C19orf12 mutation leads to a pallido-pyramidal syndrome.

Pallido-pyramidal syndromes combine dystonia with or without parkinsonism and spasticity as part of a mixed neurodegenerative disorder. Several causative genes have been shown to lead to pallido-pyramidal syndromes, including FBXO7, ATP13A2, PLA2G6, PRKN and SPG11. Among these, ATP13A2 and PLA2G6 are inconsistently associated with brain iron deposition. Using homozygosity mapping and direct sequencing in a multiplex consanguineous Saudi Arabian family with a pallido-pyramidal syndrome, iron deposition and cerebellar atrophy, we identified a homozygous p.G53R mutation in C19orf12. Our findings add to the phenotypic spectrum associated with C19orf12 mutations.

Unusual association of diseases/symptoms: Encephalitis with herpes simplex-2 in the cerebrospinal fluid and anti-RI (ANNA-2) antibodies: an infectious or a paraneoplastic syndrome?

We report on a 70-year-old woman with partial complex status epilepticus who was initially diagnosed with herpes simplex-2 (HSV-2) encephalitis, based on brain magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) lymphocytic pleocytosis and HSV-2 DNA detection by polymerase chain reaction (PCR) in the CSF, but without improvement on intravenous acyclovir. Anti-Ri antibodies were positive and computed tomography (CT) investigations revealed a small cell carcinoma at biopsy suggesting paraneoplastic encephalitis. The outcome was unfavourable and the autopsy showed typical features of paraneoplastic encephalitis but no evidence of viral inclusions. This case report is interesting because: (1) it is the first report of an autopsy proven paraneoplastic widespread encephalitis with anti-Ri antibodies; (2) despite a positive HSV-2 PCR in the CSF, there was no sign of herpetic infections of the nervous system; and (3) it illustrates the fact that if paraneoplastic antibodies are usually good markers of the underlying tumour, they are not always predictive of neurological deficits.

Brugada syndrome unmasked by accidental inhalation of gasoline vapors.

Loss-of-function mutations in the gene SCN5A can cause Brugada syndrome (BrS), which is an inherited form of idiopathic ventricular fibrillation. We report the case of a 46-year-old patient, with no previous medical history, who had ventricular fibrillation after accidental inhalation of gasoline vapors. His electrocardiogram (ECG) showed a typical type-1 BrS pattern that persisted after the acute event. Genetic investigations allowed the identification of a novel SCN5A mutation leading to a frame-shift and early termination of the channel protein. Biochemical and cellular electrophysiology experiments confirmed the loss-of-function of the mutant allele. The patient was implanted with a cardioverter/defibrillator.

Lymphomes des annexes de l'oeil au cours du syndrome de Gougerot-Sjögren [Lymphomas of the ocular adnexa in Gougerot-Sjögren syndrome. Apropos of 4 cases].

The risk of malignant B cell lymphoma is increased in Sjögren's syndrome (SS). Orbital localization seems infrequent. We report 4 cases of malignant lymphoma (ML) occurring in 4 women aged 47 to 77 years, with primary SS in 3 cases, located to the conjunctiva in 2 cases, the lacrymal gland in 1 case and the eyelid in 1 case. The interval between the diagnosis of SS and orbital ML varied from 6 months to 15 years. All 4 lymphomas were of the B cell type, low histopathologic grade, with monoclonal gammopathy in 1 case. Extraocular lymphoma was initially present in 1 case. ML remained localized in 2 cases with a follow-up of 4 and 6 years. Two patients treated by excisional biopsy alone are in complete remission 3 and 6 years later. The 2 other patients treated with orbital radiotherapy and chemotherapy died rapidly (transformation into a high grade malignancy in 1 case). We conclude that clinical, immunopathologic features, as well as prognosis and treatment of ocular adnexa ML in SS are similar to those of primary ML without SS.

Williams-Beuren syndrome TRIM50 encodes an E3 ubiquitin ligase.

Williams-Beuren syndrome (WBS) is a neurodevelopmental and multisystemic disease that results from hemizygosity of approximately 25 genes mapping to chromosomal region 7q11.23. We report here the preliminary description of eight novel genes mapping within the WBS critical region and/or its syntenic mouse region. Three of these genes, TRIM50, TRIM73 and TRIM74, belong to the TRIpartite motif gene family, members of which were shown to be associated to several human genetic diseases. We describe the preliminary functional characterization of these genes and show that Trim50 encodes an E3 ubiquitin ligase, opening the interesting hypothesis that the ubiquitin-mediated proteasome pathway might be involved in the WBS phenotype.

Syndrome d'hyperstimulation ovarienne [The syndrome of ovarian hyperstimulation].

The ovarian hyperstimulation syndrome (SHO) can be defined as an iatrogenic pathology induced by active substances administered for controlling follicular maturation and ovulation. The etiology, the physiopathology, the diagnostic and therapeutic methods available are discussed. A theoretical model, based on clinical data, allows identification of a set of criteria which should help determining prospectively the chances of development of such a pathology.

Outcome of patients with acute coronary syndrome in hospitals of different sizes in Switzerland

Objective: To assess the impact of patient admission in different hospital types in Switzerland on early in-hospital and 1-year outcomes in patients with acute coronary syndrome (ACS).Methods: From 1997 to 2009, 31,010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary teaching institutions with 24 hour/7 day cardiac catheterization facilities were classified as type A hospitals, all others as type B. One-year outcome was studied in a subgroup of patients admitted after 2005. Multivariate logistic regression models were used to calculate the odds ratios (OR with 95%CI) for independent predictors of mortality and major adverse cardiac events (MACE).Results: There were 11 type A hospitals with admissions of 15,987 (52%) patients and 65 type B hospitals with 15,023 (48%) patients. Patients initially admitted into B hospitals were older, more frequently female, hypertensive and diabetic, had more severe comorbidities and more frequently NSTE-ACS/UA. They were less likely to receive aspirin, clopidogrel and GPIIb/IIIa antagonists. STE-ACS patients initially admitted into B hospitals received more thrombolysis than those admitted into A hospitals, but less percutaneous coronary intervention (PCI). From the patients admitted to B hospitals, 5271 (35%) were transferred for intervention. Crude in-hospital mortality and MACE were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients initially admitted into B hospitals, but no differences were found for MACE. Hospital type, after adjustment for age, risk factors, type of ACS and co-morbidities, was not an independent predictor of in-hospital mortality (OR 0.94; 0.76-1.16), in-hospital MACE (0.98; 0.82-1.17), 1-year mortality or 1-year MACE (1.06; 0.85-1.33). Analysis of the time of admission indicated a crude outcome in favor of hospitalization during duty-hours but no significant effect could be documented for 1-year outcome.Conclusion: ACS patients admitted to type B hospitals were older, had more severe co-morbidities, more NSTEACS and received less intensive treatment. However, after correcting for baseline inequalities, early and mid-term outcomes were similar regardless of hospital type. Ultimate patient outcome thus does not appear to be influenced by the type of hospital where the initial admission takes place. Appropriate early referral of selected patients probably partly explains this finding.

Le syndrome douloureux abdominal (SDA) aux urgences: quelle analgésie [Acute abdominal pain: what about analgesia]

Acute abdominal pain tends not to be treated by surgeons and emergency physicians. However, literature has become clear that analgesics are effective and do not disturb clinical examination, diagnostic process and do not delay surgery. Thus, early treatment of acute abdominal pain is recommended. In the absence of scientific evidence, protocols must be established by each institution and validated by quality process.

Acute reversible Charles Bonnet syndrome precipitated by sudden severe anemia.

PURPOSE: To report the sudden onset of reversible Charles Bonnet syndrome precipitated byacute severe anemia. METHODS: The charts of three patients (Usher syndrome, bilateral macular degeneration, and bilateral retinal vein occlusion) with acute Charles Bonnet syndrome in the setting of severe anemia were reviewed. RESULTS: Anemia resulted from bladder surgery, recto-colitis, and severe urinary tract infection. Hemoglobin ranged from 78 to 86 g/L. Decreased visual acuity and formed visual hallucinations (giants, flowers, animals) were present in all three patients. Rapid reversal of Charles Bonnet syndrome and visual acuity improvement followed blood transfusion. CONCLUSIONS: Acute severe anemia can precipitate Charles Bonnet syndrome, which may be reversible by blood transfusion.

Congenital high airway obstruction syndrome and airway reconstruction: an evolving paradigm.

OBJECTIVES: To refine the classic definition of, and provide a working definition for, congenital high airway obstruction syndrome (CHAOS) and to discuss the various aspects of long-term airway reconstruction, including the range of laryngeal anomalies and the various techniques for reconstruction. DESIGN: Retrospective chart review. PATIENTS: Four children (age range, 2-8 years) with CHAOS who presented to a single tertiary care children's hospital for pediatric airway reconstruction between 1995 and 2000. CONCLUSIONS: To date, CHAOS remains poorly described in the otolaryngologic literature. We propose the following working definition for pediatric cases of CHAOS: any neonate who needs a surgical airway within 1 hour of birth owing to high upper airway (ie, glottic, subglottic, or upper tracheal) obstruction and who cannot be tracheally intubated other than through a persistent tracheoesophageal fistula. Therefore, CHAOS has 3 possible presentations: (1) complete laryngeal atresia without an esophageal fistula, (2) complete laryngeal atresia with a tracheoesophageal fistula, and (3) near-complete high upper airway obstruction. Management of the airway, particularly in regard to long-term reconstruction, in children with CHAOS is complex and challenging.

Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia.

We sought to explore the genotype-phenotype of Jervell and Lange-Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Six families with at least one JLNS-affected member attended our clinic between 2011 and 2013. Retrospective and prospective clinical data were collected and genetic investigation was performed. Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients. The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T. All living JLNS patients except one had a QTc of >500 ms and a history of recurrent syncope. β-Blockers abolished the cardiac-related events in all patients except two siblings with homozygous Ile567Thr mutation. Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients. Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias. Mutations detected in this study will be advantageous in tribe and region-specific cascade screening of LQTS in Saudi Arabia.