.1167/iovs.14-15938. PMID: 25678693
Haratz K, Viñals F, Lev D, Feit H, Ben-Sira L, Lerman-Sagie T, Malinger G
Ultrasound Obstet Gynecol 2011 Dec;38(6):646-51. Epub 2011 Nov 11 doi: 10.1002/uog.9050. PMID: 21584889

Clinical prediction guides

Choi JH, Jung JH, Oh EH, Shin JH, Kim HS, Seo JH, Choi SY, Kim MJ, Choi HY, Lee C, Choi KD
Invest Ophthalmol Vis Sci 2018 Jun 1;59(7):3181-3188. doi: 10.1167/iovs.18-24207. PMID: 30025138
AlMoallem B, Bauwens M, Walraedt S, Delbeke P, De Zaeytijd J, Kestelyn P, Meire F, Janssens S, van Cauwenbergh C, Verdin H, Hooghe S, Kumar Thakur P, Coppieters F, De Leeneer K, Devriendt K, Leroy BP, De Baere E
Invest Ophthalmol Vis Sci 2015 Feb 12;56(3):1701-10. doi: 10.1167/iovs.14-15938. PMID: 25678693
Haratz K, Viñals F, Lev D, Feit H, Ben-Sira L, Lerman-Sagie T, Malinger G
Ultrasound Obstet Gynecol 2011 Dec;38(6):646-51. Epub 2011 Nov 11 doi: 10.1002/uog.9050. PMID: 21584889
Leguire LE, Kashou NH, Fogt N, Smith MA, Lewis JR, Kulwin R, Rogers GL
J Pediatr Ophthalmol Strabismus 2011 Nov-Dec;48(6):347-56. Epub 2011 Jan 25 doi: 10.3928/01913913-20110118-03. PMID: 21261242

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