Three-year observation of children 12 to 35 months old with untreated intermittent exotropia.

PURPOSE: To describe the clinical course of untreated intermittent exotropia (IXT) in children 12-35 months of age followed for 3 years. METHODS: We enrolled 97 children 12-35 months of age with previously untreated IXT who had been randomly assigned to the observation arm of a randomised trial of short-term occlusion versus observation. Participants were observed unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, and 6-month intervals thereafter for 3 years. The primary outcome was deterioration of the IXT by 3 years, defined as (1) a constant exotropia ≥10 prism dioptres (∆) at distance and near (i.e., motor deterioration) or (2) treatment prescribed despite not having met motor deterioration. The primary analysis used the Kaplan-Meier method to determine the cumulative proportion of participants meeting deterioration by three years and 95% confidence interval (CI). RESULTS: The cumulative probability of deterioration by 3 years was 28% (95% CI = 20%-39%). Of the 24 participants meeting the primary outcome of deterioration, seven met motor deterioration and 17 were prescribed treatment without meeting motor deterioration. The cumulative probability of motor deterioration by 3 years was 10% (95% CI = 5%-19%). CONCLUSIONS: Given the modest rate of motor deterioration over three years, watchful waiting may be a reasonable management approach in 12- to 35-month-old children with IXT. To confirm this recommendation would require a long-term randomised trial of immediate treatment versus observation followed by deferred treatment if needed.

A Randomized Trial Comparing Bilateral Lateral Rectus Recession versus Unilateral Recess and Resect for Basic-Type Intermittent Exotropia.

PURPOSE: To compare long-term outcomes after bilateral lateral rectus recession (BLRc) or unilateral lateral rectus recession combined with medial rectus resection in the same eye (R&R) for primary treatment of childhood intermittent exotropia (IXT). DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS: One hundred ninety-seven children 3 to younger than 11 years of age with basic-type IXT, a largest deviation by prism and alternate cover test at any distance of 15 to 40 prism diopters (PD), and near stereoacuity of at least 400 seconds of arc. METHODS: Random assignment to BLRc or R&R and masked examinations conducted every 6 months after surgery for 3 years. MAIN OUTCOME MEASURES: Proportion of participants meeting suboptimal surgical outcome by 3 years, defined as: (1) exotropia of 10 PD or more at distance or near using simultaneous prism and cover test (SPCT); or (2) constant esotropia of 6 PD or more at distance or near using SPCT; (3) loss of 2 octaves or more of stereoacuity from baseline, at any masked examination; or (4) reoperation without meeting any of these criteria. RESULTS: Cumulative probability of suboptimal surgical outcome by 3 years was 46% (43/101) in the BLRc group versus 37% (33/96) in the R&R group (treatment group difference of BLRc minus R&R, 9%; 95% confidence interval [CI], -6% to 23%). Reoperation by 3 years occurred in 9 participants (10%) in the BLRc group (8 of 9 met suboptimal surgical outcome criteria) and in 4 participants (5%) in the R&R group (3 of 4 met suboptimal surgical outcome criteria; treatment group difference of BLRc minus R&R, 5%; 95% CI, -2% to 13%). Among participants completing the 3-year visit, 29% (25 of 86) in the BLRc group and 17% (13 of 77) in the R&R group underwent reoperation or met suboptimal surgical outcome criteria at 3 years (treatment group difference of BLRc minus R&R, 12%; 95% CI, -1% to 25%). CONCLUSIONS: We did not find a statistically significant difference in suboptimal surgical outcome by 3 years between children with IXT treated with BLRc compared with those treated with R&R. Based on these findings, we are unable to recommend one surgical approach over the other for childhood IXT.

Evaluation of structural contributors in myopic eyes of preterm and full-term children.

PURPOSE: We conducted a cross-sectional study to test the hypothesis that the structural contributions to myopia in preterm and full-term born children are different. METHODS: In this study, 93 children ranging from ages 2 to 13 who had myopia ≥ -3 diopters in at least one eye were examined with A-scans. The following data was collected and analyzed: history of birth, refractive error (RE), cornea thickness (CT) and average corneal curvature (AVK), depth of anterior chamber (ACD), lens thickness (LT), and axial length (AL) of the eye. RESULTS: Eyes were tested and categorized into four groups: myopic eyes in full-term children (group 1), myopic eyes in premature children (group 2), non-myopic eyes in full-term children (group 3), and non-myopic eyes in preterm children (group 4). The RE were similar between group 1 and group2, and between group 3 and group 4. Myopic eyes in group 2 had higher AVK as compared to group 3; 45.4 ± 0.4 D vs. 43.5 ± 0.7 D, p = 0.008. The ACD in group 2 was shallower than that in group 1 (2.5 ± 0.5 vs. 3.2 ± 0.3, p = 0.01). The LT measurements in group 2 were thicker than those in group 1 (mean LT = 4.9 ± 1.0 vs 4.1 ± 0.3 mm, p = 0.001, respectively). Finally, AL of myopic eyes in group 1 was longer than that of group 2, p = 0.01. CONCLUSION: These results suggest that increased axial length plays an important role in myopia in full-term children, whereas corneal curvature and lens thickness are major contributors to myopia in preterm children.

Strabismus Surgery in Hemophilia: A Novel Surgical Technique and Guideline Recommendations.

Hemophilia is a serious X-linked inheritance coagulation factor deficiency. Clinically, prolonged bleeding or delayed clotting in any area of vascular disturbance is the main manifestation of all hemophilia. We presented a 23-year-old male with a history of left sensory esotropia since the age of three. The patient had not undergone any previous eye surgery and refused to wear glasses. Hematologic studies confirmed a diagnosis of hemophilia A. Upon ophthalmologic examination, the patient's visual acuity was 20/20 in the right eye and 20/120 in the left eye, with deep amblyopia. The patient exhibited left inferior oblique overaction and a V pattern. The ophthalmologic examination otherwise revealed no abnormalities. Preoperative correction of factor VIII was deemed necessary, and the recommended dose was administered to raise the factor VIII level to 52%. The patient underwent bilateral medial rectus recession, left lateral rectus plication, and left inferior oblique myectomy. A new technique utilizing viscodissection with subconjunctival injection of a viscoelastic solution was employed to minimize intraoperative bleeding, resulting in reduced bleeding compared to standard strabismus surgery. No unusual bleeding occurred during the procedure. No postoperative bleeding was observed. The patient was discharged on the fourth postoperative day, having achieved satisfactory cosmetic alignment in the primary position with no complications related to hemophilia. In conclusion, strabismus surgery can be performed safely in strabismic patients with hemophilia. Viscodissection is a helpful novel surgical technique to decrease the risk of bleeding during surgery, and we recommend using this technique in patients using anticoagulants. A multidisciplinary team approach and strict post-operative monitoring are essential in order to achieve optimal results.

IMI-Management and Investigation of High Myopia in Infants and Young Children.

Purpose: The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤-6 diopters [D]) in infants and young children. Findings: High myopia is rare in pre-school children with a prevalence less than 1%. The etiology of myopia in such children is different than in older children, with a high rate of secondary myopia associated with prematurity or genetic causes. The priority following the diagnosis of high myopia in childhood is to determine whether there is an associated medical diagnosis that may be of greater overall importance to the health of the child through a clinical evaluation that targets the commonest features associated with syndromic forms of myopia. Biometric evaluation (including axial length and corneal curvature) is important to distinguishing axial myopia from refractive myopia associated with abnormal development of the anterior segment. Additional investigation includes ocular imaging, electrophysiological tests, genetic testing, and involvement of pediatricians and clinical geneticists is often warranted. Following investigation, optical correction is essential, but this may be more challenging and complex than in older children. Application of myopia control interventions in this group of children requires a case-by-case approach due to the lack of evidence of efficacy and clinical heterogeneity of high myopia in young children. Conclusions: High myopia in infants and young children is a rare condition with a different pattern of etiology to that seen in older children. The clinical management of such children, in terms of investigation, optical correction, and use of myopia control treatments, is a complex and often multidisciplinary process.

Developmental Improvement in Children With Intellectual Disability After Photorefractive Keratectomy for Severe Isoametropia.

PURPOSE: To assess the impact of refractive error correction from photorefractive keratectomy on development in children with severe isoametropia, subnormal visual acuity, and intellectual disability unable to use refraction correction. DESIGN: Prospective noncomparative interventional case series. METHODS: Before and after photorefractive keratometry (PRK), subjects who had plateaued developmentally for 18 or more months were assessed using a battery of developmental tests. The primary outcome measure was the change in the developmental quotient (DQ) 6 months after PRK. Secondary outcomes were the change in the DQ, uncorrected visual acuity, cycloplegic refraction, and corneal status 12, 24, and 36 months after PRK. RESULTS: Sixteen subjects aged 2 to 8 years were included. Twelve were highly myopic (mean, -9.69 ± 3.82 diopters [D]), 3 highly hyperopic (mean, +5.75 ± 0.59 D) and 1 highly astigmatic (mean, +3.50 D). Six months after PRK, the DQ significantly improved for expressive communication (mean, 4.51 ± 2.27 months; P = .04), interpersonal relationships (mean, 9.45 ± 4.18 months; P = .02) and coping (mean, 6.44 ± 2.10 months; P = .05). Twelve months after PRK, the DQ significantly improved for receptive communication (8.04 ± 1.80 months; P < .001), expressive communication (6.99 ± 2.27 months; P < .05), written communication (9.28 ± 3.72 months; P < .04), domestic skills (6.50 ± 2.43 months; P < .03), interpersonal relationships (10.57 ± 4.17 months; P < .02), and coping (8.41 ± 3.25 months; P < .5). CONCLUSIONS: PRK significantly improves developmental abilities of children with intellectual disability, severe isoametropia, and previously plateaued development, in addition to improving visual acuity and refractive error.

Severe congenital chorioretinitis caused by congenital lymphocytic choriomeningitis virus infection.

PURPOSE: To describe a case of congenital lymphocytic choriomeningitis virus (LCMV), a potentially severe and under-diagnosed etiology of congenital chorioretinitis. OBSERVATIONS: A 5-month old boy presented with esotropia. Examination revealed light perception vision in the right eye and normal fixation and following behavior in the left eye, and a 50PD esotropia with full versions. The external, anterior segment, and pupil exams were normal. Fundus examination demonstrated slightly pale optic nerves, numerous geographic atrophic and hyperpigmented lesions along the vascular arcades in both eyes that extended into the fovea of the right eye. Head computed tomography (CT) imaging demonstrated bilateral cerebral volume loss with consequential ex vacuo dilation of the lateral ventricles and scattered intracranial calcifications. Serum IgG and IgM titers for toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), syphilis, and zika were all negative. Upon communication of negative TORCHS titers, the mother recalled a severe rat infestation of their home during the pregnancy. A LCMV antibody titer was then ordered and which resulted positive for IgG antibodies. CONCLUSIONS AND IMPORTANCE: Congenital LCMV infection is an under-recognized cause of congenital chorioretinitis.

Novel finding of atrophic extraocular muscles in Loeys-Dietz syndrome: a case report and review of the literature.

A 19-year-old man with Loeys-Dietz syndrome and right exotropic Duane syndrome after bilateral lateral rectus recessions at age 22 months presented with recurrent progressive exotropia 17 years after his initial surgery. Surgical correction was aborted intraoperatively when extreme atrophy of the right medial rectus, lateral rectus, and superior rectus muscles was observed, later corroborated by orbital magnetic resonance imaging.

Persistent epithelial defect after photorefractive keratectomy in a patient with autism.

Refractive surgery has been performed under general anesthesia on pediatric and neurobehaviorally challenged adults without reported loss of vision or serious complications. Persistent epithelial defect (PED) is a rare complication of photorefractive keratectomy (PRK) in the general refractive surgery population. We report a case of PED following PRK under general anesthesia for high myopia in a man with autism and ocular history of juvenile open-angle glaucoma and dry eye syndrome.

Prospective Longitudinal Evaluation of the Peripheral Choroidal Thickness in High-Risk Infants with Retinopathy of Prematurity: A Pilot Study.

OBJECTIVE: The purpose of this study was to prospectively follow up the peripheral choroidal development and thickness for retinopathy of prematurity (ROP) in high-risk premature infants using optic coherence tomography. MATERIALS AND METHODS: All infants included in the analysis had an optical coherence tomography (OCT) evaluation, serially over 6 weeks, starting at the first ROP screening exam and at each follow-up screening exam. We included infants born at or earlier than 25 weeks of gestation, weighing less than 700 grams, and those who developed interventricular hemorrhage. We evaluated the choroidal thickness and development, centrally and at the extreme nasal and temporal periphery, for each eye with each ROP screening exam. Changes in the choroidal thickness and the choroidal thickness to retinal thickness ratio (C/R ratio) were evaluated over time not only for each individual infant, but between the infants as well. RESULTS: Six infants met our inclusion criteria. Infants with severe ROP had a mean choroidal thickness that was significantly thinner in the extreme temporal periphery than infants that did not develop significant ROP (P=0.02). The mean value of the C/R ratio was smaller in infants with severe ROP compared to those that did not develop any significant ROP at any of the evaluated locations (P < 0.001). CONCLUSION: The peripheral choroid appears to be significantly thinner relative to the retinal thickness in infants with severe ROP.

Corneal indices following photorefractive keratectomy in children at least 5 years after surgery.

PURPOSE: To evaluate long-term corneal outcomes in pediatric patients who underwent photorefractive keratotomy (PRK) for the treatment of refractive amblyopia. METHODS: In this prospective interventional case series, children with refractive amblyopia underwent PRK between January 1, 2007, and December 31, 2011, at Texas Children's Hospital's Department of Ophthalmology, a single tertiary eye center, and were followed for at least 5 years after surgery. Main outcome measures were 5+ years postoperative indices of corneal thickness, keratometry, degree of corneal haze, and presence or absence of keratectasia. RESULTS: Twelve eyes of 8 subjects aged 3-9 years who underwent PRK and were followed for at least 5 years were included. The mean PRK treatment dose was 8.46 D for the myopic cohort and 4.49 D for the hyperopic cohort, which removed an average of 72 µm of corneal stromal tissue in addition to the 50 µm of corneal epithelium that was removed prior to laser ablation. The mean corneal thickness was 563 µm preoperatively, which decreased to 441 µm immediately following the PRK. The mean corneal thickness 5+ years after PRK was stable, at 498 µm, because of epithelial regrowth. None of the subjects developed visually significant corneal haze or topographic evidence of keratectasia. CONCLUSIONS: In this study cohort, there were no topographic signs of keratectasia or corneal haze in children treated with PRK for high refractive error 5 years or more after surgery.

Cortical Visual Impairment in Congenital Cytomegalovirus Infection.

PURPOSE: To describe the presentation, evolution, and long-term outcome of cortical visual impairment (CVI) in patients with symptomatic congenital cytomegalovirus (CMV) infection, and to identify risk factors for the development of CVI in patients with symptomatic congenital CMV. METHODS: Retrospective subanalysis of a long-term prospective cohort study with data gathered from 1982 to 2013. RESULTS: Eleven of 77 (14.3%) patients with symptomatic CMV, 0 of 109 with asymptomatic CMV, and 51 control patients had CVI. Overall, patients with symptomatic CMV had worse vision than patients with asymptomatic CMV, who in turn had worse vision than control patients. Microcephaly, intracranial calcification, dilatation of ventricles, encephalomalacia, seizure at birth, optic atrophy, chorioretinitis/retinal scars, strabismus, and neonatal onset of sensorineural hearing loss were risk factors associated with CVI. CONCLUSIONS: CVI may result from symptomatic congenital CMV infection. The relationship of CVI and its risk factors in patients with CMV suggests the potential to predict the development of CVI through predictive modeling in future research. Early screening of CVI in children born with symptomatic congenital CMV can facilitate educational, social, and developmental interventions. [J Pediatr Ophthalmol Strabismus. 2019;56(3):194-202.].

Instability of ocular alignment in childhood esotropia.

OBJECTIVE: Instability of ocular alignment may cause surgeons to delay surgical correction of childhood esotropia. The authors investigated the stability of ocular alignment over 18 weeks in children with infantile esotropia (IET), acquired nonaccommodative esotropia (ANAET), or acquired partially accommodative esotropia (APAET). DESIGN: Prospective, observational study. PARTICIPANTS: Two hundred thirty-three children aged 2 months to less than 5 years with IET, ANAET, or APAET of less than 6 months' duration. METHODS: Ocular alignment was measured at baseline and at 6-week intervals for 18 weeks. MAIN OUTCOME MEASURES: Using definitions derived from a nested test-retest study and computer simulation modeling, ocular alignment was classified as unstable if there was a change of 15 prism diopters (PD) or more between any 2 of the 4 measurements, as stable if all 4 measurements were within 5 PD or less of one another, or as uncertain if neither criteria was met. RESULTS: Of those who completed all 3 follow-up visits within time windows for analysis, 27 (46%) of 59 subjects with IET had ocular alignment classified as unstable (95% confidence interval [CI], 33%-59%), 20% as stable (95% CI, 11%-33%), and 34% as uncertain (95% CI, 22%-47%). Thirteen (22%) of 60 subjects with ANAET had ocular alignment classified as unstable (95% CI, 12%-34%), 37% as stable (95% CI, 25%-50%), and 42% as uncertain (95% CI, 29%-55%). Six (15%) of 41 subjects with APAET had ocular alignment classified as unstable (95% CI, 6%-29%), 39% as stable (95% CI, 24%-56%), and 46% as uncertain (95% CI, 31%-63%). For IET, subjects who were older at presentation were less likely to have unstable angles than subjects who were younger at presentation (risk ratio for unstable vs stable per additional month of age, 0.85; 99% CI, 0.74-0.99). CONCLUSIONS: Ocular alignment instability is common in children with IET, ANAET, and APAET. The impact of this finding on the optimal timing for strabismus surgery in childhood esotropia awaits further study. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Heart rate variability changes and its association with the development of severe retinopathy of prematurity.

PURPOSE: To evaluate differences in autonomic nervous system (ANS) activity associated with the development of retinopathy of prematurity. METHODS: Heart rate variability (HRV) as an indicator of ANS activity was calculated in two groups of premature infants: (1) a treatment group of infants who developed type 1 ROP and underwent treatment and (2) a control group of infants who did not develop ROP more severe than stage 1 and who were matched to the treatment group in terms of age, weight, and similar risk factors, including similar frequency of intraventricular hemorrhage, bronchopulmonary dysplasia, and sepsis. HRV was analyzed during the first 5 days of life, within 5 days of initial ROP examination, and within 5 days of ROP treatment for the treatment group or, for controls, on the day of last electrocardiogram data prior to discharge. Calculations were performed for the high frequency, low frequency, and low frequency-high frequency values of the HRV components for all infants. RESULTS: Between the initial ophthalmologic evaluation and the final evaluation, there was a tendency for reduction in both the low- and high-frequency components of the HRV indices in the treatment group, whereas there was a tendency for an increase in both components of the HRV indices in the control group. The difference in the rate of change of the high frequency between groups was statistically significant (P = 0.021). CONCLUSIONS: Disruption in ANS activity may play an important role in the development and severity of ROP.

Effects of foveal ablation on emmetropization and form-deprivation myopia.

PURPOSE: Because of the prominence of central vision in primates, it has generally been assumed that signals from the fovea dominate refractive development. To test this assumption, the authors determined whether an intact fovea was essential for either normal emmetropization or the vision-induced myopic errors produced by form deprivation. METHODS: In 13 rhesus monkeys at 3 weeks of age, the fovea and most of the perifovea in one eye were ablated by laser photocoagulation. Five of these animals were subsequently allowed unrestricted vision. For the other eight monkeys with foveal ablations, a diffuser lens was secured in front of the treated eyes to produce form deprivation. Refractive development was assessed along the pupillary axis by retinoscopy, keratometry, and A-scan ultrasonography. Control data were obtained from 21 normal monkeys and three infants reared with plano lenses in front of both eyes. RESULTS: Foveal ablations had no apparent effect on emmetropization. Refractive errors for both eyes of the treated infants allowed unrestricted vision were within the control range throughout the observation period, and there were no systematic interocular differences in refractive error or axial length. In addition, foveal ablation did not prevent form deprivation myopia; six of the eight infants that experienced monocular form deprivation developed myopic axial anisometropias outside the control range. CONCLUSIONS: Visual signals from the fovea are not essential for normal refractive development or the vision-induced alterations in ocular growth produced by form deprivation. Conversely, the peripheral retina, in isolation, can regulate emmetropizing responses and produce anomalous refractive errors in response to abnormal visual experience. These results indicate that peripheral vision should be considered when assessing the effects of visual experience on refractive development.

Ultrasound biomicroscopy (UBM) characteristics of scleral tunnels created with suture needles commonly used during strabismus surgery.

PURPOSE: To enhance the safety and efficacy of surgical treatment of strabismus, we sought to measure and determine the ultrasound biomicroscopy (UBM) profile of scleral tunnels created with needles commonly used during strabismus surgery, to determine which needles are less likely to create the complication of scleral perforation. METHODS: Adult cadaver eyes were secured in a styrofoam head. Intraocular pressure was maintained between 15 and 21 mm Hg. Then S14, S24, S28 and TG100 needles were used to create scleral tunnels simulating those created during routine strabismus surgery. Ten scleral tunnels were created with each needle type at 3 different sites on the globe, for a total of 120 passes. The thickness of the sclera and the maximum depth and length of each scleral tunnel were measured using UBM. RESULTS: The mean tunnel depth below the scleral surface (+/- SD) was 0.43 +/-0.11 mm, 0.37 +/-0.09, 0.40 +/-0.08 and 0.34 +/-0.07 mm, for the S14, S24, S28 and TG100 needles, respectively (P=0.002, One way ANOVA). For both the S14 and S28 needles, there was a "statistically significant" P 0.05) linear trend of an increase in the depth of the pass as the length of the pass increased (P=0.01 for the S14 and P=0.02 for the S28 {Pearson Correlation 2 tailed test}). A similar trend was found with the S24 needle but the trend was not "statistically significant" (P=0.35). No such trend was found with the TG100 needle. CONCLUSIONS: Needle design had a definite impact on the characteristics of scleral tunnels created to simulate those made during strabismus surgery and may influence needle selection by the surgeon for different or various surgical circumstances, but the differences were not such as to predicate for or against the general use of any of these four needles for strabismus surgery.

Long-term Visual and Ocular Sequelae in Patients With Congenital Cytomegalovirus Infection.

BACKGROUND: Cytomegalovirus (CMV) is the most common congenital viral infection in the United States. Visual and ocular sequelae in adolescents and adults who are congenitally infected with CMV have not been well studied. Better understanding of the long-term visual and ocular sequelae can help with early detection, intervention and appropriate educational accommodations. METHODS: This study evaluated 237 patients (77 symptomatic, 109 asymptomatic and 51 control) who underwent a series of age-appropriate ophthalmologic, audiologic and neurodevelopmental examinations from 1982 to 2013. The frequency and etiology of visual impairment and other nonophthalmologic findings were recorded for each patient. Ophthalmologic findings were tabulated, and risk factors for abnormalities were analyzed. RESULTS: Fourteen of the 77 (18.2%) symptomatic and none of the asymptomatic and control subjects had severe visual impairments (P ≤ 0.006). Moderate visual impairment did not differ between symptomatic and asymptomatic subjects. Three asymptomatic subjects had retinal scars. The most common visual or ocular sequelae in the symptomatic group were strabismus (23.4%), chorioretinal scars (19.5%), cortical visual impairment (14.3%), nystagmus (14.3%) and optic nerve atrophy (11.7%). Three symptomatic patients had delayed visual deterioration because of later occurring retinal disorders: peripheral retinal scar, rhegmatogenous retinal detachment and Coats' disease. CONCLUSION: Symptomatic CMV patients experienced more ophthalmologic sequelae and significantly worse visual outcomes than asymptomatic CMV and control patients. Later occurring retinal disorders were found in symptomatic patients, and there is no clear evidence that CMV can reactivate in the retinas of children who were congenitally infected. Major risk factors for severe visual impairment included symptomatic status, optic nerve atrophy, chorioretinitis, cortical visual impairment and sensorineural hearing loss.

An exome sequencing study of Moebius syndrome including atypical cases reveals an individual with CFEOM3A and a TUBB3 mutation.

Moebius syndrome is characterized by congenital unilateral or bilateral facial and abducens nerve palsies (sixth and seventh cranial nerves) causing facial weakness, feeding difficulties, and restricted ocular movements. Abnormalities of the chest wall such as Poland anomaly and variable limb defects are frequently associated with this syndrome. Most cases are isolated; however, rare families with autosomal dominant transmission with incomplete penetrance and variable expressivity have been described. The genetic basis of this condition remains unknown. In a cohort study of nine individuals suspected to have Moebius syndrome (six typical, three atypical), we performed whole-exome sequencing to try to identify a commonly mutated gene. Although no such gene was identified and we did not find mutations in PLXND1 and REV3L, we found a de novo heterozygous mutation, p.E410K, in the gene encoding tubulin beta 3 class III (TUBB3), in an individual with atypical Moebius syndrome. This individual was diagnosed with near-complete ophthalmoplegia, agenesis of the corpus callosum, and absence of the septum pellucidum. No substantial limb abnormalities were noted. Mutations in TUBB3 have been associated with complex cortical dysplasia and other brain malformations and congenital fibrosis of extraocular muscles type 3A (CFEOM3A). Our report highlights the overlap of genetic etiology and clinical differences between CFEOM and Moebius syndrome and describes our approach to identifying candidate genes for typical and atypical Moebius syndrome.