Expanding Genotype/Phenotype Correlation in 2p11.2-p12 Microdeletion Syndrome.

Chromosomal abnormalities on the short arm of chromosome 2 in the region p11.2 have been associated with developmental delay, intellectual disability, facial anomalies, abnormal ears, skeletal and genital malformations. Here we describe a patient with a de novo interstitial heterozygous microdeletion on the short arm of chromosome 2 in the region p11.2-p12. He presents with facial dysmorphism characterized by a broad and low root of the nose and low-set protruding ears. Clinical examinations during follow-up visits revealed congenital pendular nystagmus, decreased visual acuity and psychomotor development disorder including intellectual disability. The heterozygous 5 Mb-microdeletion was characterized by an array CGH (Comparative Genomic Hybridization) analysis. In the past two decades, nine patients with microdeletions in this region have been identified by array CGH analysis and were reported in the literature. All these patients show psychomotor development disorder and outer and/or inner ear anomalies. In addition, most of the patients have mild to severe intellectual disability and show facial malformations. We reviewed the literature on PubMed and OMIM using the gene/loci names as search terms in an attempt to identify correlations between genes located within the heterozygous microdeletion and the clinical phenotype of the patient, in order to define a recognizable phenotype for the 2p11.2p12 microdeletion syndrome. We discuss additional symptoms that are not systematically present in all patients and contribute to a heterogeneous clinical presentation of this microdeletion syndrome.

Detection of Relative Afferent Pupillary Defects Using Eye Tracking and a VR Headset.

Purpose: The purpose of this study was to assess the feasibility of detecting relative afferent pupillary defects (RAPDs) using a commercial virtual reality headset equipped with an eye tracker. Methods: This is a cross-sectional study in which we compare the new computerized RAPD test with the traditional clinical standard using the swinging flashlight test. Eighty-two participants including 20 healthy volunteers aged 10 to 88 years were enrolled in this study. We present a bright/dark stimulus alternating between the eyes every 3 seconds using a virtual reality headset, and we simultaneously record changes in pupil size. To determine the presence of an RAPD, we developed an algorithm analyzing the pupil size differences. For the assessment of the performance of the automated and the manual measurement a post hoc impression based on all available data is created. The accuracy of the manual clinical evaluation and the computerized method is compared using confusion matrices and the gold standard of the post hoc impression. The latter is based on all available clinical information. Results: We found that the computerized method detected RAPD with a sensitivity of 90.2% and an accuracy of 84.4%, as compared to the post hoc impression. This was not significantly different from the clinical evaluation with a sensitivity of 89.1% and an accuracy of 88.3%. Conclusions: The presented method offers an accurate, easy to use, and fast method to measure an RAPD. In contrast to today's clinical practice, the measures are quantitative and objective. Translational Relevance: Computerized testing of Relative Afferent Pupillary Defects (RAPD) using a VR-headset and eye-tracking reaches non-inferior performance compared with senior neuro-ophthalmologists.

Accuracy and Reliability of a Handheld, Nonmydriatic Fundus Camera for the Remote Detection of Optic Disc Edema.

BACKGROUND: Optic disc edema can be an important indicator of serious neurological disease, but is poorly detected using the direct ophthalmoscope. Portable fundus photography may overcome this difficulty. INTRODUCTION: The purpose of this study was to determine the sensitivity and specificity of a handheld, nonmydriatic fundus camera for the detection of optic disc edema. MATERIALS AND METHODS: Retrospective review of nonmydriatic optic disc photographs taken with a portable fundus camera (Pictor Plus; Volk Optical, Mentor, OH) from the University of Michigan Neuro-Ophthalmology Clinics. We included 103 consecutive eyes with optic disc edema and 103 consecutive eyes without optic disc edema of 109 patients. Four masked neuro-ophthalmologists graded a single photograph of each optic disc presented in randomized order and documented the presence of optic disc edema. Sensitivity and specificity of graders' photographic interpretation was compared with clinical examinations. Reliability of assessments within and between graders was determined using kappa statistics. RESULTS: The sensitivity and specificity for detection of optic disc edema were 71.8-92.2% and 81.6-95.2%, respectively. Photos were found to be ungradable in 0-8.3% of cases. The intergrader reliabilities ranged from 0.60 [95% confidence interval (CI): 0.52-0.67] to 0.72 (95% CI: 0.66-0.77). Intragrader reliability ranged from 0.76 (95% CI: 0.63-0.92) to 0.82 (95% CI: 0.69-0.95). DISCUSSION: Photographs taken with portable, nonmydriatic technology met threshold sensitivity and specificity for remote screening for optic disc edema when performed by most, but not all graders. Reliability between graders was moderate-strong and strong within individual providers. CONCLUSIONS: Portable photography holds promise for use in remote screening of optic disc edema.

Persistent diplopia and superior oblique muscle dysfunction following dissection of the orbital periosteum in cranial base surgery.

BACKGROUND/AIMS: Persistent diplopia secondary to a fourth cranial nerve palsy is poorly documented after open cranial base surgery. METHODS: Six cases of fourth cranial nerve palsy after cranial base surgery were drawn from the Neuro-Ophthalmology and Head and Neck Surgery Clinics at the University of Michigan from 2004 to 2012. RESULTS: Six patients developed diplopia and ocular misalignment in a pattern suggestive of superior oblique palsy following dissection of the medial orbital periosteum as part of a surgical approach to the anterior cranial base. Among the four patients in whom follow-up examination was available, the misalignment improved spontaneously in three patients and was stable in the fourth patient, but did not completely resolve in any patient. CONCLUSIONS: This sparsely documented phenomenon is likely caused by dysfunction of the superior oblique muscle, possibly the result of malposition of the trochlea after spontaneous reattachment of the periosteum. Special factors such as invasive tumours, repeated surgeries of this nature, prior radiation, or chemical cementing material that adversely affects wound healing may be contributory.

Homonymous hemianopia from infarction of the optic tract and lateral geniculate nucleus in deep cerebral venous thrombosis.

A 20-year-old man developed right homonymous hemianopia, hemiparesis, and hemisensory loss from deep cerebral venous thrombosis in the setting of high altitude. Approximately 3 months later, brain MRI showed encephalomalacia of the left optic tract and lateral geniculate nucleus, as well as signal abnormalities of the internal capsule and posterolateral thalamus. Homonymous hemianopia has previously been described in 1 case after deep cerebral venous thrombosis but without detailed neuroimaging features.

A case of purtscher-like retinopathy following a motor vehicle accident.

PURPOSE: To describe a case of Purtscher-like retinopathy following seat belt compression of the chest in a motor vehicle accident. METHODS: Case report. RESULTS: A 53-year-old woman developed Purtscher-like retinopathy following compression of the chest by her seat belt in a motor vehicle accident. Observation was recommended, and on follow-up examination at 8 weeks her vision, fluorescein angiography, and optical coherence tomography had returned to baseline. CONCLUSION: Seat belts may produce chest compression to induce a Purtscher-like retinopathy in varying degrees associated with the severity of the accident and subsequent compressive forces of the seat belt.