Aortic Root Dilation and Genotype Associations in Phelan-McDermid Syndrome.

Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the SHANK3 gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (p = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (p = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD.

Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

The Utility of Virtual Home Visits to Reduce Asthma Burden in Low-Income Black Communities in Louisiana During the COVID-19 Pandemic.

OBJECTIVES: The Louisiana Department of Health identified a need for greater outreach in low-income Black communities that addressed environmental asthma triggers. We piloted an asthma virtual home visit (VHV) program and evaluated its reach and ability to promote asthma self-management strategies in communities with a high prevalence of poorly controlled asthma. METHODS: Participants from Louisiana were continuously recruited into the VHV program starting in March 2021 and provided with asthma education materials. Participants reporting poorly controlled asthma and environmental triggers were also offered 3 VHVs with a respiratory therapist. All participants were asked to complete a preintervention and postintervention knowledge test, an Asthma Control Test (ACT) (maximum score = 25; scores ≤19 indicate poorly controlled asthma), and a final survey that assessed perceptions about asthma management and reduction of environmental triggers. RESULTS: As of October 2022, 147 participants were enrolled in the program, and 52 had consented to and received ≥1 VHV. Forty VHV recipients (77%) were aged <18 years, 40 (77%) were Black people, and 46 (88%) were from families with extremely low or low incomes. Asthma symptoms improved across all participants, with a median increase of 2.4 points on the ACT. Knowledge tests revealed that 86% of participants learned about ≥1 new asthma trigger; a larger percentage of VHV recipients than nonrecipients (68% vs 36%) had an improved knowledge test score postintervention. Compared with preintervention, about three-quarters of participants reported feeling more empowered to self-manage their asthma and a significant improvement in their quality of life postintervention. CONCLUSIONS: The program provided virtual asthma education to communities with a high burden of asthma and improved asthma outcomes for participants. Similar virtual models can be used to promote health equity, especially in areas with limited access to health care.

Gait Abnormalities in Children with Phelan-McDermid Syndrome.

Background: Phelan-McDermid syndrome is a genetic disorder caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.3 and is characterized by autism spectrum disorder, intellectual disability, speech and language abnormalities, hypotonia, and mild dysmorphic features. Early literature in Phelan-McDermid syndrome did not include gait abnormalities as part of the syndrome although recent prospective studies report that the prevalence of gait abnormalities ranges from 55% to 94%. We compared gait abnormalities in individuals with Phelan-McDermid syndrome, idiopathic autism spectrum disorder, and typically developing controls, and explored associations between gait abnormalities, autism spectrum disorder, and intellectual functioning. Method: The study cohort consists of 67 participants between the ages of 3 and 18 years, divided into 3 groups: Phelan-McDermid syndrome (n = 46), idiopathic autism spectrum disorder (n = 11), and typically developing controls (n = 10). Gait was recorded using a video camera and scored across 26 gait features using a "Gait Clinical Observations scale" designed specifically for this study. Results: Gait abnormalities were significantly higher in the Phelan-McDermid syndrome group as compared to idiopathic autism spectrum disorder or typically developing controls. The number of gait abnormalities across groups was also significantly correlated with Intellectual Quotient/Developmental Quotient (IQ/DQ). In analysis of covariance including IQ/DQ, the effect of group was not significant, but the effect of IQ/DQ was significant. Conclusions: Overall differences in gait abnormalities were determined by the degree of intellectual disability, which was significantly higher in Phelan-McDermid syndrome.

Identifying Louisiana communities at the crossroads of environmental and social vulnerability, COVID-19, and asthma.

The COVID-19 pandemic has disproportionately affected the socially and environmentally vulnerable, including through indirect effects on other health conditions. Asthma is one such condition, which may be exacerbated by both prolonged adverse in-home exposures if quarantining in unhealthy homes and prolonged outdoor exposures if the ambient air quality is unhealthy or hazardous. As both are often the case in Environmental Justice (EJ) communities, here we have analyzed data at the census tract (CT) level for Louisiana to assess any correlation between social and environmental vulnerability, and health issues like COVID-19 and asthma. Higher Social Vulnerability Index (SVI), Particulate Matter less than 2.5 µm in diameter (PM2.5) and Ozone levels were associated with higher rates of cumulative COVID-19 incidence at various time points during the pandemic, as well as higher average annual asthma hospitalization rates and estimated asthma prevalence. Further, cumulative COVID-19 incidence during the first three months of the pandemic was moderately correlated with both asthma hospitalizations and estimated prevalence, suggesting similar underlying factors may be affecting both conditions. Additionally, 137 CTs were identified where social and environmental vulnerabilities co-existed, of which 75 (55%) had high estimated prevalence of asthma. These areas are likely to benefit from asthma outreach that considers both social and environmental risk factors. Fifteen out of the 137 CTs (11%) not only had higher estimated prevalence of asthma but also a high burden of COVID-19. Further research in these areas may help to elucidate any common social determinants of health that underlie both asthma and COVID-19 burdens, as well as better clarify the possible role of the environment as related to the COVID-19 burden in Louisiana.