Criminal Law: Demise of “Status”—“Act” Distinction in Symptomatic Crimes of Narcotic Addiction

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X-linked cataract and Nance-Horan syndrome are allelic disorders

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication–triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Laurence-Moon-Bardet-Biedl syndrome. Clinical,electrophysiological and genetic aspects.

The study included 44 Scandinavian individuals with the autosomal recessive inherited Laurence-Moon-Bardet-Biedl syndrome. Inclusion criteria were retinal dystrophy plus at least 2 more of the remaining traditional cardinal signs of the syndrome: obesity, polydactyly, hypogenitalism and mental retardation. The study showed that the patients had an early onset of night blindness and a poor visual prognosis. No rod ERG-responses to dim blue light were found, even in the youngest-3 years old. No one exceeding the age of 16 had a best corrected visual acuity of more than 0.1. The fundus picture was an atypical retinitis pigmentosa with macular pigments previous to any bone spicules. Birth weight and -length were within normal limits, but obesity appeared in early childhood and proceeded to profuse overweight during adolecence. Final height was slightly reduced. Typical skeletal anomalies were polydactyly, short and broad metacarpal bones and flat joint surfaces of the metacarpo- or metatarso-phalangeal joints. Hypogenitalism was noted in nearly all the men but only as an exception in the women. Most patients seemed to have good mental resources. Renal disease was a common cause of death. We found significantly higher frequencies of small or missing teeth and short roots compared to a control group. Substantial variation of the clinical signs was demonstrated both between families and between affected siblings in 11 families with 2-3 syndrome members. These families were included in a genetic study of 29 similar families where linkage was confirmed to the BBS1, BBS4 and BBS2 loci on chromosomes 11, 15 and 16. No clear clinical distinctions were apparent between the families linked to the different loci. Overlapping of clinical signs from the subgroups Laurence-Moon, Bardet-Biedl and Alström syndromes were observed within the same patient or family. The typical features in our Laurence-Moon-Bardet-Biedl syndrome patients were: retinal dystrophy, obesity, dental anomalies, skeletal anomalies of hands and feet, hypogenitalism in men and renal disease

Corneal Involvement in Congenital Aniridia.

PURPOSE:: The purpose of this research is 2-fold. First of all, the level of keratopathy development in patients with congenital aniridia is studied. In addition, a correlation between the effects of ocular surgery on the severity of keratopathy is made. METHODS:: A thorough search for the total number of patients with aniridia in Sweden and Norway was performed. One hundred eighty-one patients were identified and 124 (69%) of these were examined. Three artificial eyes, 16 eyes with corneal transplants, and 1 eye with a corneal limbal allograft were excluded from the study. All participating patients underwent clinical ophthalmologic examinations, including photographs, and their medical history was recorded. A slit lamp was used to examine the presence of keratopathy. RESULTS:: Visible keratopathy was found in 80% of the eyes. Keratopathy that caused impaired visual acuity was found in 26% of the eyes. The study displayed a significant correlation between the level of keratopathy and the patient's age. A significant correlation between the level of keratopathy and intraocular surgery exists. This is irrespective of the patient's age. The study also found that irrespective of the patient's age, a significant correlation between the level of keratopathy and impaired corneal sensitivity exists. CONCLUSIONS:: This research identified the presence of visible keratopathy in 80% of eyes. In addition, 26% of eyes had a keratopathy level that caused visual disturbances. The study showed that the prevalence and severity of keratopathy increased with the patient's age. Further conclusions are that intraocular surgery increases the severity of keratopathy and that the severity of keratopathy is correlated to reduced corneal sensitivity. Finally, extreme care should be taken when selecting patients for intraocular surgery because this procedure can trigger the development of keratopathy

Epidemiology of aniridia in Sweden and Norway.

Purpose: To investigate the epidemiology of aniridia in the populations of Sweden and Norway. Methods: A thorough search for aniridia patients has been performed in Sweden and Norway. All participants had a clinical ophthalmological examination documented through photography. Blood samples were taken for mutation analysis and pedigrees were established. Results: A total of 181 patients with aniridia were identified in the two countries. This gives an age-specific prevalence of 1:72 000 in the entire region, 1:70 000 in Sweden and 1:76 000 in Norway. A total of 124 individuals (69%) were examined. Male/female ratio was 0.94 (Sweden 0.85 and Norway 1.2). Mean age of the examined patients was 29 years and median age 25 years. We did not find any significant age difference between the two countries. The mean visual acuity (VA) was 0.19 (Sweden 0.19 and Norway 0.18).The number of families with more than one affected member was 31 and the number of sporadic cases was 40. Conclusion: We have done a thorough search of the literature, but we have found no earlier studies describing aniridia in an entire country and only a few reports from larger areas. We assume that most aniridia patients have been found and the aniridia prevalence of 1:72 000 can be regarded as well supported. Further studies on other aspects of aniridia are in progress, and information from these can contribute to guidelines for the care of patients with this rare but serious disease

Aniridia among children and teenagers in Sweden and Norway.

Purpose: To investigate patients under the age of 20 with aniridia in Sweden and Norway in order to estimate the prevalence of aniridia, to describe clinical signs and identify complications in the young, which will help improve diagnostic tools and treatment. Methods: A thorough search for patients with aniridia (of all ages) was performed. Sixty-two of the 181 patients were under the age of 20. Fifty-two of them were examined and they constituted the study population. Patient history was obtained and all participants underwent clinical ophthalmologic examination, including photography. Blood samples were taken for mutation analysis. Results: Epidemiological data are only based on the results in Sweden. The age-specific prevalence in Sweden was 1:47 000, male/female ratio was 0.57, mean age 12 years and median age 14 years. The proportion of sporadic cases including WAGR (Wilms tumour, Aniridia, Genitourinary abnormalities, Mental Retardation) and Gillespie syndrome (aniridia, cerebellar ataxia and mental retardation) was 48%. In the entire study population (Sweden and Norway), the mean visual acuity (VA) was 0.2 (range 0.04-0.9). We found VA < 0.3 in 80% and <0.1 in 18% of the patients. Twenty-two patients (42%) had one or more of the sight threatening complications such as cataract/lens luxation, corneal clouding or glaucoma. Conclusion: Descriptions of aniridia in the younger are rare. This study shows that aniridia seems to be more common than previously estimated and that some complications appear early in life. Watchfulness as regards these complications and regular examinations are essential even in the youngest

In Vivo Morphology of the Limbal Palisades of Vogt Correlates With Progressive Stem Cell Deficiency in Aniridia-Related Keratopathy

Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients.Funding Agencies|Crown Princess Margaretas Foundation for the Visually Impaired||Carmen and Bertil Regners Foundation for Research in Eye Disease||County Council of Ostergotland||Konung Gustav V and Drottning Viktorias Frimurarestiftelse||The Swedish Research Council||Aniridia Norway||</p