Nystagmus 1, Congenital, X-linked

Clinical Characteristics
Ocular Features: 

Congenital nystagmus is a feature of numerous ocular and systemic disorders.  Isolated idiopathic congenital nystagmus (CN), however, refers to a diverse group of abnormal eye movements which are identified usually in the first 6 months of life when no other ocular abnormalities are present.  Horizontal eye movements are typical, but vertical and rotary eye movements have also been reported.  If the nystagmus is horizontal, the eye movement is usually "to-and-fro".   In general, as the patient gets older, the amplitude of the nystagmus decreases and the frequency of the nystagmus increases, particularly when the patient tries to fixate or look directly at an object. This nystagmus can increase in size and frequency when the patient is tired, sick, or fatigued.  Some very young patients are noted to have head nodding or head shaking, but these usually disappear over time. Vision is reduced and varies through the day. Balance may also be affected.  Many patients have a "null point" where the eye movement is reduced and vision is improved.  They may alter their head position in an effort to maximize their acuity.

Strabismus and amblyopia often develop.

Systemic Features: 

No consistent systemic abnormalities have been reported.

Genetics

Different heritable patterns of idiopathic congenital nystagmus, including autosomal dominant and recessive, and X-linked recessive, have been found.  A variety of mutations in the FRMD7 (Xq26.2) gene (containing 12 exons) have been identified in many families with an X-linked recessive pattern. 

Another mutation associated with X-linked congenital nystagmus is GPR143 at Xp22.3 causing NYS6 (300814).  A locus at Xp11.4-p11.3  contains an as yet unknown mutation responsible for an infantile periodic alternating type: NYS5 (300589). 

Several autosomal dominant forms have been linked to chromosomal regions 6p12 (NYS2; 164100), 7p11 (NYS3, 608345), 13q (NYS4, 193003), 1q31.3-q32.1, and NYS7 (614826).  Autosomal recessive inheritance has been proposed for several pedigrees but adequate documentation is lacking (see 257400).

Treatment
Treatment Options: 

Congenital nystagmus cannot be cured.  However, several treatments may be beneficial.  Glasses and contact lenses, and, occasionally, extraocular muscle surgery may be helpful.  The latter should be considered especially when patients adopt a consistent head position for best vision.  This avoids long-term secondary changes in neck muscles and many individuals experience an improvement of two or more lines in visual acuity.  Low vision aids should be offered.

References
Article Title: 

Incidence and Types of Pediatric Nystagmus

Nash DL, Diehl NN, Mohney BG. Incidence and Types of Pediatric Nystagmus. Am J Ophthalmol. 2017 Jul 19. pii: S0002-9394(17)30301-X. doi: 10.1016/j.ajo.2017.07.006. [Epub ahead of print].

PubMed ID: 
28734813

References

Nash DL, Diehl NN, Mohney BG. Incidence and Types of Pediatric Nystagmus. Am J Ophthalmol. 2017 Jul 19. pii: S0002-9394(17)30301-X. doi: 10.1016/j.ajo.2017.07.006. [Epub ahead of print].

PubMedID: 28734813

Li L, Xiao X, Yi C, Jiao X, Guo X, Hejtmancik JF, Zhang Q. Confirmation and refinement of an autosomal dominant congenital motor nystagmus locus in chromosome 1q31.3-q32.1. J Hum Genet. 2012 Aug 23. [Epub ahead of print] PubMed PMID: 22914672.

PubMedID: 22914672

Abel, L.A.: Infantile nystagmus: current concepts in diagnosis and management.  Clin. Exp. Optom. 89: 57-65, 2006.

PubMedID: 16494607

Self, J., and Lotery, A.: The molecular genetics of congenital idiopathic nystagmus.  Semin. Ophthalmol.  21: 87-90, 2006.

PubMedID: 16702075

Tarpey, P., Thomas, S., Sarvananthan, N., Mallya, U., Lisgo, S., Talbot, C.J., Roberts, E.O., Awan, M., Surendran, M., McLean, R.J., Reinecke, R.D., Langmann, A., et al.: Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.  Nature Genet. 38: 1242-1244, 2006.

PubMedID: 17013395

Hertle, R.W., Yang, D., Kelly, K., Hill, V.M., and Seward, A.:  X-linked infantile periodic alternating nystagmus. Ophthal. Genet. 26: 77-84, 2005.

PubMedID: 16020310