Definition and clinical variability of SHANK3-related Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is an infrequently described syndrome that presents with a disturbed development, neurological and psychiatric characteristics, and sometimes other comorbidities. As part of the development of European medical guidelines we studied the definition, phenotype, genotype-phenotype characteristics, and natural history of the syndrome. The number of confirmed diagnoses of PMS in different European countries was also assessed and it could be concluded that PMS is underdiagnosed. The incidence of PMS in European countries is estimated to be at least 1 in 30,000. Next generation sequencing, including analysis of copy number variations, as first tier in diagnostics of individuals with intellectual disability will likely yield a larger number of individuals with PMS than presently known. A definition of PMS by its phenotype is at the present not possible, and therefore PMS-SHANK3 related is defined by the presence of SHANK3 haploinsufficiency, either by a deletion involving region 22q13.2-33 or a pathogenic/likely pathogenic variant in SHANK3. In summarizing the phenotype, we subdivided it into that of individuals with a 22q13 deletion and that of those with a pathogenic/likely pathogenic SHANK3 variant. The phenotype of individuals with PMS is variable, depending in part on the deletion size or whether only a variant of SHANK3 is present. The core phenotype in the domains development, neurology, and senses are similar in those with deletions and SHANK3 variants, but individuals with a SHANK3 variant more often are reported to have behavioural disorders and less often urogenital malformations and lymphedema. The behavioural disorders may, however, be a less outstanding feature in individuals with deletions accompanied by more severe intellectual disability. Data available on the natural history are limited. Results of clinical trials using IGF-1, intranasal insulin, and oxytocin are available, other trials are in progress. The present guidelines for PMS aim at offering tools to caregivers and families to provide optimal care to individuals with PMS.

Rapid Implementation of Telegenetic Counseling in the COVID-19 and Swedish Healthcare Context: A Feasibility Study

This study reports the process and preliminary findings of rapid implementation of telegenetic counseling in the context of Swedish healthcare and COVID-19 pandemic, from both a patient and a provider perspective. Fourty-nine patients and 6 healthcare professionals were included in this feasibility study of telegenetic counseling in a regional Department of Clinical Genetics in Sweden. Telegenetic counseling is here defined as providing genetic counseling to patients by video (n = 30) or telephone (n = 19) appointments. Four specific feasibility aspects were considered: acceptability, demand, implementation, and preliminary efficacy. Several measures were used including the Genetic Counseling Outcome Scale 24 (collected pre- and post-counseling);the Telehealth Usability Questionnaire;a short study specific evaluation and Visiba Care evaluations, all collected post-counseling. The measures were analyzed with descriptive statistics and the preliminary results show a high level of acceptance and demand, from both patients and providers. Results also indicate successful initial implementation in the regional Department of Clinical Genetics and preliminary efficacy, as shown by significant clinically important improvement in patients' empowerment levels.

Rapid Implementation of Telegenetic Counseling in the COVID-19 and Swedish Healthcare Context: A Feasibility Study.

This study reports the process and preliminary findings of rapid implementation of telegenetic counseling in the context of Swedish healthcare and COVID-19 pandemic, from both a patient and a provider perspective. Fourty-nine patients and 6 healthcare professionals were included in this feasibility study of telegenetic counseling in a regional Department of Clinical Genetics in Sweden. Telegenetic counseling is here defined as providing genetic counseling to patients by video (n = 30) or telephone (n = 19) appointments. Four specific feasibility aspects were considered: acceptability, demand, implementation, and preliminary efficacy. Several measures were used including the Genetic Counseling Outcome Scale 24 (collected pre- and post-counseling); the Telehealth Usability Questionnaire; a short study specific evaluation and Visiba Care evaluations, all collected post-counseling. The measures were analyzed with descriptive statistics and the preliminary results show a high level of acceptance and demand, from both patients and providers. Results also indicate successful initial implementation in the regional Department of Clinical Genetics and preliminary efficacy, as shown by significant clinically important improvement in patients' empowerment levels.