The phenotypic presentation of adult individuals with SLC6A1-related neurodevelopmental disorders

Introduction: SLC6A1 is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. SLC6A1-neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population. Method: Here, we sought to describe patients with SLC6A1 variants and age above 18 years through the ascertainment of published and unpublished patients. Unpublished patients were ascertained through international collaborations, while previously published patients were collected through a literature search. Results: A total of 15 adult patients with SLC6A1 variants were included. 9/13 patients had moderate to severe ID (data not available in two). Epilepsy was prevalent (11/15) with seizure types such as absence, myoclonic, atonic, and tonic–clonic seizures. Epilepsy was refractory in 7/11, while four patients were seizure free with lamotrigine, valproate, or lamotrigine in combination with valproate. Language development was severely impaired in five patients. Behavioral disorders were reported in and mainly consisted of autism spectrum disorders and aggressive behavior. Schizophrenia was not reported in any of the patients. Discussion: The phenotype displayed in the adult patients presented here resembled that of the pediatric cohort with ID, epilepsy, and behavioral disturbances, indicating that the phenotype of SLC6A1-NDD is consistent over time. Seizures were refractory in &gt;60% of the patients with epilepsy, indicating the lack of targeted treatment in SLC6A1-NDDs. With increased focus on repurposing drugs and on the development of new treatments, hope is that the outlook reflected here will change over time. ID appeared to be more severe in the adult patients, albeit this might reflect a recruitment bias, where only patients seen in specialized centers were included or it might be a feature of the natural history of SLC6A1-NDDs. This issue warrants to be explored in further studies in larger cohorts.</p

The phenotypic presentation of adult individuals with SLC6A1-related neurodevelopmental disorders

IntroductionSLC6A1 is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. SLC6A1-neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population.MethodHere, we sought to describe patients with SLC6A1 variants and age above 18 years through the ascertainment of published and unpublished patients. Unpublished patients were ascertained through international collaborations, while previously published patients were collected through a literature search.ResultsA total of 15 adult patients with SLC6A1 variants were included. 9/13 patients had moderate to severe ID (data not available in two). Epilepsy was prevalent (11/15) with seizure types such as absence, myoclonic, atonic, and tonic–clonic seizures. Epilepsy was refractory in 7/11, while four patients were seizure free with lamotrigine, valproate, or lamotrigine in combination with valproate. Language development was severely impaired in five patients. Behavioral disorders were reported in and mainly consisted of autism spectrum disorders and aggressive behavior. Schizophrenia was not reported in any of the patients.DiscussionThe phenotype displayed in the adult patients presented here resembled that of the pediatric cohort with ID, epilepsy, and behavioral disturbances, indicating that the phenotype of SLC6A1-NDD is consistent over time. Seizures were refractory in &gt;60% of the patients with epilepsy, indicating the lack of targeted treatment in SLC6A1-NDDs. With increased focus on repurposing drugs and on the development of new treatments, hope is that the outlook reflected here will change over time. ID appeared to be more severe in the adult patients, albeit this might reflect a recruitment bias, where only patients seen in specialized centers were included or it might be a feature of the natural history of SLC6A1-NDDs. This issue warrants to be explored in further studies in larger cohorts

New Evidence on BEST1 Genetic Variant Identified in a Patient with Best Vitelliform Macular Dystrophy Phenotype

Best Disease (BD), also known as Best Vitelliform Macular Dystrophy (BVMD), represents an inherited autosomal dominant macular dystrophy with a juvenile age of onset [1]. It is a phenotypically heterogeneous, bilateral condition that affects the retina and Retinal Pigment Epithelium (RPE) caused by pathogenic variants in the BEST1 gene located on chromosome 11q12-13 [2,3]. Typical fundus findings in BD are egg yolk-like, round or oval, lesions seen in the macula, and affected eyes may demonstrate various clinical stages, ranging from the previtelliform stage to Choroidal Neovascularization (CNV) [4]. The macular appearance in all stages is deceptive, as most patients maintain relatively good visual acuity throughout the course of the disease. Patients commonly experience visual compromise in early adulthood, although the age of onset can range from childhood to late adulthood [3] and most patients with BD maintain good vision in at least one eye. The presence of subretinal fluid or CNV has been associated with a poorer visual prognosis [4]. In this case report, we describe a patient with clinical features suggestive of Best disease. We discuss the differential diagnosis and we present the multimodal imaging of the retina used for both the diagnosis and follow up. We also report a genetic study that demonstrates more evidence on a novel genetic variant in the BEST1 gene. The same genetic mutation has been recently reported as a novel variant in a single patient with BVMD [5].</jats:p

Aortic stiffness and distensibility in elite athletes: impact of discipline and gender

Abstract Background Aortic remodeling in athletes is variable among sports disciplines with more ascending aorta (Asc Ao) dilatation in endurance (EAs) as compared to power athletes (PAs). Nevertheless, the impact of this differential remodeling on the Asc Ao functional properties is not well established. The aim of this study was to assess the distensibility and stiffness of the ascending aorta in endurance and power elite athletes in order to evaluate if this aortic remodeling implies functional changes. Methods 119 elite athletes (61 EA and 58 PA, 49% female sex, mean age: 18.7±7.1 years) underwent standardized pre-participation screening with 12 lead ECG, transthoracic echocardiography and maximum stress test. Asc Ao diameter was measured from parasternal long axis views in 2D echocardiography. The aortic distensibility index (ADi) was calculated as 2 × (systolic Asc Ao diameter − diastolic Asc Ao diameter) / (diastolic Asc Ao diameter) × (pulse pressure) (cm–2 dyn–1 10–6). Aortic stiffness (AS) index was defined as Ln (systolic blood pressure/diastolic blood pressure) / (systolic Asc Ao diameter − diastolic Asc Ao diameter)/diastolic proximal Asc Ao diameter. Results Globally, EA presented larger AscAO, both in absolute and indexed values, than PA (28±3.0 vs 26±3.0cm, p&amp;lt;0.001 and 16.4±1.5 vs 15.7±1.9cm, p&amp;lt;0.05, while were no differences in AS or ADi) (Figure 1A). Nevertheless, ADi in male EAs was higher than in male PAs (ADi: 4.3±1.7 vs 3.2±1.3 cm2/dyn/10–6, p&amp;lt;0.05) and AS was lower (AS: 4.7±1.7 vs 6.3±3.8, P&amp;lt;0.005) (Figure 1B and 1C). Female athletes presented higher ADi (ADi: 4.7±1.9 vs 4.0±1.6 cm, p&amp;lt;0.05) and a trend towards lower AS (4.8±2.9 vs 5.1±2.6, p: 0.4) than male athletes. There were no differences in AS or ADi between female EAs and PAs. Conclusion Male EAs showed an increased aortic distensibility with lower stiffness as compared to that observed in male PAs. This difference was not observed in female EAs and PAs, potentially due to better baseline distensibility with less room for improvement with endurance training. Funding Acknowledgement Type of funding source: None </jats:sec