Orbital leiomyoma presenting as inverse globe retraction syndrome: a unique presentation of a rare disease.

Inverse globe retraction syndrome is a rare ocular motility disorder characterized by limited abduction, with globe retraction and up- or downshoots on attempted abduction, differentiating it from globe retraction due to Duane retraction syndrome, seen on attempted adduction. It can be congenital or acquired. We report the case of a 3-year-old girl who presented with classical features of inverse globe retraction syndrome secondary to an underlying orbital tumor involving the medial rectus muscle. Incisional biopsy confirmed the diagnosis of a leiomyoma. At 10 months' follow-up, vision, ocular alignment, and ocular motility had improved.

Clinical characteristics and surgical approach in Duane retraction syndrome: a study of 691 patients.

PURPOSE: To evaluate the clinical findings of different types of Duane retraction syndrome (DRS). STUDY DESIGN: Retrospective. METHODS: This study was performed on 691 patients with DRS who underwent surgery. Clinical examinations included laterality, abnormal head posture (AHP), corrected distance visual acuity (CDVA), refractive error, amblyopia, deviation, overshoots, and type of surgery. RESULTS: The mean age of patients with DRS was 16.7 ± 12.5 (range 1.0-73) years. The patients included 396 (57.3%) women and 295 (42.7%) men (P < 0.001). DRS type I, was observed in 429 (62.1%), II in 168 (24.3%), III in 88 (12.7%) and IV in 6 (0.9%) patients. Unilateral DRS was observed OS in 628 (90.9%) [471 (%78.9) and OD in 157 (21.1%) eyes (P < 0.001)]. O ther clinical findings were AHP (n = 522, 78.1%), overshoot (n = 236, 34.2%) and amblyopia (n = 118, 17.1%). The prevalence of overshoot in types I, II, and III was 17.5% (75/429), 60.7% (102/168) and 64.8% (57/88), respectively (P < 0.001). The prevalence of amblyopia was significantly lower in patients with AHP (80/522, 15.3%) compared to patients with normal head posture (38/169, 22.5%) (P = 0.023). The mean angle of deviation in the primary position (PP) at distance was 21.7 ± 11.5 △ for esotropic group and 17.8 ± 12.4 △ for exotropic group. Sixty-two (9.0%) patients required second surgery for resolving residual misalignment (1.1 surgeries for each patient). CONCLUSIONS: About two-thirds of DRS patients had AHP, one-third had overshoots, and one-sixth had amblyopia. The results show that different types of DRS are associated with different epidemiological and clinical characteristics.

Expanding the Phenotype of the FAM149B1-Related Ciliopathy and Identification of Three Neurogenetic Disorders in a Single Family.

Biallelic truncating FAM149B1 variants result in cilia dysfunction and have been reported in four infants with Joubert syndrome and orofaciodigital syndrome type VI, respectively. We report here on three adult siblings, 18 to 40 years of age, homozygous for the known FAM149B1 c.354_357delinsCACTC (p.Gln118Hisfs*20) variant. Detailed clinical examinations were performed including ocular and gait analyses, skeletal- and neuroimaging. All three patients presented with neurological and oculomotor symptoms since birth and mild skeletal dysplasia in infancy resulting in characteristic gait abnormalities. We document mild skeletal dysplasia, abnormal gait with increased hip rotation and increased external foot rotation, ataxia, variable polydactyly, ocular Duane syndrome, progressive ophthalmoplegia, nystagmus, situs inversus of the retinal vessels, olfactory bulb aplasia, and corpus callosal dysgenesis as novel features in FAM149B1-ciliopathy. We show that intellectual disability is mild to moderate and retinal, renal and liver function is normal in these affected adults. Our study thus expands the FAM149B1-related Joubert syndrome to a mainly neurological and skeletal ciliopathy phenotype with predominant oculomotor dysfunction but otherwise stable outcome in adults. Diagnosis of FAM149B1-related disorder was impeded by segregation of multiple neurogenetic disorders in the same family, highlighting the importance of extended clinical and genetic studies in families with complex phenotypes.

Variant types of Duane retraction syndrome: synergistic divergences and convergences.

PURPOSE: To present the clinical features of 4 patients with Duane retraction syndrome characterized by synergistic divergence or convergence, abnormal vertical movements, and accessory fibrotic bands. METHODS: The medical records of 4 patients were reviewed retrospectively for the following clinical manifestations: visual acuity, refraction, ocular alignments, ocular motility, head position, magnetic resonance imaging, surgical techniques, and outcomes. RESULTS: All 4 cases were diagnosed as variants of Duane retraction syndrome. Two cases (cases 1 and 2) had synergistic divergence with unilateral adduction deficit, and 2 (cases 3 and 4) had synergistic convergence with bilateral abduction deficit. Case 2 manifested abnormal vertical movements of the right eye, which goes down with adduction of the left eye and goes up oppositely with abduction of left eye. Accessory fibrotic bands were detected beside the medial rectus muscle of both eyes in case 3. Synergistic convergence in case 4 occurred only after the first strabismus surgery. Weakening of the misinnervated horizontal rectus muscle improved ocular alignment and head position in cases 1, 3, and 4. CONCLUSIONS: Synergistic divergence and convergence are extremely rare and may present with a great diversity of clinical features. A good outcome is very difficult to achieve; however, weakening of the misinnervated horizontal rectus muscle was therapeutic in these patients.

Effect of lateral rectus muscle resection on abduction in Duane retraction syndrome type 1.

PURPOSE: To assess the effect of lateral rectus muscle resection on abduction in Duane retraction syndrome (DRS) type 1. METHODS: The medical records of patients with DRS type 1 were reviewed retrospectively. Fifteen patients who underwent lateral rectus resection were included. Prism and cover test and the Krimsky test were used to detect deviations. Ocular ductions, abnormal head position (AHP), and globe retraction were recorded. RESULTS: Nine (60.0%) patients were female. The mean age was 13.1 ± 2.3 (range, 2-34) years. Left eyes were included in ten (66.7%) patients. Mean follow-up time was 37.6 ± 16.6 (range, 6-70) months. All patients had AHP, 13 patients had mild globe retraction, and 2 patients had no globe retraction preoperatively. Mean lateral rectus resection was 3.1 ± 0.7 (range, 2.0-4.5) mm, and the mean medial rectus recession was 4.4 ± 0.6 (range, 3.0-5.0) mm. The mean preoperative deviation decreased from 23.3 ± 6.9 (range, 14-35) prism diopters (pd) to 2.2 ± 4.1 (range, 0-10) pd at near, and from 23.6 ± 7.1 (range, 14-35) pd to 1.8 ± 3.5 (range, 0-10) pd at distance, at 6 months postoperatively (p = 0.01). The mean limitation in abduction decreased from - 3.2 ± 0.9 to - 1.3 ± 1.1 postoperatively (p < 0.001). AHP resolved in all patients. There was not a limitation in adduction or a worsening of globe retraction in any patient. CONCLUSION: Lateral rectus resection can be used to improve abduction in patients with DRS type 1 who have mild globe retraction. We assume that this procedure has no worsening effect on globe retraction in appropriate cases.

Síndrome de Pierre Robin associada à Síndrome de Duane familiar do tipo III / Pierre Robin Syndrome associated with type III familial Duane Retraction Syndrome

Resumo A síndrome de Pierre Robin (PRS) consiste em uma tríade de anomalias caracterizada por micrognatia, glossoptose e fissura de palato, comumente associada com outras síndromes e ocasionalmente com alterações oculares. Na Síndrome de Duane (DRS), há uma falha na inervação do reto lateral pelo VI nervo, com inervação anômala do reto lateral por fibras do III nervo. Ainda que a PRS já tenha sido associada com mais de 50 outras síndromes, não existe na literatura relato de casos de associação com a DRS familiar. Dessa forma, esse trabalho tem por objetivo relatar um caso dessa associação em um paciente de 29 anos com recorrência das síndromes na família.

Abstract The Pierre Robin Syndrome (PRS) consists of a triad of anomalies characterized by micrognathia, glossoptosis and fissure of the palate, usually associated with other syndromes e occasionally associated with ocular variations. In Duane Retraction Syndrome (DRS), there is a failure in the lateral rectus innervation by the VI cranial nerve, with anomalous innervation of the lateral rectus by fibers of the III nerve. Even though PRS has already been associated with more than 50 other syndromes, there is not any report in literature of association with familial DRS. Thus, this work aims to report a case of this association in a 29 years old patient with recurrence of the syndromes in the family.

Síndrome de Duane tipo II con upshoot marcado / Duane's syndrome type II with marked upshoot

El síndrome de Duane es una alteración de la motilidad ocular caracterizada por la retracción del globo ocular y el estrechamiento de la hendidura palpebral con la aducción, asociada a la restricción de la abducción, aducción o ambas. Han surgido muchas teorías sobre la etiología del síndrome de Duane, pero la mayoría de los autores coinciden en que es consecuencia de una alteración congénita del VI par craneal, con una inervación aberrante del recto lateral por el III par craneal. Esta es la causa más frecuente de inervación aberrante ocular congénita. Es más frecuente en el ojo izquierdo. El síndrome de Duane tipo I es el más frecuente, y es menos frecuente el tipo II. Presentamos dos pacientes masculinos de 11 y 37 años de edad respectivamente, con diagnóstico de síndrome de Duane tipo II, con exotropía de 15 grados por Hirchsberg en el ojo izquierdo y en el ojo derecho respectivamente; tortícolis mentón a la derecha, limitación de la aducción con estrechamiento de la hendiduda palpebral y marcado upshoot en relación con el ojo afecto. Se decide realizar reseción del recto lateral 8,0 mm del ojo afectado más Y split, para mejorar el marcado upshoot. Los pacientes después de la cirugía estaban en ortotropía sin upshoot, ni tortícolis(AU)

Duane's syndrome is an eye motility disorder characterized by globe retraction and palpebral fissure narrowing with adduction, associated to abduction restriction, adduction restriction or both. Many theories have been put forth about the etiology of Duane's syndrome, but most authors agree that it is the consequence of a congenital alteration of the sixth cranial pair with aberrant innervation of the lateral rectus by the third cranial pair. This is the most common cause of congenital aberrant ocular innervation, and is more frequent in the left eye. Duane's syndrome type I is the most common and type II is the least common. A presentation is provided of two male patients aged 11 and 37 years with a diagnosis of Duane's syndrome type II with 15 degree exotropia on Hirchsberg's scale in the left and right eye, respectively, chin torticollis to the right, adduction limitation with palpebral fissure narrowing, and marked upshoot in relation to the affected eye. It is decided to perform resection of the lateral rectus 8.0 mm from the affected eye plus Y split to improve the marked upshoot. After surgery the patients were on orthotropics without upshoot or torticollis(AU)

Anomalous Vertical Deviations in Attempted Abduction Occur in the Majority of Patients With Esotropic Duane Syndrome.

PURPOSE: To describe a phenomenon, depression in attempted abduction, not previously recognized as a feature of Duane syndrome (DS). DESIGN: Retrospective, observational case series. METHODS: Setting: Institutional practice. PATIENT POPULATION: Patients diagnosed with esotropic DS at Boston Children's Hospital from 2002 to 2015. Patients with clinical photographs documenting horizontal gaze were included. Patients with prior strabismus surgery were excluded. OBSERVATION PROCEDURES: Patients were classified into 3 groups according to their vertical eye position in attempted abduction: midline group, depression group, and elevation group. Group assignment was performed by 3 independent ophthalmologists. Baseline characteristics, eye movement, and ocular deviation were compared among the 3 groups. MAIN OUTCOME MEASURES: Horizontal and vertical deviation on attempted abduction in the DS eye. RESULTS: Depression in attempted abduction was present in 74 of 113 unilateral patients (66%) and 18 of 42 gradable eyes (43%) of bilateral patients. Abduction limitation was significantly less severe in the midline group (median: -3.0) than in the depression group (median: -4.0) (P = .01). Vertical deviation in attempted abduction was more severe in the elevation group than in the depression group (P = .003). CONCLUSIONS: Depression of the eye in attempted abduction has not been widely described, yet it is present in the majority of DS patients. It is more likely to occur with more severe abduction limitation. This phenomenon is likely another form of dysinnervation in DS, the result either of anomalous vertical rectus muscle activation or asymmetric lateral rectus muscle innervation during attempted abduction. Awareness of vertical deviation in attempted abduction may facilitate surgical planning in affected patients.

Atypical Presentation of Giant Aneurysm in Pediatric Patient with Duane Syndrome.

BACKGROUND: Duane syndrome is a congenital eye movement disorder characterized by congenital malformation of the abducens nucleus. Thrombogenic conditions during development may lead to vascular anomalies in Duane syndrome; however, the presence of a giant aneurysm in this patient population is a rarely documented phenomenon. CASE DESCRIPTION: We reported a case of a large cerebral aneurysm in a pediatric patient with Duane syndrome and performed a review of the literature to identify other potential cases and associations. The pathophysiologic hallmarks of Duane syndrome that lead to alterations in the fetal cerebral vasculature and that may form the basis for a potential mechanism for aneurysm formation were reviewed in this study. The patient was an 11-year-old female with Duane syndrome who presented with seizures. Computed tomography and magnetic resonance imaging demonstrated a large, heterogeneously enhancing right temporal mass. Intraoperatively, the mass was revealed to be a partially thrombosed giant middle cerebral artery aneurysm. After surgery, the patient had an uneventful postoperative course without residual aneurysm presented on postoperative angiogram. No clinical or radiographic appearance of recurrent aneurysm was evident at her 6-month follow-up. CONCLUSIONS: The pathophysiology of vascular anomalies with Duane syndrome may be related to thrombogenic conditions during development leading to alterations in cerebral fetal vasculature. Strong consideration for vascular anomaly should be given when evaluating cerebral masses in patients with Duane syndrome.

Missense variant in UBA2 associated with aplasia cutis congenita, duane anomaly, hip dysplasia and other anomalies: A possible new disorder involving the SUMOylation pathway.

We report a patient with aplasia cutis congenita, Duane anomaly, hip dysplasia, and other anomalies who had a de novo missense variant in UBA2, which encodes for a protein involved in the SUMOylation pathway. It has previously been suggested that UBA2 haploinsufficiency underlies scalp defects in the 19q13.11 deletion syndrome. We propose that disturbance of the SUMOylation pathway, mediated by pathogenic variants in UBA2, is a novel mechanism for aplasia cutis congenita and other phenotypic abnormalities. © 2017 Wiley Periodicals, Inc.

Duane syndrome with prominent oculo-auricular phenomenon.

Duane syndrome is a congenital cranial dysinnervation disorder involving absent or anomalous innervation of the lateral and medial rectus muscles that is sometimes associated with other manifestations of dysinnervation. We describe a patient with right esotropic Duane syndrome with a long-standing retroauricular tugging sensation in right gaze who was noted to have prominent ipsilateral oculo-auricular phenomenon, representing either abnormal enhancement of existing innervation or an uncommon dysinnervation. After successful strabismus surgery the tugging sensation improved but the phenomenon could still be elicited.

A simple and novel grading method for retraction and overshoot in Duane retraction syndrome.

Strabismus in Duane retraction syndrome is frequently associated with significant globe retraction and overshoots. However, there is no method to objectively grade retraction and overshoot. Our purpose is to describe a novel objective grading method. This novel and simple grading method has excellent agreement. It will help standardise measurements and guide the clinician in taking the decision for surgery and predicting its outcome.

Duane retraction syndrome in a patient with Duchenne muscular dystrophy.

PURPOSE: We describe the clinical features of a boy with bilateral Duane retraction syndrome (DRS), Duchenne muscular dystrophy (DMD), and other medical problems. METHODS: The child was followed-up for five years; his chart was reviewed, including the results of a muscle biopsy and genetic testing. Multiplex ligation-dependent probe amplification (MLPA) was used to interrogate deletions/duplications in the dystrophin gene. RESULTS: The proband had bilateral DRS with otherwise normal ocular motility; he also had developmental delay, mild mental retardation, and seizures. Clinical diagnosis of DMD included progressive proximal weakness, highly elevated creatine kinase levels, and a muscle biopsy showing significant dystrophic changes including contracted, degenerative, and regenerative fibers, and negative dystrophin immunostaining. MLPA documented duplication of exons 3 and 4 of the dystrophin gene. CONCLUSIONS: This boy is the third patient to be reported with DRS and DMD, the second with bilateral DRS and the only one with other neurologic features. Mutated dystrophin is present in extraocular muscles and in the central nervous system (CNS) in DMD, leaving open the question of whether this co-occurrence is the result of the genetic muscle abnormality, CNS effects caused by dystrophin mutations, or chance.

Bilateral type III Duane syndrome: a case report.

PURPOSE: Duane syndrome (DS) belongs to a group of congenital retraction syndromes, the incidence of which varies between 2% and 4% in patients with strabismus. In most cases the damage is unilateral, but it manifests as bilateral in about 20% of cases. According to the classification of Huber, type III DS exhibits a limitation of abduction and adduction. METHODS: We report the case of a 5-year-old boy from Eastern Europe who was taken to the hospital because he was unable to move both eyes horizontally from birth and had not been previously seen by an ophthalmologist. RESULTS: The examination showed inability to abduct and adduct bilaterally, with narrowing of the palpebral fissures on attempted adduction. The patient was diagnosed with bilateral type III DS. CONCLUSIONS: Treatment is individualized on a case-by-case basis. For our patient, monitoring by way of regular checkups was chosen, with the parents rejecting surgery for now.

Duane syndrome: Clinical features and surgical management.

OBJECTIVE: To further define the clinical features of Duane syndrome and analyze the surgical outcomes in a subset of these patients. DESIGN: Retrospective chart review. PARTICIPANTS: A retrospective chart review of 75 patients with Duane syndrome was performed. METHODS: Complete ophthalmologic and orthoptic data were extracted from the patients' charts, and patients were classified into group I, II, or III based on forced primary position (PP) deviation. Eighteen patients had strabismus surgery to correct the ocular misalignment with its related abnormal head posture. RESULTS: Fifty-six percent of the cases were in group I, 16% in group II, and 28% in group III. Fifty-seven percent were female, 91% were unilateral, and 66% had left eye involvement. Ninety-six percent had fissure-narrowing/globe retraction on adduction; 67% had an upshoot, downshoot, or both; and 63% had an A, V, or X pattern. The A patterns correlated with downshoots in 100% of cases, V patterns with upshoots in 88%, and X patterns with upshoots/downshoots in 100%. In the 18 surgical candidates, there were 14 patients in group I, 4 in group II, and 0 in group III. An excellent surgical outcome occurred in 78% of patients and a fair-to-poor outcome in 22%. Upshoots/downshoots and fissure-narrowing/globe retraction patients showed modest improvement after surgery. CONCLUSIONS: There was a consistent relationship among the type of strabismus, head position, and motility defect. The type of upshoot/downshoot correlated strongly with the A, V, or X pattern. Postoperative improvements of abnormal head posture and PP alignment were achieved in the surgical subset of patients.

[Medial rectus tendon elongation with bovine pericardium for type 1 Duane's retraction syndrome]. / M.-rectus-internus-Sehnenverlängerung mit bovinem Perikard bei Duane-Retraktionssyndrom Typ 1.

BACKGROUND: Some patients with esotropic Duane's retraction syndrome (type 1) adopt a head turn to gain binocular vision. For some patients recession of the ipsilateral medial rectus muscle is not sufficient to eliminate head turn and squint angle. Surgery with tendon elongation allows the correction of larger angles and maintains a sufficient arc of contact. We report our results and experience. METHODS: We retrospectively reviewed the medical records of 10 patients with unilateral, esotropic Duane syndrome type 1 who had tendon elongation with bovine pericardium to correct a head turn or squint angle. Two patients had primary surgery with tendon elongation due to preoperative excessive angles, eight patients had tendon elongations as secondary procedures. Nine of the patients had their follow-up examination at least six weeks after surgery. RESULTS: The median preoperative angle of squint in primary position was + 27.5 pdpt, the median postoperative angle + 0 pdpt. The median dose effect relation for secondary interventions was 2.4 pdpt reduction of squint angle/mm surgery, for one patient with primary surgery and long-term follow-up 2.75 pdpt/mm. The median, preoperative head turn of seven patients with preoperative binocular functions was 20°. Postoperatively, six patients with long-term follow-up showed a median head turn of 0°. The median dose-effect relation was 3.3° reduction of head turn/mm surgery. All nine patients with long-term follow-up had a maximal head turn of 10°, six of the patients had no persisting head turn. Binocular functions were stable or better than preoperatively. CONCLUSIONS: For patients with retraction syndrome type 1, tendon elongation of the medial rectus muscle using Tutopatch® is a good option for secondary interventions or excessive preoperative squint angle or head turn.

Superior rectus transposition vs medial rectus recession for treatment of esotropic Duane syndrome.

IMPORTANCE: Superior rectus transposition (SRT) with or without medial rectus recession (MRc) has been introduced as an alternative to MRc alone for treatment of esotropic Duane syndrome; however, the effectiveness of these procedures has not been compared previously. OBJECTIVE: To compare the safety and efficacy of MRc and SRT in treatment of Duane syndrome. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of all patients with esotropic Duane syndrome who underwent surgical treatment from January 1, 2006, through December 31, 2012, in a multispecialty, hospital-based pediatric ophthalmology/adult strabismus practice at Boston Children's Hospital. Patients in the SRT group underwent SRT with or without MRc; those in the non-SRT group underwent unilateral or bilateral MRc. EXPOSURES: Surgical treatment of esotropic Duane syndrome. MAIN OUTCOMES AND MEASURES: Binocular alignment, ocular ductions, head position, stereopsis, and fundus torsion were recorded before surgery and at the 2-month and final postoperative visits. We also evaluated postoperative drift. RESULTS: The medical record review identified 36 patients who underwent 37 procedures, including 19 in the SRT group (13 SRT + MRc and 6 SRT alone) and 18 in the non-SRT group (11 unilateral MRc and 7 bilateral medial rectus resession). Mean MRc was smaller when performed with SRT (3.3 vs 5.3 mm; P = .004). Although the initial deviation was larger in the SRT group, both groups had a similar improvement in esotropia and head turn. Abduction improved by at least 1 unit in 15 of 19 patients in the SRT group (79%) vs 5 of 18 in the non-SRT group (28%). In 24 patients followed up for more than 6 months, mean esotropia decreased from 8.2 to 6.1 prism diopters (Δ) in the SRT group (n = 12) but increased from 7.2 to 10.9Δ in the non-SRT group (n = 12). CONCLUSIONS AND RELEVANCE: The combination of SRT and MRc was more effective than MRc or bilateral medial rectus resession at improving abduction while allowing for a smaller recession to align the eyes and eliminate a compensatory head posture. Although any surgery on the vertical rectus muscles should in theory increase the risk for vertical or torsional complications, to date this theory has not been borne out in our patients. Patients treated with SRT appear to have a reduced likelihood of long-term undercorrection. We therefore recommend SRT with adjustable MRc for treatment of Duane syndrome in patients with larger amounts of esotropia.

Inferior oblique myectomy for upshoots mimicking inferior oblique overaction in Duane retraction syndrome.

PURPOSE: To evaluate the results of inferior oblique myectomy in selected patients with Duane retraction syndrome with upshoot on adduction. METHODS: This was a prospective, interventional study of consecutive patients with types 1, 2, or 3 Duane syndrome with isolated upshoot in adduction operated on from January 2007 to December 2011. Patients underwent inferior oblique myectomy on the side of the upshooting eye. Only patients with gradual elevation of the eye in adduction in a pattern similar to inferior oblique overaction or patients with hypertropia in the primary position were included. All patients were followed for at least 6 months. Ductions, versions, degree of upshoot, degree of fundus torsion, and pattern of strabismus were analyzed in all patients before and after surgery. RESULTS: A total of 11 patients were included in the study. Mean patient age at time of surgery was 6.4 ± 5.2 years (range, 3-22 years). Two patients had bilateral inferior oblique myectomy and 4 had simultaneous bilateral medial rectus muscle recession to correct horizontal misalignment. Mean duration of follow-up was 8.6 months (range, 6-36 months). Of the 11 patients, 10 (91%) had complete disappearance of the upshoot at last follow-up. None of the patients developed inferior oblique underaction postoperatively. There was a statistically significant improvement of V pattern after surgery (P < 0.01). Mean vertical misalignment in primary position was 5(Δ) before surgery and 1(Δ) after (P = 0.02). Most patients had no significant fundus torsion before or after surgery. CONCLUSIONS: Inferior oblique muscle weakening can improve upshoot in selected patients with Duane retraction syndrome without inducing inferior oblique muscle underaction.

Partial chromosome 7 duplication with a phenotype mimicking the HOXA1 spectrum disorder.

PURPOSE: To evaluate possible monogenic and chromosomal anomalies in a patient with bilateral Duane retraction syndrome and hearing impairment resulting in a phenotype resembling the HOXA1 spectrum disorder. METHODS: Sequencing HOXA1 and performing high resolution array comparative genomic hybridization (arrayCGH). RESULTS: The proband had bilateral Duane retraction syndrome (DRS) with severe hearing loss bilaterally and an absent right vertebral artery, mimicking the major features of the Bosley-Salih-Alorainy variant of the HOXA1 spectrum. However, he also had developmental delay, mild mental retardation, and seizures. His parents were not related, but his father had milder sensorineural hearing loss bilaterally, and two paternal uncles and a paternal cousin had seizures. Neuroimaging revealed moderate maldevelopment of inner ear bony anatomy bilaterally. HOXA1 sequencing was normal, but arrayCGH revealed a small partial duplication of chromosome 7 encompassing only the PTPRN2 gene (protein tyrosine phosphatase, receptor type, N polypeptide 2) that was not present in his parents, an unaffected brother, or 53 normal ethnically-matched individuals. CONCLUSIONS: PTPRN2 is not yet linked to a genetic syndrome, although its expression has been identified in the adult human brain, in certain tumors, and in association with type 1 diabetes mellitus. The phenotype of this patient is strikingly similar to, but not identical to, that of the HOXA1 spectrum disorder. The findings in this patient raise the possibility that PTPRN2 may be active during early development of the human brainstem and that its overexpression may cause bilateral DRS with hearing loss as occurs in patients with homozygous HOXA1 mutations.

Duane type I retraction syndrome associated with Wyburn-Mason syndrome.

PURPOSE: Our aim is to report the co-existence of Duane's retraction syndrome and Wyburn-Mason syndrome, a rare condition characterized by arteriovenous malformations (AVMs) in the central nervous system and retina. METHODS: An 11-year-old boy was referred for evaluation of strabismus present since birth. On examination his uncorrected visual acuity was 6/6 in each eye, with small angle left eye esotropia in the primary position, ipsilateral face turn, abduction deficit, lid fissure narrowing in adduction and widening in abduction; plus typical features of left-sided type I Duane syndrome were present. The left fundus demonstrated localized, well-compensated, markedly convoluted, dilated and tortuous retinal vessels and venous congenital retinal macrovessel, which traverse the macular region. The right fundus was unremarkable. In order to elucidate if this retinal vascular malformation is associated with similar lesions in the orbit, paranasal sinuses and/or brain, magnetic resonance imaging (MRI) was performed, followed by digital subtraction angiography of the brain vessels. RESULTS: Clinical features of retinal disease (typical retinal vascular malformation) and brain imaging studies have led to the diagnosis of Wyburn-Mason syndrome. Digital subtraction angiography of the brain revealed an AVM of 30 mm maximal diameter in the left occipital lobe. CONCLUSIONS: Intracranial AVM might have affected the normal vascular development during the second month of gestation, causing involutional changes of the sixth nerve and resulted in Duane's syndrome by "steal phenomenon." Retinal AVM may point to concomitant intracranial AVMs, thus warranting neurological assessment. Patients with AVM of the retina should be examined early with brain and orbital neuroimaging to rule out cerebral AVMs.