A rapid scoring tool to assess mutation probability in patients with inherited cardiac disorders

Eur J Med Genet. 2018 Feb;61(2):61-67. doi: 10.1016/j.ejmg.2017.10.020. Epub 2017 Nov 2.


Aims: To explore clinical features and relationship with positive mutation ascertainment in inherited heart diseases in order to develop a clinical tool to assist identification of individuals in whom to offer genetic testing. A clinical tool that increases pre test probability of mutation detection would have the benefits of improving patient counselling, prioritising cases for MPS and allowing equity in decision making.

Methods and results: Consecutive MPS mutation detection testing cases were identified (September 2014 - December 2015, n = 126). Cases were scored for the presence of pre-determined clinical and family history variables, blinded to MPS results. Subsequent unblinding allowed ascertainment of the odds ratio (OR) between these clinical variables and positive mutation detection. A clinical tool was developed and variables with higher OR association were given a higher weighting. The mean score in the cohort was 3.94: mutation positive subgroup 4.74, and mutation negative subgroup: 3.49 (t-test, p < 0.0001). The clinical tool was validated in a cohort of 40 patients. There was a strong linear correlation between increasing clinical tool score and probability of detecting a mutation (r2 = 0.88).

Conclusion: Clinical information on probands and their family history allows identification of individuals with a greater chance of positive mutation detection. This improves pre test counselling, allows equitable identification of individuals in whom to offer cardiac genetic testing and can be calibrated to a predictable ratio of positive mutation and missed opportunity cases for individual health services.

Keywords: Aortic diseases; Arrhythmias; Cardiomyopathy; Cost-effectiveness; Genetics; Sudden cardiac death.

MeSH terms

  • Adult
  • Female
  • Genetic Counseling / methods
  • Genetic Testing / methods*
  • Genetic Testing / standards
  • Heart Diseases / diagnosis
  • Heart Diseases / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Probability