Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature

Mutations in the FKRP gene result in phenotypes with severe forms of congenital muscular dystrophies (CMD) and limb-girdle muscular dystrophies. We present a Mexican patient with a pathogenic homozygous mutation in the FKRP gene (c.1387A > G, p.Asn463Asp) and CMD with radiological brain anomalies as disseminated hyperintensity lesions and discrete generalized cortical atrophy. These findings have not been reported to the best of our knowledge in other patients with the same mutation. The mutation c.1387A > G, p.Asn463Asp in the FKRP gene has been described to have a founder effect in central Mexico, since all the patients described to date are of Hispanic origin. Therefore, we emphasize studying mutations in the FKRP gene in Hispanic pediatric patients with clinical suspicion of CMD. Clinical and molecular diagnosis of specific CMD subtypes is needed to help clarify the prognosis, management, and genetic counseling to the patient and families.

Screening diabetic retinopathy using an automated retinal image analysis (ARIA) system in Mexico: independent and assistive use cases

Background: The automated screening of patients at risk of developing diabetic retinopathy (DR), represents an opportunity to improve their mid-term outcome and lower the public expenditure associated with direct and indirect costs of a common sight-threatening complication of diabetes. Objective: In the present study, we aim at developing and evaluating the performance of an automated deep learning-based system to classify retinal fundus images from international and Mexican patients, as referable and non-referable DR cases. In particular, we study the performance of the automated retina image analysis (ARIA) system under an independent scheme (i.e. only ARIA screening) and two assistive schemes (i.e., hybrid ARIA + ophthalmologist screening), using a web-based platform for remote image analysis. Methods: We ran a randomized controlled experiment where 17 ophthalmologists were asked to classify a series of retinal fundus images under three different conditions: 1) screening the fundus image by themselves (solo), 2) screening the fundus image after being exposed to the opinion of the ARIA system (ARIA answer), and 3) screening the fundus image after being exposed to the opinion of the ARIA system, as well as its level of confidence and an attention map highlighting the most important areas of interest in the image according to the ARIA system (ARIA explanation). The ophthalmologists' opinion in each condition and the opinion of the ARIA system were compared against a gold standard generated by consulting and aggregating the opinion of three retina specialists for each fundus image. Results: The ARIA system was able to classify referable vs. non-referable cases with an area under the Receiver Operating Characteristic curve (AUROC), sensitivity, and specificity of 98%, 95.1% and 91.5% respectively, for international patient-cases; and an AUROC, sensitivity, and specificity of 98.3%, 95.2%, 90% respectively for Mexican patient-cases. The results achieved on Mexican patient-cases outperformed the average performance of the 17 ophthalmologist participants of the study. We also find that the ARIA system can be useful as an assistive tool, as significant specificity improvements were observed in the experimental condition where participants were exposed to the answer of the ARIA system as a second opinion (93.3%), compared to the specificity of the condition where participants assessed the images independently (87.3%). Conclusions: These results demonstrate that both use cases of ARIA systems, independent and assistive, present a substantial opportunity for Latin American countries like Mexico towards an efficient expansion of monitoring capacity for the early detection of diabetes-related blindness.

Comparison of Genetic Variants and Manifestations of OTUD6B-Related Disorder: The First Mexican Case

The intellectual disability syndrome characterized by seizures and dysmorphic features was initially described in 2017 and was associated with genetic variants in the OTUD6B gene, identified by exome sequencing (ES) in a large cohort. This multisystem disorder primarily affects the central nervous system, the gastrointestinal, and the skeletal systems. In this article, we describe the first Mexican patient diagnosed by ES. The homozygous c.433C>T (p.Arg145*) variant of the OTUD6B gene confirmed this intellectual disability syndrome. In addition to seizures and other more frequently reported manifestations of this condition, this is the third patient with associated hypothyroidism and hypogammaglobulinemia, underscoring the value of screening for these conditions in other patients. The current challenge with this patient is to ensure medical management of his seizures and provide him with a better quality of life. The possibilities of additional therapeutic approaches may increase by understanding the physiopathology of the involved pathways.