Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity.

Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations.

Who Pays? Coverage Challenges for Cardiovascular Genetic Testing in U.S. Patients.

Inherited cardiovascular (CV) conditions are common, and comprehensive care of affected families often involves genetic testing. When the clinical presentations of these conditions overlap, genetic testing may clarify diagnoses, etiologies, and treatments in symptomatic individuals and facilitate the identification of asymptomatic, at-risk relatives, allowing for often life-saving preventative care. Although some professional society guidelines on inherited cardiac conditions include genetic testing recommendations, they quickly become outdated owing to the rapid expansion and use of such testing.

Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that can be found in both children and adults and is associated with many causative mutations. In children who are not the index case of HCM in their families, current recommendations call only for targeted genetic testing for familial mutations. However, clinical experience suggests that de novo mutations are possible, as are mutations inherited from apparently an unaffected parent.

Novel and highly lethal NKX2.5 missense mutation in a family with sudden death and ventricular arrhythmia.

To date, several disease-related mutations in NKX2-5, a cardiac-specific homeobox gene, have been documented in patients with a variety of congenital heart diseases (CHDs). The most commonly reported phenotypes are secundum atrial septal defect (ASD) and atrioventricular conduction disease (AVCD). Reports of sudden cardiac death (SCD) have been attributed to progressive conduction disease preventable with pacemaker therapy.

Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture.

Background: Herpesviruses are ubiquitous pathogens that infect and cause recurrent disease in multiple animal species. Feline herpesvirus-1 (FHV-1), a member of the alphaherpesvirus family, causes respiratory illness and conjunctivitis, and approximately 80% of domestic cats are latently infected. Oral administration of famciclovir or topical application of cidofovir has been shown in masked, placebo-controlled prospective trials to reduce clinical signs and viral shedding in experimentally inoculated cats.

Silicone-acyclovir controlled release devices suppress primary herpes simplex virus-2 and varicella zoster virus infections in vitro.

Following initial infection, herpesviruses retreat into a permanent latent state with periodic reactivation resulting in an enhanced likelihood of transmission and clinical disease. The nucleoside analogue acyclovir reduces clinical symptoms of the three human alpha herpesviruses, HSV-1, HSV-2, and VZV. Long-term administration of acyclovir (ACV) can reduce the frequency and severity of reactivation, but its low bioavailability and short half-life require a daily drug regimen.

Genetic evaluation of familial cardiomyopathy.

Hereditary forms of hypertrophic, dilated, restrictive, and right ventricular cardiomyopathies are frequently seen. Patterns of inheritance include autosomal dominant, autosomal recessive, X-linked, and matrilinear. Recognition of the mode of inheritance facilitates proper clinical screening of family members in subsequent generations.