Congenital nystagmus Author: Doctor Christophe Orssaud1 Scientific Editor: Professor Jean-Louis Dufier Creation date: October 2003 1Service d'ophtalmologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 PARIS Cedex 15, FRANCE. [email protected] Abstract Key-words Disease name Definition/Diagnosis criteria Differential diagnosis Pathophysiology Clinical description Paraclinic testing and diagnosis Frequency Treatment Reference Abstract Idiopathic congenital nystagmus is defined as conjugated, spontaneous and involuntary ocular oscillations that appear at birth or during the first three months of life. This nystagmus persists throughout life. The frequency is estimated to 1 in 1500 births. Ocular oscillations are often symmetric and usually horizontal in 95% of patients. They can persist after eye closure, however, decrease of idiopathic congenital nystagmus have been reported during non-visual tasks. Nystagmus can be classified into different categories (Pendular nystagmus, horizontal unidirectional nystagmus, bi- directional nystagmus ) according to the characteristics of their oscillations: peak-to-peak amplitude, frequency, mean velocity, direction and period of foveation. This disorder is believed to be due to a primary abnormality in oculomotor control. Autosomal dominant, autosomal recessive, X-linked dominant and X-linked recessive modes of inheritance have been described. The gene that maps to chromosomes 6p12 (NYS2) is associated with autosomal dominant inheritance. The genes mapped to chromosome Xp11.4-p11.3 (NYS1) and Xq26-q27 are associated with X-linked congenital forms. There are evidences for a fourth gene in idiopathic congenital nystagmus. Complete ophthalmologic examination and electrophysiological study must be performed to rule out any ocular abnormalities causing bilateral visual deprivation or retinal dysfunction. Treatment of idiopathic congenital nystagmus aims at improving the vision. It includes correction of refractive errors, drugs and eye muscle surgery. Key-words Idiopathic congenital nystagmus, foveation periods, NYS2, NYS1, Xq26-q27 Disease name ocular oscillations that appear at birth or during Congenital motor nystagmus the first three months of life. This nystagmus Idiopathic congenital nystagmus persists throughout life. Definition/Diagnosis criteria Differential diagnosis Idiopathic congenital nystagmus is defined as Idiopathic congenital nystagmus must be conjugated, spontaneous and involuntary distinguished from sensory congenital Orssaud C. Congenital nystagmus. Orphanet Encyclopedia. October 2003. http://www.orpha.net/data/patho/GB/uk-nystagmus.pdf 1 nystagmus associated with congenital retinal congenital nystagmus. However, in some disease due to genetic disorder or with other families, with male-to-male transmission, abnormal conditions causing deprivation of the linkage to chromosome 6 was excluded, visual system. The most frequent excluded providing evidence for a fourth causative gene. diseases include aniridia with macular There is no candidate gene associated with hypoplasia, all forms of albinism, early retinal these different loci. dystrophies, congenital stationary night blindness which maps to chromosome Xp11.3, Clinical description achromatopsia, blue cone monochromatism Idiopathic congenital nystagmus is which maps to chromosome Xq28, bilateral characterized by conjugated, bilateral, optic nerve hypoplasia, chorio-retinal or spontaneous, involuntary and uncontrollable papillary coloboma, recessive optic atrophy. ocular oscillations. These oscillations are often Ophthalmologic examination and symmetric and usually horizontal in 95% of electrophysiological studies can easily rule out patients. Oscillations can persist after eye these retinal and optic nerve pathologies. In closure. However, decrease of idiopathic addition, sensory congenital nystagmus may congenital nystagmus have been reported result from bilateral congenital cataracts, which during non-visual tasks. Nystagmus can be are also easily excluded with ocular classified into different categories according to examination. Central nervous system the characteristics of their oscillations: peak-to- dysfunction must also be ruled out, since peak amplitude, frequency, mean velocity, neurological abnormalities are not encountered direction and period of foveation. in idiopathic congenital nystagmus. Pendular nystagmus is a rare form of idiopathic congenital nystagmus and is more Pathophysiology specific of youngest patients. Most of the Different hypotheses have been proposed to patients, especially after the age of 18 months, explain the mechanisms involved in idiopathic present with a jerk nystagmus, with congenital nystagmus. A defect in motor accelerating slow phase in eccentric gaze. control of visual fixation or an abnormal Horizontal unidirectional nystagmus is rare in development of fixation system of the brain idiopathic congenital nystagmus and without any detectable central nervous system characterized by oscillations beating always in abnormalities, as well as an instability of the the same direction. A bi-directional nystagmus neural integrator responsible for gaze holder is most often encountered, as the direction of may underlie the pathology. However, fixation oscillation changes according to gaze mechanisms appear to be functional in direction. Nystagmus beats to the right when congenital nystagmus since it is associated gaze is oriented to the right and to the left with strong fixation reflexes. In addition, when gaze is oriented to the left. In reversing idiopathic congenital nystagmus can increase zone of nystagmus direction, oscillations slow during fixation and decrease in non-visual down with reduced amplitude or disappear. tasks. Thus, it has been suggested that this Thus, visual acuity is better in this null zone nystagmus can result from an abnormal circuit and patients try to use it, inducing a torticollis. between the fixation system and ocular Null zone can be localized in primary position, stabilization systems. However, it is not yet in an eccentric position of gaze or in possible to link the waveform presentation in convergence. Some patients present with two idiopathic congenital nystagmus with an null zone, one in each gaze direction. etiology or an ocular motor system Visual acuity and contrast sensitivity are dysfunction. reduced during nystagmus, due to the Autosomal dominant, autosomal recessive, X- continuous shifting of images on the fovea that linked dominant and X-linked recessive modes is induced by ocular oscillations. In contrast to of inheritance have been described. However, what is observed during primary sensory the existence of dominant and recessive forms nystagmus, visual acuity is usually better in X-linked inheritance has not been clearly preserved in patients with idiopathic congenital established. In addition, penetrance could be nystagmus. and is sometimes normal. Visual incomplete in these X-linked forms. acuity ranges from 20/50 to 20/20, with a mean At least, 4 genes are suspected to be value of 20/30. However, visual acuity is associated with idiopathic congenital related to the duration of foveation periods. nystagmus. The gene that maps to Foveation periods are well preserved during chromosomes 6p12 (NYS2) is associated with idiopathic congenital nystagmus since slow autosomal dominant inheritance. The genes phases velocity allows the fixation system to mapped to chromosome Xp11.4-p11.3 (NYS1) prolong the fixation and the foveation when the and Xq26-q27 are associated with X-linked images fall on the fovea. The longer the Orssaud C. Congenital nystagmus. Orphanet Encyclopedia. October 2003. http://www.orpha.net/data/patho/GB/uk-nystagmus.pdf 2 foveation time the higher the visual acuity. In Other non-surgical techniques have been addition, a relationship exists between the proposed, such as the afferent stimulations of visual acuity and the eye position during the ophthalmic division of the trigeminal nerve foveation. A variability of eye position is or cutaneous stimulations. Pharmacological responsible for a decrease of visual acuity in treatment of idiopathic congenital nystagmus spite of long foveation periods. Patients do not has limited interest in the literature. An inhibitor perceived oscillopsia in idiopathic congenital of glutamate release, the Baclofen, can nystagmus except when new visual sensory improve the visual acuity in small series of conditions appear such as strabismus. patients. In cases of high eccentration of the null Paraclinic testing and diagnosis position, surgery for head posture can be Complete ophthalmologic examination must be achieved. Kestenbaum proposed to perform performed to rule out any ocular abnormalities recessions and/or resections of the four causing bilateral visual deprivation or retinal horizontal muscles in order to shift horizontally dysfunction. However, even when ocular the null position in primary position. examination is normal, an electrophysiological Recessions and/or resections of the four study with electroretinography and visual vertical muscles have been proposed when the evoked potentials is always necessary to affirm null zone must be shifted vertically. In torsional the absence of retinal or optic tract mull zone, the Spielmann procedure consists dysfunction. Neuro-imagery can be required in in a slanting or the insertion of the rectus case of nystagmus appearing during months muscles. after birth and without any evidence of ocular In order to improve visual