A qualitative assessment of parental experiences with false-positive newborn screening for Krabbe disease.

Numerous US states have implemented newborn screening for Krabbe disease (Krabbe NBS) as a result of legislative state mandates. While healthcare provider opinions toward Krabbe NBS have been documented, few studies have explored parental experiences and opinions regarding Krabbe NBS. Eleven families, who received a false-positive Krabbe NBS result and received genetic counseling at an institution in central Ohio, were consented to participate in semistructured interviews. Interviews explored parents' experiences throughout the NBS process and ascertained their opinions regarding Krabbe NBS. Three major themes emerged from thematic analysis: (1) improved understanding of the NBS process from a parent perspective, (2) the role of healthcare provider communication, and (3) the value of Krabbe NBS. Parents saw value in Krabbe NBS, despite many disclosing emotional distress and uncertainty throughout the NBS process. Parent experiences throughout the NBS process varied widely. Due to the expressed emotional distress, further research assessing effective communication during the NBS process is warranted. The researchers suggest additional NBS education for non-genetics healthcare providers (i.e., nurses or primary care physicians) and further participation of genetic counselors in the NBS process may benefit families with a positive Krabbe NBS result.

Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.

BACKGROUND: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted. METHODS: An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated. RESULTS: Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%; ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence. CONCLUSIONS: In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.