A Next Generation Sequencing custom gene panel as first line diagnostic tool for atypical cases of syndromic obesity: Application in a case of Alström syndrome

Obesity phenotype can be manifested as an isolated trait or accompanied by multisystem disorders as part of a syndromic picture. In both situations, same molecular pathways may be involved to different degrees. This evidence is stronger in syndromic obesity, in which phenotypes of different syndromes may overlap. In these cases, genetic testing can unequivocally provide a final diagnosis. Here we describe a patient who met the diagnostic criteria for Alström syndrome only during adolescence. Genetic testing was requested at 25 years of age for a final confirmation of the diagnosis. The genetic diagnosis of Alström syndrome was obtained through a Next Generation Sequencing genetic test approach using a custom-designed gene panel of 47 genes associated with syndromic and non-syndromic obesity. Genetic analysis revealed a novel homozygous frameshift variant p.(Arg1550Lysfs*10) on exon 8 of the ALMS1 gene.This case shows the need for a revision of the diagnostic criteria guidelines, as a consequence of the recent advent of massive parallel sequencing technology. Indications for genetic testing reported in these currently accepted diagnostic criteria for Alström syndrome, were drafted when sequencing was expensive and time consuming. Nowadays, Next Generation Sequencing testing could be considered as first line diagnostic tool not only for Alström syndrome but, more generally, for all those atypical or not clearly distinguishable cases of syndromic obesity, thus avoiding delayed diagnosis and treatments. Early diagnosis permits a better follow-up and pre-symptomatic interventions.     

Performance of manual ventilation: how to define its efficiency in bench studies? A review of the literature

Bench studies have become the preferred way to evaluate the performance of airway equipment, since clinical trials are not specifically required before marketing these devices. However, it is difficult to assess the efficiency of ventilation without recording physiological data. This review analyses how efficiency of manual ventilation has been defined in recent studies, and how their results may be affected. We searched electronic databases from 2000 to April 2014. The main inclusion criterion was the analysis of performance of ventilation. Nine relevant articles were selected from 53 eligible publications. Most studies used the same parameters; tidal volume and ventilation rate. However, there were significant differences between the definitions of performance of ventilation, both in terms of criteria of judgement and methods of analysis. None of these approaches is able to provide a clear understanding of variability of ventilation during a given period. A new definition may increase the relevance of bench studies to clinical medicine, by more appropriately assessing the performance of ventilation.     

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients

Neurological Sciences - Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for...