Journal of Binocular Vision and Ocular Motility

ISSN: 2576-117X (Print) 2576-1218 (Online) Journal homepage: http://www.tandfonline.com/loi/uaoj21

Infantile and Early Acquired Ophthalmoplegic

Syndromes

David G. Hunter

To cite this article: David G. Hunter (2018) Infantile and Early Acquired Ophthalmoplegic
Syndromes, Journal of Binocular Vision and Ocular Motility, 68:1, 7-9, DOI:
10.1080/2576117X.2017.1416039

To link to this article: https://doi.org/10.1080/2576117X.2017.1416039

Published online: 17 Jan 2018.

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JOURNAL OF BINOCULAR VISION AND OCULAR MOTILITY
2018, VOL. 68, NO. 1, 7–9
https://doi.org/10.1080/2576117X.2017.1416039

AAO/AOC/AACO ANNUAL SYMPOSIUM

Infantile and Early Acquired Ophthalmoplegic Syndromes

David G. Hunter, MD, PhDa,b
a
Department of Ophthalmology, Boston Children’s Hospital, Boston, Massachusetts; bDepartment of Ophthalmology, Harvard Medical
School, Boston, Massachusetts

ABSTRACT KEYWORDS
Ophthalmoplegia is rare in infants and may present either as a static or a progressing deficit. In Ophthalmoplegia;
this report, I will summarize the major causes of ophthalmoplegia when it presents in infancy or myasthenia; strabismus;
early childhood. Strategies for narrowing the differential diagnosis will also be considered. migraine

Introduction disorders (CCDDs), agenesis or anomalies of the

extraocular muscles, or congenital myopathy.
When an infant presents with strabismus associated with
The clinical features of the CCDDs were reviewed by
limitation of eye movements, the differential diagnosis is
Oystreck.3 Briefly, the main conditions to consider include
less extensive than what might be encountered in older
congenital cranial nerve palsy, Duane syndrome, congenital
children and adults. In this report, I review the potential
fibrosis of the extraocular muscles, Moebius syndrome, or
causes of ophthalmoplegia in infants. Ophthalmoplegia in
one of the various other CCDDs. Many of the CCDDs have
older children and adults is reviewed by Roper-Hall else-
Mendelian inheritance and have now been defined geneti-
where in this edition.1
cally, as reviewed by Whitman and Engle.4
The definition of ophthalmoplegia and the funda-
Ophthalmoplegia may present in infancy as a result of
mentals of evaluation were detailed by Dietz.2 Of note,
anomalous extraocular muscle development. Many of
when ophthalmoplegia is complete, the motility deficit
these cases have been reported in association with cranio-
will be visibly apparent on testing of gross eye move-
facial malformations, though early reports were based on
ments; however, when ophthalmoplegia is incomplete,
intraoperative findings and did not include imaging.5
eye movements may appear full, and the change in
With continued advances in imaging, cases previously
measurements in different directions may be the easiest
diagnosed as “agenesis” might more likely have been
way to detect the relative limitation of movement.
characterized as “anomalous development,” and complete
In infants, likely causes of ophthalmoplegia can be nar-
absence of extraocular muscles is probably quite rare.6
rowed down by asking a few key questions: Is the limitation
Aplastic or hypoplastic extraocular muscles may also
static or progressive? Are the findings stable or variable? Is
occur in the absence of craniofacial malformations7 or
the limitation symmetric or asymmetric? Is there ptosis?
in association with other congenital anomalies.8
Are pupil anomalies present? Does the patient have gener-
In congenital myopathy, the muscles and tendons
alized weakness or other systemic abnormalities? Does the
may appear normal on a gross structural level, and
child have episodes of irritability as an indication of pain?
innervation may be normal as well, but biopsy shows
myopathy. While some congenital myopathies, espe-
Static ophthalmoplegia in infants cially the most severe forms, have a static presentation
with complete loss of motility, most have progressive
Given the scrutiny that most parents apply to their symptomatology9 and are therefore discussed with the
new infants and the relatively obvious misalignment other progressive forms of ophthalmoplegia below.
or anomalous head posture that can occur when
ophthalmoplegia is present, it is generally possible to
determine whether ophthalmoplegia is static or pro- Progressive ophthalmoplegia in infants
gressive at the initial visit. Causes of static ophthalmo- Causes of progressive ophthalmoplegia in infants
plegia include congenital cranial dysinnervation include ophthalmoplegic migraine, neurodegenerative

CONTACT David G. Hunter david.hunter@childrens.harvard.edu Boston Children’s Hospital, 300 Longwood Avenue, Fegan 4, Boston, MA.
Presented as part of a symposium, Ophthalmoplegia: When the Eyes Don't Move, at the 2017 AAO Annual Meeting, New Orleans, LA.
© 2018 American Orthoptic Journal Inc.
8 D. G. HUNTER

disease, progressive myopathies including some forms one study reporting a preponderance in boys.21
of muscular dystrophy, and childhood myasthenia. Autoimmune testing may be performed as in adults,
While most cases of ophthalmoplegic migraine first testing for anti-AChR and anti-MuSK (muscle-specific
develop before age 10, at least three cases have been kinase) antibodies. A congenital myasthenic syndrome
reported in infants under 6 months of age.10–12 To meet genetic testing panel (which includes sequencing of 20
diagnostic criteria, a migraine-like headache must or more genes) may be submitted to confirm a genetic
occur in association with paresis of the third, fourth, etiology.20 If laboratory testing is negative and clinical
and/or sixth cranial nerves in the absence of structural suspicion remains strong, electromyography with repe-
pathology, though inflammation of the involved cranial titive nerve simulation may be considered, though this
nerve may be seen at the brainstem exit at the time of may only be positive in 20% of patients.19 An empiric
diagnosis. The ophthalmoplegia may occur up to 4 days trial of pyridostigmine (starting at 3.5 mg/kg/day
after onset of headache and still meet diagnostic cri- divided in three doses and increasing to a maximum
teria. While migraine headache is difficult to diagnose of 7 mg/kg/day) may be initiated as both a diagnostic
in an infant, irritability or vomiting (again in the and therapeutic maneuver.
absence of structural disease) may serve as a proxy. Infantile botulism, acquired from breast milk, is
Recurrence is common, and with repeated recurrence, cause of a severe, acute, myasthenia-like ophthalmople-
patients may be left with subtle long-term deficits.10 gia in infants. Unlike infantile myasthenia gravis, which
Neurodegenerative disease, including spinocerebellar may present with isolated strabismus and ptosis, infants
ataxia (SCA; most notably SCA type 2), can have an with botulism will have feeding and respiratory diffi-
onset as early as 2 months of age in rare cases.13,14 This culties as well as bilateral cycloplegia.
early presentation of SCA2 is often associated with
developmental delay and early onset ataxia, but in one
case, presentation was at 2 months of age, with devel- Conclusion
opmental delay noted at 6 months of age while ataxia CCDDs, extraocular muscle dysgenesis, and pro-
did not present until age 7 years.15 The cognitive dete- found congenital myopathy should be considered
rioration in SCA2 is progressive. SCA7 has also been when static ophthalmoplegia presents at birth.
associated with ophthalmoplegia, but patients with Episodic ophthalmoplegia could be ophthalmoplegic
infantile onset tend to have profound hypotonia and migraine, while acute and profound ophthalmoplegia
other signs of myopathy.16 in association with respiratory distress could be
Other forms of muscular dystrophy and myopathy botulism. Progressive ophthalmoplegia with a vari-
that have been associated with ophthalmoplegia include able course or in association with ptosis raises the
myotonic muscular dystrophy type 1 and myotubular possibility of myasthenia, while ophthalmoplegia
myopathy. When these conditions present in infancy, with relentless progression to systemic weakness or
the motility disturbance is secondary to the profound in association with generalized weakness could be
hypotonia and not observed as a presenting symptom. associated with neurodegenerative disease, muscular
Myotubular myopathy is X-linked recessive and asso- dystrophy, or other rare, progressive myopathies.
ciated with mutations in the MTM-1 gene. Patients will Nonsurgical treatment of ophthalmoplegia in chil-
have profound facial weakness with ptosis in addition dren and adults is reviewed by Arnoldi,22 and surgi-
to the systemic hypotonia. Nearly all patients with cal management is reviewed by Archer23 elsewhere in
infantile onset require respiratory support at birth, this issue. Treatment of each of these conditions is
and mortality is high.17 Mitochondrial myopathies challenging, and by necessity must be context-
rarely present in infancy and are discussed in detail dependent.
by Roper-Hall1 and McClelland.18
Myasthenia has an infantile onset in 7–10% of
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