Visual Function in Children with GNAO1-Related Encephalopathy.

BACKGROUND: GNAO1-related encephalopathies include a broad spectrum of developmental disorders caused by de novo heterozygous mutations in the GNAO1 gene, encoding the G (o) subunit α of G-proteins. These conditions are characterized by epilepsy, movement disorders and developmental impairment, in combination or as isolated features. OBJECTIVE: This study aimed at describing the profile of neurovisual competences in children with GNAO1 deficiency to better characterize the phenotype of the disease spectrum. METHODS: Four male and three female patients with confirmed genetic diagnosis underwent neurological examination, visual function assessment, and neurovisual and ophthalmological evaluation. Present clinical history of epilepsy and movement disorders, and neuroimaging findings were also evaluated. RESULTS: The assessment revealed two trends in visual development. Some aspects of visual function, such as discrimination and perception of distance, depth and volume, appeared to be impaired at all ages, with no sign of improvement. Other aspects, reliant on temporal lobe competences (ventral stream) and more related to object-face exploration, recognition and environmental control, appeared to be preserved and improved with age. SIGNIFICANCE: Visual function is often impaired, with patterns of visual impairment affecting the ventral stream less.

Sexual Satisfaction and Quality of Life in Cardiovascular Patients: The Mediating Role of Anxiety.

BACKGROUND: Cardiovascular diseases represent one of the most important problems for public health. Research indicates that elderly patients consider sexual satisfaction as a fundamental aspect of their quality of life and a better sexual function is related to higher general wellbeing. OBJECTIVE: The main objective of this study was to investigate the mediating role of anxiety and depression in the relationship between quality of life and sexual satisfaction in cardiovascular (CVD) patients. METHODS: The sample comprised 128 adult patients, males and females, hospitalized in a Cardiology Rehabilitation clinical center. To collect data, the following were used: a demographic information sheet, the left ventricular ejection fraction (EF) to evaluate cardiac function, cardiovascular diagnosis type, the HADS scale to evaluate anxiety and depression states, a test for sexual satisfaction evaluation (SAS) and the SF-36 survey to measure quality of life. RESULTS: The results indicated that only SF-36 physical health is indirectly related to SAS through its relationship with anxiety. CONCLUSION: A mediating model was proposed to explore the underlying association between sexual satisfaction and quality of life. We recommend investigating perceived general health and sexuality as clinical indicators for therapeutic decisions and risk evaluation for the management of cardiovascular diseases.

[ANMCO Position paper: Amyloidosis for the clinical cardiologist. A "clinical primer" from the ANMCO Rare Disease Working Group]. / Position paper ANMCO: L'amiloidosi per il cardiologo clinico. Un "clinical primer" dell'Area Malattie Rare ANMCO.

Cardiac amyloidosis, in the three forms of immunoglobulin light chain (AL), transthyretin (ATTR) wild type (ATTRwt) and mutated (ATTRv) amyloidosis, is an increasingly known and recognized disease in the cardiovascular setting. The first stage of the patient's journey is the clinical suspicion of the disease, which is placed, in presence of a hypertrophic phenotype, by the identification of red flags, both extracardiac and cardiac clues whose presence increase the probability of being faced with a patient with this disease. The second stage is represented by diagnosis, which occurs with certainty through the identification of amyloid substance in cardiac tissue. This stage is spotted in wo parts, i.e. disease confirmation and disease etiology definition (AL vs ATTRwt vs ATTRv). However, it is possible in some selected cases to make a diagnosis of ATTR without the need for tissue assessment, in presence of a positive grade 2-3 bisphosphonate scintigraphy and absence of monoclonal component. Once the diagnosis has been made, the third stage is the assessment of prognosis, the fourth is the patient therapy pathway and fifth is the follow-up plan. Prognosis evaluation is based on different staging systems at the onset of the disease, whose applicability in the era of new effective therapies is still to be defined. To date, the transthyretin tetramer stabilizer tafamidis is the only approved treatment for both wild-type and mutant ATTR cardiomyopathy without polyneuropathy, while ATTRv with associated neuropathy can benefit from treatment with patisiran, an inhibitor of hepatic protein synthesis. Therapies for complications and comorbidities, must be addressed individually, due to the lack of specific clinical trials on this category of patients. In fact, it is important to take into consideration the risks linked to the use of some drugs due to the infiltration of the conduction tissue by the amyloid substance, which increases the risk of bradycardia and heart blocks, the tendency towards hypotension and the increased thromboembolic risk. It is also essential to follow the course of the disease and the efficacy of the treatment in affected patients with a standardized follow-up, and to identify early the signs/symptoms of the disease in asymptomatic TTR mutation carriers.This ANMCO position paper on amyloidosis aims to provide the clinical cardiologist with a practical summary of the disease, to accompany the patient with amyloidosis in the various stages of his journey.

Visual Function and Ophthalmological Findings in CHARGE Syndrome: Revision of Literature, Definition of a New Clinical Spectrum and Genotype Phenotype Correlation.

CHARGE syndrome (CS) is a rare genetic disease causing multiple anatomical defects and sensory impairment. Visual function is usually reported by caregivers and has never been described with a structured behavioral assessment. Our primary objective was to describe ocular abnormalities, visual function and genotype-ocular-phenotype correlation in CS. A prospective monocentric cohort study was performed on 14 children with CS carrying pathogenic CHD7 variants. All children underwent ophthalmological evaluation and structured behavioral assessment of visual function. The VISIOCHARGE questionnaire was administered to parents. Colobomas were present in 93% of patients. Genotype-phenotype correlation documented mitigated features in a subset of patients with intronic pathogenic variants predicted to affect transcript processing, and severe features in patients with frameshift/nonsense variants predicting protein truncation at the N-terminus. Abnormal visual function was present in all subjects, with different degrees of impairment. A significant correlation was found between visual function and age at assessment (p-value = 0.025). The present data are the first to characterize visual function in CS patients. They suggest that hypomorphic variants might be associated with milder features, and that visual function appears to be related to age. While studies with larger cohorts are required for confirmation, our data indicate that experience appears to influence everyday use of visual function more than ocular abnormalities do.

Cortical Visual Impairment in CDKL5 Deficiency Disorder.

BACKGROUND: CDKL5 deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene cyclin-dependent kinase-like 5. Cerebral visual impairment (CVI) is frequent in patients with CDD. In addition to being recognized as a specific feature of the pathology, it has been suggested that visual impairment may correlate with neurodevelopmental outcome and epilepsy severity, but no systematic behavioral visual assessment has been performed. The aim of our study was to evaluate clinical and electrophysiological profile of CVI in patients with CDD, to correlate various aspects of visual function to neurodevelopmental and epileptic features. METHODS: The study included all patients with CDD from the National Pathology Registry. All patients underwent neurological examination, a disease-specific functional assessment, structured clinical evaluation of visual functions, including pattern reversal visual evoked potential (VEP), and a detailed monitoring of epileptic features, including video-EEG. RESULTS: All the 11 patients recorded in the CDKL5 national registry, 10 females and one male, age range of 1.5 to 24 years (mean 9, SD 7.7, median 6.5), were enrolled. Visual function is impaired in all patients; in particular, visual fields, visual acuity, contrast sensitivity, and stereopsis were consistently abnormal whereas other aspects, such as fixing and tracking, were relatively preserved. Pattern reversal VEP was abnormal in nearly 80% of our patients. No correlation was found among CVI severity, age, level of psychomotor development, EEG abnormalities, and pathology stages even if an overall less abnormal EEG pattern was more often associated with better visual results. CONCLUSION: In conclusion, CVI can be considered as a major feature of CDD with a diffuse involvement in several behavioral and electrophysiological aspects. Larger cohorts will help to better clarify the possible prognostic role of EEG severity in predicting both visual and developmental abnormalities.