講演情報
[OE6-1]Family cascade testing in 54,407 patients undergoing cardiomyopathy and arrhythmia genetic testing
○Aradhya Swaroop, Callis Thomas, Morales Ana, Mitchell Asia, Poll Sarah, Garcia John, McKnight Dianalee, Mortez Chad, Vatta Matteo, Nussbaum Robert (Invitae Inc., San Francisco, USA)
INTRODUCTION
Cardiomyopathies (CM) and arrhythmias (ARRH) affect ~1 in 300-400 and can present with advanced disease. AHA recommends genetic testing in probands and at-risk relatives. We describe outcomes in individuals referred for genetic testing.
METHODS
Probands had one or more CM, CM-ARRH, or ARRH gene panel tests. Relatives had cascade testing. Positive results were defined as a P/LP variant for an autosomal dominant condition, two P/LP for a recessive condition, or one P/LP in a male or two P/LP in a female for an X-linked condition.
RESULTS
Across 7 years, 54,407 probands had testing, including 18,295 with CM-ARRH sponsored testing and 2,244 postmortem samples. Positive results were reported in 19% individuals, among which 11.5% were in a gene related to a syndromic disorder. Most positive results were in non-syndromic CM, CM-ARRH and Long QT syndrome genes. Other results with management implications included cardiac amyloidosis, rasopathy, Fabry disease, and Duchenne muscular dystrophy. The proportion of positive results was the same for CM and CM-ARRH by proband sex and age. Among those tested for ARRH, males and probands < 18 yo were more likely to be positive. Cascade testing was pursued in 4,302 (41.6%) families (35.9% positive). Families with child probands had cascade testing more often.
CONCLUSIONS
19% of probands had a positive result, but cascade testing occurred in only 41.6% of families, and more frequently in families with child probands. Most at-risk relatives do not receive genetic testing. We highlight the need for research to improve the uptake of cascade testing.
Cardiomyopathies (CM) and arrhythmias (ARRH) affect ~1 in 300-400 and can present with advanced disease. AHA recommends genetic testing in probands and at-risk relatives. We describe outcomes in individuals referred for genetic testing.
METHODS
Probands had one or more CM, CM-ARRH, or ARRH gene panel tests. Relatives had cascade testing. Positive results were defined as a P/LP variant for an autosomal dominant condition, two P/LP for a recessive condition, or one P/LP in a male or two P/LP in a female for an X-linked condition.
RESULTS
Across 7 years, 54,407 probands had testing, including 18,295 with CM-ARRH sponsored testing and 2,244 postmortem samples. Positive results were reported in 19% individuals, among which 11.5% were in a gene related to a syndromic disorder. Most positive results were in non-syndromic CM, CM-ARRH and Long QT syndrome genes. Other results with management implications included cardiac amyloidosis, rasopathy, Fabry disease, and Duchenne muscular dystrophy. The proportion of positive results was the same for CM and CM-ARRH by proband sex and age. Among those tested for ARRH, males and probands < 18 yo were more likely to be positive. Cascade testing was pursued in 4,302 (41.6%) families (35.9% positive). Families with child probands had cascade testing more often.
CONCLUSIONS
19% of probands had a positive result, but cascade testing occurred in only 41.6% of families, and more frequently in families with child probands. Most at-risk relatives do not receive genetic testing. We highlight the need for research to improve the uptake of cascade testing.