Congenital nystagmus

Author: Doctor Christophe Orssaud

1

Scientific Editor: Professor Jean-Louis Dufier

Creation date: October 2003
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Service d'ophtalmologie, Hpital Europen Georges Pompidou, 20 rue Leblanc, 75908 PARIS Cedex
15, FRANCE. Christophe.Orssaud@hop.egp.ap-hop-paris.fr
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
Congenital motor nystagmus
Idiopathic congenital nystagmus

Definition/Diagnosis criteria
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.

Differential diagnosis
Idiopathic congenital nystagmus must be
distinguished from sensory congenital

Orssaud C. Congenital nystagmus. Orphanet Encyclopedia. October 2003.
http://www.orpha.net/data/patho/GB/uk-nystagmus.pdf
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nystagmus associated with congenital retinal
disease due to genetic disorder or with other
abnormal conditions causing deprivation of the
visual system. The most frequent excluded
diseases include aniridia with macular
hypoplasia, all forms of albinism, early retinal
dystrophies, congenital stationary night
blindness which maps to chromosome Xp11.3,
achromatopsia, blue cone monochromatism
which maps to chromosome Xq28, bilateral
optic nerve hypoplasia, chorio-retinal or
papillary coloboma, recessive optic atrophy.
Ophthalmologic examination and
electrophysiological studies can easily rule out
these retinal and optic nerve pathologies. In
addition, sensory congenital nystagmus may
result from bilateral congenital cataracts, which
are also easily excluded with ocular
examination. Central nervous system
dysfunction must also be ruled out, since
neurological abnormalities are not encountered
in idiopathic congenital nystagmus.

Pathophysiology
Different hypotheses have been proposed to
explain the mechanisms involved in idiopathic
congenital nystagmus. A defect in motor
control of visual fixation or an abnormal
development of fixation system of the brain
without any detectable central nervous system
abnormalities, as well as an instability of the
neural integrator responsible for gaze holder
may underlie the pathology. However, fixation
mechanisms appear to be functional in
congenital nystagmus since it is associated
with strong fixation reflexes. In addition,
idiopathic congenital nystagmus can increase
during fixation and decrease in non-visual
tasks. Thus, it has been suggested that this
nystagmus can result from an abnormal circuit
between the fixation system and ocular
stabilization systems. However, it is not yet
possible to link the waveform presentation in
idiopathic congenital nystagmus with an
etiology or an ocular motor system
dysfunction.
Autosomal dominant, autosomal recessive, X-
linked dominant and X-linked recessive modes
of inheritance have been described. However,
the existence of dominant and recessive forms
in X-linked inheritance has not been clearly
established. In addition, penetrance could be
incomplete in these X-linked forms.
At least, 4 genes are suspected to be
associated with idiopathic congenital
nystagmus. 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 nystagmus. However, in some
families, with male-to-male transmission,
linkage to chromosome 6 was excluded,
providing evidence for a fourth causative gene.
There is no candidate gene associated with
these different loci.

Clinical description
Idiopathic congenital nystagmus is
characterized by conjugated, bilateral,
spontaneous, involuntary and uncontrollable
ocular oscillations. These oscillations are often
symmetric and usually horizontal in 95% of
patients. Oscillations 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 according to
the characteristics of their oscillations: peak-to-
peak amplitude, frequency, mean velocity,
direction and period of foveation.
Pendular nystagmus is a rare form of
idiopathic congenital nystagmus and is more
specific of youngest patients. Most of the
patients, especially after the age of 18 months,
present with a jerk nystagmus, with
accelerating slow phase in eccentric gaze.
Horizontal unidirectional nystagmus is rare in
idiopathic congenital nystagmus and
characterized by oscillations beating always in
the same direction. A bi-directional nystagmus
is most often encountered, as the direction of
oscillation changes according to gaze
direction. Nystagmus beats to the right when
gaze is oriented to the right and to the left
when gaze is oriented to the left. In reversing
zone of nystagmus direction, oscillations slow
down with reduced amplitude or disappear.
Thus, visual acuity is better in this null zone
and patients try to use it, inducing a torticollis.
Null zone can be localized in primary position,
in an eccentric position of gaze or in
convergence. Some patients present with two
null zone, one in each gaze direction.
Visual acuity and contrast sensitivity are
reduced during nystagmus, due to the
continuous shifting of images on the fovea that
is induced by ocular oscillations. In contrast to
what is observed during primary sensory
nystagmus, visual acuity is usually better
preserved in patients with idiopathic congenital
nystagmus. and is sometimes normal. Visual
acuity ranges from 20/50 to 20/20, with a mean
value of 20/30. However, visual acuity is
related to the duration of foveation periods.
Foveation periods are well preserved during
idiopathic congenital nystagmus since slow
phases velocity allows the fixation system to
prolong the fixation and the foveation when the
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
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foveation time the higher the visual acuity. In
addition, a relationship exists between the
visual acuity and the eye position during
foveation. A variability of eye position is
responsible for a decrease of visual acuity in
spite of long foveation periods. Patients do not
perceived oscillopsia in idiopathic congenital
nystagmus except when new visual sensory
conditions appear such as strabismus.

Paraclinic testing and diagnosis
Complete ophthalmologic examination must be
performed to rule out any ocular abnormalities
causing bilateral visual deprivation or retinal
dysfunction. However, even when ocular
examination is normal, an electrophysiological
study with electroretinography and visual
evoked potentials is always necessary to affirm
the absence of retinal or optic tract
dysfunction. Neuro-imagery can be required in
case of nystagmus appearing during months
after birth and without any evidence of ocular
pathology or electrophysiological abnormality.
Eye movement recordings are useful to
characterize the nystagmus. They provide
information on amplitude, frequency and mean
velocity as well as the aspect or direction of
the waveforms. Triangular waveforms are most
often encountered in younger children and
pendular nystagmus in patients less than 18
months.

Frequency
The frequency of idiopathic congenital
nystagmus is estimated to 1 in 1500 births. X-
linked mode of inheritance is probably the
most common form of idiopathic congenital
nystagmus.

Treatment
The treatment of idiopathic congenital
nystagmus aims at improving the vision. All
refractive errors must be first corrected, and
require an objective refraction after
cycloplegia. Optic lens are often a better way
to correct these refractive errors since they
move with the eyes during ocular oscillations.
However, prismatic spectacles can be used
when the null region is eccentric, in order to
shift the visual scene laterally and to reduce
the torticollis. But, their indication is limited to
small eccentration of the null position due to
reduction and distortion of vision they induce
when their value is too important. The base of
the prisms must be in the same direction on
both eyes, away from the null position. Base
out prisms may be used to damp idiopathic
congenital nystagmus during distance fixation
in patients with null zone in convergence.
Other non-surgical techniques have been
proposed, such as the afferent stimulations of
the ophthalmic division of the trigeminal nerve
or cutaneous stimulations. Pharmacological
treatment of idiopathic congenital nystagmus
has limited interest in the literature. An inhibitor
of glutamate release, the Baclofen, can
improve the visual acuity in small series of
patients.
In cases of high eccentration of the null
position, surgery for head posture can be
achieved. Kestenbaum proposed to perform
recessions and/or resections of the four
horizontal muscles in order to shift horizontally
the null position in primary position.
Recessions and/or resections of the four
vertical muscles have been proposed when the
null zone must be shifted vertically. In torsional
mull zone, the Spielmann procedure consists
in a slanting or the insertion of the rectus
muscles.
In order to improve visual acuity, different
authors have proposed to perform a large
recession of all horizontal muscles. Such
procedures decrease the intensity of the
oscillations of idiopathic congenital nystagmus.
A good result however is difficult to obtain and
iterative surgical procedures are often
necessary.

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Orssaud C. Congenital nystagmus. Orphanet Encyclopedia. October 2003.
http://www.orpha.net/data/patho/GB/uk-nystagmus.pdf
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