Disease-associated polyalanine expansion mutations impair UBA6-dependent ubiquitination.

Expansion mutations in polyalanine stretches are associated with a growing number of diseases sharing a high degree of genotypic and phenotypic commonality. These similarities prompted us to query the normal function of physiological polyalanine stretches and to investigate whether a common molecular mechanism is involved in these diseases. Here, we show that UBA6, an E1 ubiquitin-activating enzyme, recognizes a polyalanine stretch within its cognate E2 ubiquitin-conjugating enzyme USE1. Aberrations in this polyalanine stretch reduce ubiquitin transfer to USE1 and, subsequently, polyubiquitination and degradation of its target, the ubiquitin ligase E6AP. Furthermore, we identify competition for the UBA6-USE1 interaction by various proteins with polyalanine expansion mutations in the disease state. The deleterious interactions of expanded polyalanine tract proteins with UBA6 in mouse primary neurons alter the levels and ubiquitination-dependent degradation of E6AP, which in turn affects the levels of the synaptic protein Arc. These effects are also observed in induced pluripotent stem cell-derived autonomic neurons from patients with polyalanine expansion mutations, where UBA6 overexpression increases neuronal resilience to cell death. Our results suggest a shared mechanism for such mutations that may contribute to the congenital malformations seen in polyalanine tract diseases.

Do-It-Yourself Low-Cost Stroboscopy.

This case series tests the construction of an extremely low-cost stroboscope and assesses its strengths and weaknesses.

Hemotympanum as a Complication of a Valsalva Maneuver during Childbirth.

Background: Hemotympanum may occur due to otic barotrauma secondary to Valsalva maneuver during the second phase of labor. A pressure differential across the tympanic membrane (TM) of about five psi can cause rupture. The increased intrathoracic and intraabdominal pressure spikes repeatedly manifested by "pushing" during second-stage labor easily approach (and may exceed) this level. Clinical Presentation. This case report describes a healthy thirty-seven-year-old multipara patient admitted for the 40-weeks' gestational age routine follow-up that proceeded to active labor followed by an aural fullness and bloody otorrhea. Otoscopic examination with a light microscope confirmed the hemotympanum of the right tympanic membrane. Conclusion: Forceful Valsalva can cause hemotympanum. Investigating the benefits and disadvantages of the pushing methods could help reduce such complications in the future. A prompt evaluation of an otolaryngologist should be requested in the event of a new postpartum hearing disturbance or bloody otorrhea.

Oculopharyngeal muscular dystrophy mutations link the RNA-binding protein HNRNPQ to autophagosome biogenesis.

Autophagy is an intracellular degradative process with an important role in cellular homeostasis. Here, we show that the RNA binding protein (RBP), heterogeneous nuclear ribonucleoprotein Q (HNRNPQ)/SYNCRIP is required to stimulate early events in autophagosome biogenesis, in particular the induction of VPS34 kinase by ULK1-mediated beclin 1 phosphorylation. The RBPs HNRNPQ and poly(A) binding protein nuclear 1 (PABPN1) form a regulatory network that controls the turnover of distinct autophagy-related (ATG) proteins. We also show that oculopharyngeal muscular dystrophy (OPMD) mutations engender a switch from autophagosome stimulation to autophagosome inhibition by impairing PABPN1 and HNRNPQ control of the level of ULK1. The overexpression of HNRNPQ in OPMD patient-derived cells rescues the defective autophagy in these cells. Our data reveal a regulatory mechanism of autophagy induction that is compromised by PABPN1 disease mutations, and may thus further contribute to their deleterious effects.

Analysis of Prognostic Factors Impacting Pediatric Acute Mastoiditis Outcomes.

BACKGROUND: This study aimed to investigate the outcomes of pediatric patients with acute mastoiditis while examining the role of intravenous steroid therapy, patient demographics, and serum inflammatory values as prognostic factors. METHODS: This study is a single-center retrospective observational study including 73 consecutive patients treated for acute mastoiditis in the course of the 10-year study period (January 2010 to December 2019). RESULTS: Data analysis showed that patients requiring surgical treatment (14%) had a 3-fold higher C-reactive protein value at admission compared to those treated conservatively (P < .001). Receiver operating characteristic analysis revealed that a C-reactive protein cut-off of ≥98.7 had a sensitivity and specificity of 100% and 74.6%, respectively, for predicting the need for surgery (area under the curve=0.927, P < .001). The duration of symptoms before hospitalization was nearly 2 days shorter in male patients (P=.031), and the use of intravenous steroid therapy significantly shortened the length of hospitalization (P=.023), by 1.4 days on average. CONCLUSION: Intravenous steroid therapy may be useful in decreasing the length of hospital stay. Mastoiditis tends to present more severely in male patients, and monitoring C-reactive protein values during treatment correlated well with the need for surgery.

Safety of a New Sinus Irrigation Device in Rhinosinusitis: A Pilot Study.

BACKGROUND: Puncture and lavage of the paranasal sinuses, previously the primary treatment for unresponsive acute bacterial rhinosinusitis before surgery, has been abandoned due to procedural discomfort and advancements in antibiotic efficacy and endoscopic surgery. The rise in antibiotic-resistant bacteria has renewed the interest in minimally invasive sinus lavage to both avoid aggressive surgical interventions and identify appropriate antibiotic therapy. In this article, we describe the safety and feasibility of a new device in human patients and evaluate its efficacy as a treatment before the traditional sinus surgery in acute rhinosinusitis. METHODS: The device with its seeker-shaped guiding tube and rotating wire can enter the sinus cavity through the natural ostium, pulverize the inspissated mucus, and enable lavage and culture sampling without the need for sinus puncturing. It was tested in 6 patients with chronic sinusitis under general anesthesia during endoscopic sinus surgery and in additional 10 patients with maxillary acute bacterial rhinosinusitis in outpatient settings under local anesthesia. RESULTS: The device enabled rapid, efficient, and atraumatic insertion of the wire into the occluded sinuses. The rotating wire permitted pulverization of the thick mucus, which enabled irrigation without mucosal damage or adverse events. Overall, 9 of 10 patients with acute bacterial rhinosinusitis demonstrated remarkable improvements and were discharged the following day with no acute symptoms. The visual analog scale score for pain dropped from 8.9 to 0.4. The remaining one patient underwent endoscopic sinus surgery subsequently. None of the patients treated during endoscopic sinus surgery developed any adverse events.

International Consensus Statement on Obstructive Sleep Apnea.

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Transillumination Assisted Cricopharyngeal Myotomy.

Abstract: Cricopharyngeal muscle myotomy (CPM) is a common intervention for relief of dysphagia in patients with Oculo-pharyngeal muscular dystrophy (OPMD). Because of difficulties in approaching and dissecting cricopharyngeal muscle in these patients, we used transillumination for the myotomy (TA-CPM). Transillumination is a simple technique to improve the guidance and navigation of the surgeon in determining the location and depth of myotomy. The purpose of this study is to evaluate the efficacy and safety of transillumination in CPM in OPMD patients. An observational cohort of patients with OPMD who underwent CPM due to dysphagia at one medical center between 2010 and 2019. Two groups of patients are included, according to whether transillumination was used during their surgery. Patients were evaluated before and after surgery (1 week and 1 month) for their dysphagia score with a standardized questionnaire. The surgical team preferences, experience and complexity with and without transillumination were evaluated. Ten OPMD patients (8 heterozygotes, 2 homozygotes for the commonmutation) underwent CPM for relieving dysphagia symptoms at medium size medical center in Israel between 2010 and 2019. Five patients had TA-CPM and the 5 patients had CPM without transillumination. All patients showed an improvement at follow-up examinations, 1 week and 1 month postoperative, including a decrease in dysphagia score and in choking and aspiration events, compared to their preoperative state. TA-CPM improved the surgical approach, reduced the difficulty of CPM and was preferred by the surgical team. From the patients' point of view, TA-CPM was as good as a non-transillumination approach in improving dysphagia. TA-CPM is a cheap, fast and simple technique to improve the surgical outcomes in CPM for patients with OPMD. TA-CPM navigates the surgeon, helps with anatomical orientation, improve the surgeon's comfortable, may shorten the duration of surgery and reduces potential errors. Improvement in dysphagia score was similar in both groups. This technique may improve myotomy procedures for dysphagia of other etiologies. Level of evidence: IV. Case series (with or without comparison). Endoscopic transillumination assisted myotomy.

Clinical Efficacy of Topical Nasal Pomegranate Fruit Extract for Chronic Rhinitis and Chronic Rhinosinusitis.

Objective: To evaluate the clinical efficacy of topical nasal Pomegranate Fruit Extract (PFE) for Chronic Rhinitis (CR), Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP), and Chronic Rhinosinusitis without Nasal Polyposis (CRSsNP). Methods: Prospective, double-blinded, randomized study including 111 consecutive patients, between April 2012 and January 2017, afflicted by CRSwNP, CRSsNP, and CR. Patients from each group were randomly assigned to either PFE treatment or placebo twice daily for 30 days. Therapeutic efficacy was assessed by Ear Nose and Throat, blood and tomographic examinations, and the SNOT-20 questionnaire. Results: CR patients treated with PFE suffered significantly less from thick nasal discharge, difficulty falling asleep, reduced productivity, reduced concentration, and sadness (P = .004, P = .02, P = .03, P = .007 and P = .02, respectively). Conclusions: Topical nasal PFE was found to have some benefits for CR patients, however, not for CRS with or without Nasal Polyposis.

Myiasis in Neglected Cutaneous Squamous Cell Carcinoma of the Head and Neck: Review of Management and Current Protocol Recommendations.

OBJECTIVE: To propose a first-aid management protocol for myiasis in neglected cutaneous squamous cell carcinoma (SCC) in the ED based on a recent literature review. DATA SOURCES: PubMed. STUDY SELECTION: Inclusion criteria were all series and case reports of primary/secondary cutaneous SCC with myiasis of the head and neck, including orbital SCC cases, published after 2005. DATA EXTRACTION: A total of 14 articles including 15 patients were included. DATA SYNTHESIS: Demographics, socioeconomic situation, site of the lesion, larvae species with bacterial suprainfection, and first-aid treatment options were discussed. Two representative cases are described. CONCLUSIONS: Large, ulcerated, necrotic, myiasis-burdened SCC lesions in the head and neck area present a challenge for treatment, and to date, no consensus regarding first-aid management exists. The authors' proposed four-pillar first-aid management scheme may be a valid option to rapidly improve wound condition through disinfection, pain relief, and malodor and discharge eradication as a bridge to surgery.

Does nasal surgery improve multilevel surgical outcome in obstructive sleep apnea: A multicenter study on 735 patients.

OBJECTIVE: Does nasal surgery affect multilevel surgical success outcome. METHODS: Prospective eight country nonrandomized trial of 735 obstructive sleep apnea (OSA) patients, who had multilevel palate and/or tongue surgery, divided into two groups, with or without nose surgery. RESULTS: There were 575 patients in nose group, 160 patients in no nose group. The mean age for nose group 44.6 ± 11.4, no nose group 44.2 ± 11.8. Mean preoperative BMI for nose group 27.5 ± 3.6, no nose group 27.5 ± 4.1, mean postoperative BMI nose group 26.3 ± 3.7, no nose group 27.1 ± 3.8 (P = .006). Mean preoperative AHI nose group 32.7 ± 19.4, no nose group 34.3 ± 25.0 (P = .377); and mean postoperative AHI nose group 13.5 ± 10.2, no nose group 17.1 ± 16.0 (P = .001). Mean preoperative ESS nose group was 11.3 ± 4.7, no nose group was 10.4 ± 5.4 (P = .051); and mean postoperative ESS nose group was 5.3 ± 3.2, no nose group was 6.7 ± 2.8 (P = .001). The nose group had higher percentage change (adjusted for age, gender, BMI) in AHI (33.7%, 95% CI 14% to 53.5%) compared to the no nose group (P = .001); the nose group also had more percentage change in ESS (37%, 95% CI 23.6% to 50.3%) compared to the no nose group (P < .001). Change in BMI did not affect AHI nor ESS change (Cohen effect 0.03 and 0.14, respectively). AHI change in both groups were also statistically significant in the mild OSA (P = .008) and the severe OSA (P = .01). Success rate of surgery for the nose group 68.2%, while the no nose group 55.0% (P = .002). CONCLUSION: Combining nose surgery in multilevel surgery improves surgical success. LEVEL OF EVIDENCE: IIC.

[BALLOON DILATION OF THE EUSTACHIAN TUBE - THE EXPERIENCE ESTABLISHED IN HILLEL YAFFE MEDICAL CENTER].

INTRODUCTION: The Eustachian tube ventilates the middle ear while keeping pathogens out. Obstructive dysfunction of the Eustachian tube is a common complaint, manifested by the inability to equilibrate middle ear pressure. Middle ear sequelae include inflammation, tympanic membrane retraction and rarely cholesteatoma. Balloon dilation is a new procedure for treating obstructive dysfunction of the Eustachian tube. OBJECTIVES: This research evaluates the outcome of balloon dilation of the Eustachian tube (BDET) performed at Hillel Yaffe Medical Center and compares results with those reported in global publications. METHODS: Patients indicating that ear pressure had significantly impacted their quality of life were recruited. Most received a conductive hearing loss audiogram and either a B or C tympanogram. BDET was performed. A 12-month follow-up survey was conducted, including an ETDQ7 questionnaire and repeat audiograms and tympanograms. RESULTS: A total of 16 patients were recruited and 24 BDETs were conducted. Aside from one patient, who received ambulatory treatment for subcutaneous emphysema, no patients had BDET complications; average ETDQ7 scores improved from 25.9 (n=20) to 15.3 (n=9) 12 months post-op. (P=0.001). CONCLUSIONS: BDET is a safe procedure and benefits those who suffer from an obstructed Eustachian tube. A comprehensive literature review also concludes that BDET is safe, that it relieves the obstructive Eustachian tube and is superior to conservative treatments. BDET is increasingly being used on a global scale and the Hillel Yaffe Medical Center is applying it in Israel.

Does drug-induced sleep endoscopy affect surgical outcome? A multicenter study of 326 obstructive sleep apnea patients.

OBJECTIVES/HYPOTHESIS: Our objective was to determine whether drug-induced sleep apnea (DISE) affects the successfulness of the surgical outcome. STUDY DESIGN: Prospective, seven-country, nonrandomized trial. METHODS: There were 326 consecutive obstructive sleep apnea (OSA) patients who had nose, palate, and/or tongue surgery included in the study. DISE was performed in only one group. RESULTS: There were 170 patients in the DISE group and 156 patients in no-DISE group. The mean preoperative body mass index (BMI) for the DISE group was 27.6 ± 4.6, whereas in the no-DISE group it was 28.1 ± 3.9 (P = .23). The mean preoperative systolic blood pressure (SBP) for the DISE group was 130.4 ± 16.7, whereas in the no-DISE group it was 142.9 ± 15.5 (P < .001). The mean preoperative diastolic blood pressure (DBP) for the DISE group was 81.4 ± 9.7, whereas in the no-DISE group it was 89.1 ± 9.7 (P < .001). The mean preoperative apnea-hypopnea index (AHI) for the DISE group was 32.6 ± 18.8, whereas in the no-DISE group it was 33.7 ± 19.6 (P = .61). The mean postoperative AHI for the DISE group was 15.9 ± 12.6, whereas in the no-DISE group it was 13.2 ± 8.8 (P = .023). The age-, gender-, BMI-adjusted percentage change in AHI for the DISE group was -48.4 ± 31.9, whereas in the no-DISE group it was -59.8 ± 18.6 (P < .001). The age-, gender-, and BMI-adjusted success rate for the DISE group was 66.5%, whereas in the no-DISE group it was 80.8% (P = .004). The age-, gender-, and BMI-adjusted change in SBP for the DISE group was -6.1 ± 8.6, whereas in the no-DISE group it was -13.3 ± 11.1 (P < .001). The age-, gender-, and BMI-adjusted change in DBP in the DISE group was -5.2 ± 12.1, whereas in the no-DISE group it was -12.4 ± 11.7 (P < .001). The mean age- and gender-adjusted change in BMI for the DISE group was -4.6 ± 12.9, whereas in the no-DISE group it was -6.3 ± 18.5 (P = .34). The Cohen effect of BMI on the overall AHI, lowest oxygen saturation, and blood pressure changes was 0.08. CONCLUSIONS: DISE may not significantly affect surgical success in OSA. LEVEL OF EVIDENCE: 2c Laryngoscope, 130:551-555, 2020.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

Breath volatolomics for diagnosing chronic rhinosinusitis.

PURPOSE: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases treated by primary care physicians. It is increasingly recognized that CRS and nasal polyposis (NP) comprise several disease processes with diverse causes. Hence, subgroups of sinusitis need to be differentiated so that patients can be screened appropriately and personalized medical treatment provided. PATIENTS AND METHODS: To address this need, we use a cross-reactive nanoarray based on either molecularly modified gold nanoparticles or molecularly modified single-walled carbon nanotubes, combined with pattern recognition for analyzing breath samples. Breath samples were collected from three groups of volunteers (total 71) at the Hillel Yaffe Medical Center: CRS, NP, and control. RESULTS: Nanoarray results discriminated between patients with sinusitis and the control group with 87% sensitivity, 83% specificity, and 85% accuracy. The system also discriminated well between the subpopulations: 1) CRS vs control (76% sensitivity, 90% specificity); 2) CRS vs NP (82% sensitivity, 71% specificity); and 3) NP vs control (71% sensitivity, 90% specificity). CONCLUSION: This preliminary study shows that a nanoarray-based breath test for screening population for sinusitis-related conditions is feasible.

Traumatic Optic Neuropathy and Monocular Blindness following Transnasal Penetrating Optic Canal Injury by a Wooden Foreign Body.

PURPOSE: To report a case of right eye blindness due to a penetrating injury in the contralateral nostril. METHODS: This is a case report of a 67-year-old patient who presented to the emergency room complaining of transient blurred vision in his right eye after falling on a small branch with no apparent injury besides minor lacerations. The following day, the patient experienced blindness in the right eye. Physical examination revealed small lacerations on his left forehead and optic neuropathy on the right side with no other obvious discerning physical or imaging abnormalities. RESULTS: After elevated suspicion and reassessment of the neuroimaging findings, a radiolucent track was observed in the nasal cavity, continuing up from the left nostril to the right optic nerve. Transnasal endoscopic surgery was performed and a long wooden branch was removed from the nasal cavity. CONCLUSION: A nasally penetrating wooden foreign body can cause traumatic optic neuropathy and vision loss on the unaffected side and can be very difficult to locate and image without any clear external evidence as to its presence. This case highlights the importance of maintaining a high level of suspicion in these types of cases.

Oculopharyngeal Muscular Dystrophy and Inherited Retinal Dystrophy in Bukhara Jews Due to Linked Mutations in the PABPN1 and NRL Genes.

AIM: We have previously described two unrelated Bukhara Jews (BJs) with a combination of oculopharyngeal muscular dystrophy (OPMD) and inherited retinal dystrophy (IRD), because of mutations in two linked genes: PABPN1 and NRL. Here we investigated the prevalence of the NRL mutation among BJs with OPMD. MATERIALS AND METHODS: PABPN1 and NRL mutation testing were performed by polymerase chain reaction amplification and direct sequencing on two cohorts of Bukhara Jewish patients: OPMD patients (with or without IRD) and IRD patients (without OPMD). RESULTS: Of 24 unrelated chromosomes from Bukhara Jewish OPMD patients, 19 (79%) harbored the NRL mutation. In contrast, the NRL mutation was not detected in Bukhara Jewish patients diagnosed with IRD but without OPMD. CONCLUSIONS: Our findings provide an explanation for the reoccurrence of IRD in Bukhara Jewish OPMD homozygotes. Moreover, they indicate that Bukhara Jewish OPMD patients are at high risk for carrying the NRL mutation, and should be offered appropriate genetic counseling and testing.

Primary solitary intralabyrinthine schwannoma: A report of 7 cases and a review of the literature.

Intralabyrinthine schwannomas (ILSs) are uncommon benign tumors that originate in the Schwann cell sheath of the intralabyrinthine distal branches of the vestibulocochlear nerve. They have no initial involvement in the internal auditory canal, although that might develop later. These lesions can arise inside the cochlea, originate in the vestibule or, in rare cases, develop in the semicircular canals. From these sites, spread might take place via the anatomic connections between the perilymphatic spaces in the scala vestibuli and the anterior vestibule. Thus, ILSs centered in the cochlea might involve the vestibule, and those originating in the vestibular end organs would reach the cochlea. Presenting signs and symptoms include a progressive or sudden sensorineural hearing loss (which occurs in more than 95% of patients), as well as tinnitus and vertigo. Magnetic resonance imaging characteristics include sharp circumscription and hypointensity on thin, heavily T2-weighted 3D images and strong enhancement after gadolinium administration on T1-weighted images. We describe a series of 7 cases of primary ILS that were managed at two of our institutions. We also discuss the need for a comprehensive otoneurologic evaluation that encompasses the functional derangement and the tumor location as delineated by MRI, and we describe the treatment options.

Homozygosity for a Recessive Loss-of-Function Mutation of the NRL Gene Is Associated With a Variant of Enhanced S-Cone Syndrome.

PURPOSE: To investigate the genetic basis for severe visual complaints by Bukharan Jewish patients with oculopharyngeal muscular dystrophy (OPMD). METHODS: Polymerase chain reaction amplification and direct sequencing were used to test for NRL, PABPN1, and NR2E3 mutations. Complete ophthalmic examination included best-corrected visual acuity, biomicroscopic examination, optical coherence tomography, and fundus autofluorescence. Detailed electroretinography (ERG) testing was conducted including expanded International Society for Clinical Electrophysiology of Vision protocol for light-adapted and dark-adapted conditions, measurements of S-cone function, and ON-OFF light-adapted ERG. RESULTS: The index patients were homozygotes for both a dominant mutation of the PABPN1 gene, (GCN)13, and a recessive mutation of the NRL gene, p.R31X, on chromosome 14q11.1, leading to early-onset OPMD accompanied by night blindness and reduced visual acuity. No mutations were found in the NR2E3 gene. Both patients were of Bukharan Jewish origin, but from unrelated families. Electroretinography responses of both patients were dominated by short-wavelength-sensitive mechanisms, with no detectable rod function, similar to the ERG responses of individuals with enhanced S-cone syndrome (ESCS) due to NR2E3 mutations. Heterozygotes for the PABPN1 and NRL mutations demonstrated normal fundi and ERG responses. CONCLUSIONS: Homozygosity for the recessive NRL mutation described here appears to be associated with a distinct retinal phenotype, demonstrating ERG characteristics similar to those of ESCS patients. This report expands the spectrum of NRL recessive mutations, as well as the genetic spectrum of ESCS, and indicates a new syndrome of OPMD with an ESCS-like phenotype.

Susac's Syndrome: A Case with Unusual Cardiac Vestibular and Imaging Manifestations.

Susac's syndrome (SS) is a disease of the microvasculature of the retina, brain, and inner ear. We describe a patient with unusual manifestations of SS with possible involvement of the brainstem, cardiac arrhythmia, and MRI findings lacking the characteristic lesions found in Susac's syndrome.