Angelman syndrome: A review highlighting musculoskeletal and anatomical aberrations

Angelman's syndrome (AS) is a genetic neurodevelopment disorder. The cause is a known abnormality involving the maternal inherited ubiquitin‐protein ligase (UBE3A) gene. Clinical characteristics universal to the disorder are well documented in the literature and include developmental delay, seizures, ataxia, altered tone, severely impaired speech and intellect, as well as an overall happy demeanor, frequent bouts of laughter, and hypermotoric behavior. Associated with this disorder are several musculoskeletal aberrations. To date, a review of case studies reporting on these musculoskeletal changes has not been carried out. Thus, the purpose of this paper was to provide an overview of the musculoskeletal changes present in individuals with AS. In our review of 21 case reports from 1965–2013, the most consistently reported anatomical changes were of the craniofacial region. These include microcephaly, brachycephaly, a palpable occipital groove, prognathism, and wide spaced teeth. Other musculoskeletal abnormalities less frequently reported in the literature include scoliosis, excessive lumbar lordosis, and pes planus. Given that the majority of the case reports reviewed was of young children, the possibility of underreporting musculoskeletal changes which may manifest in the later years of life may be present. Early diagnosis and interventions to minimize secondary complications are crucial to maintain quality of life. An overall multidisciplinary approach is emphasized to maximize developmental potential for these individuals. Future prospective studies that follow patients into adulthood are needed to better understand the prevalence and development of secondary musculoskeletal changes, which in turn can inform intervention techniques and preventative measures. Clin. Anat. 29:561–567, 2016. © 2015 Wiley Periodicals, Inc.     

CHRNB3 is more strongly associated with Fagerström Test for Cigarette Dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results

AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.     

Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

Controversies in neuro-ophthalmology: Steroid therapy for traumatic optic neuropathy

Background:There is an increase in the incidence of traumatic optic neuropathy (TON) due to increasing urbanization and rapid spurt in the number of motor vehicles on the road. Despite early presentation and ease of diagnosis the visual outcomes in TON are still limited. There is also significant confusion about the timing, dose and efficacy of steroid treatment in its management.Purpose:To provide a clinical update of the pros and cons of steroid therapy for TON.Design:The paper is a retrospective review of the currently available literature in the English language indexed in PubMed.Methods:A PubMed search was conducted by the authors using the following terms: Traumatic optic neuropathy, megadose, steroids, methylprednisolone. Relevant original articles, review articles, and case reports related to the topic of discussion were evaluated and discussed in the paper.Results:There is no prospective randomized control trial evaluating the effect of steroids in TON. There are varying reports on the effect of steroid therapy from significant improvement to no difference compared to observation.Conclusion:The decision to give steroids to patients with TON has to be on an individual case to case basis and must involve informed consent from the patient. There are documented advantages and disadvantages of steroid therapy and a prospective, randomized, controlled trial is necessary comparing steroids, surgery and observation before definitive management can be evolved.     

Zika Virus and the Eye

Zika virus (ZIKV), a mosquito-borne flavivirus, is the latest global health concern. Transmission is mainly via Aedes mosquitoes and the infection can be diagnosed on molecular or serologic testings. It typically causes a mild self-remitting illness of low-grade fever, maculopapular rash, and myalgia, but when severe, it is associated with neurological deficits and congenital structural defects. Ocular manifestations are usually mild like nonpurulent conjunctivitis in adults, though it may be linked to uveitis, maculopathy, and hypertensive iridocyclitis. Ocular signs seem to be more significant in congenital ZIKV—macular pigment mottling, neuroretinal atrophy with macular involvement, iris coloboma, and changes in retinal vasculature are noted in infants with infected mothers. Risk factors include ZIKV infection in first trimester and smaller cephalic diameter at birth. Hence, ophthalmic examination in newborns is now recommended. Currently, prevention and active surveillance are integral as there is no known vaccine, and treatment is only symptomatic.     

Rare occurrence of fatal Candida haemulonii peritonitis in a diabetic CAPD patient

A 68-year-old diabetic chronic kidney disease patient on continuous ambulatory peritoneal dialysis for two years developed Candida haemulonii peritonitis without any predisposing factors. There is no effective treatment for this fungus. A peritoneal biopsy showed morphological changes of acute inflammation and chronicity.