Diagnostic Yield of Exome Sequencing in Pediatric Cardiomyopathy.

OBJECTIVE: To assess the diagnostic yield of exome sequencing (ES) in pediatric cardiomyopathy. STUDY DESIGN: A single-institution, retrospective chart review of 91 patients with pediatric cardiomyopathy was performed. While pediatric cardiomyopathy is often genetic in nature, no genetic test is recommended as standard of care. All our patients were diagnosed with cardiomyopathy and evaluated by a medical geneticist between January 2010 through September 2022. Demographic information and clinical data were abstracted. RESULTS: Of 91 patients with pediatric cardiomyopathy, 36 (39.6%) received a diagnosis by ES. Twenty-two (61.1%) of these diagnoses would have been missed on cardiac multigene panel testing. The diagnostic yield for cardiomyopathy presenting under 1 year of age was 38.3%, while the yield for patients over 1 year of age was 41.9%. CONCLUSIONS: ES has a high diagnostic yield in pediatric cardiomyopathy compared with a gene panel. Over 60% of patients with diagnosis by ES would not have received their molecular genetic diagnosis if only multigene panel testing was sent. Diagnostic yield did not vary significantly between the subtypes of cardiomyopathy and patient age groups, highlighting the likely clinical utility of ES for all pediatric cardiomyopathy patients.

Trends in coverage and reimbursement for reproductive genetic counseling in New Jersey by multiple payers from 2010 to 2018.

Lack of consistent insurance coverage for genetic counseling services billed under Current Procedural Terminology (CPT) code 96040 creates a barrier for access to this service. This retrospective study examined coverage and reimbursement for reproductive genetic counseling encounters billed under CPT code 96040 as a professional fee over an eight-year period at Rutgers Robert Wood Johnson Medical School, a regional perinatal center in New Jersey, a state requiring licensure. Descriptive statistics were tabulated to assess the disparity between Medicare/Medicaid, Managed Care Medicaid, and commercial insurance payers, including how often encounters were covered and if reimbursed, at what percentage of the amount billed. A comparison of individual plan types (Health Maintenance Organization, Point of Service, and Preferred Provider Organization) was carried out. Overall trends in reimbursement were assessed across payers. The study found 61% of 60-min encounters billed to Medicare/Medicaid, Managed Care Medicaid, and commercial insurance payers received coverage. Of all covered 60-min encounters billed to Managed Care Medicaid and commercial insurance payers, an average of 36% of the amount billed was reimbursed. Medicare/Medicaid encounters were never reimbursed. Commercial insurance covered 65% of encounters billed but this varied between payers. Across all payers, an overall downward trend of reimbursement was demonstrated over the eight-year period. Lack of consistent service coverage creates a barrier and patients cannot universally access genetic counseling services. Steps to improve coverage need to include passing of legislation, notably the next bill to replace the former H.R. 3235, 'Access to Genetic Counselor Services Act of 2019' and provisions within third-party payers that allow for credentialing of genetic counseling providers.

Empiric Recurrence Risk Estimates for Chronic Tic Disorders: Implications for Genetic Counseling.

Background: Tourette disorder (TD) and other chronic tic disorders are neurodevelopmental/neuropsychiatric disorders characterized by motor and/or vocal tics. Family studies indicate that TD strongly aggregates within families and that other chronic tic disorders are biologically related such that studies typically combine them into any chronic tic disorder (CTD). Because of stigma, bullying, and comorbidity with other neuropsychiatric disorders, CTDs can severely impact the quality of life of individuals with these disorders. Objectives: The genetic architecture of CTDs is complex and heterogeneous, involving a myriad of genetic variants. Thus, providing familial recurrence risks is based on empirical recurrence risk estimates rather than genetic testing. Because empiric recurrence risks for CTDs have not been published, the purpose of this study is to calculate and report these recurrence risks estimates. Methods: Based on population prevalence and increased risk to different relatives from a large population-based family study, we calculated the empiric recurrent risk estimate for each relative type (full sibling, parents, offspring, all first-degree, and all second-degree). Results: The recurrence risk estimate for CTDs in first-degree relatives is 29.9% [95% confidence interval (CI) = 23.2-38.5%]. The risk is higher in males, 33.7% (95% CI = 26.2-43.3%), than females, 24.3% (95% CI = 18.9-31.3%). Conclusions: Given the complex, heterogeneous genetic architecture of CTDs, individuals concerned about recurrence risk should be referred to genetic counseling. Such counseling should include discussion of the derivation and limitations of these empiric recurrence risk estimates, including the upper and lower limits of the range of risk.

Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty.

OBJECTIVE: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. DESIGN: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. METHODS: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH > or = 7 IU/l, advanced bone age > 1 year, enlarged uterus (> or = 36 mm) and testosterone level > or = 0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. RESULTS: GnRH-stimulated peak LH < or = 3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. CONCLUSIONS: The triptorelin 3-month depot efficiently suppresses the pituitary-gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.