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Two family stories
A 9-year-old apparently healthy girl died suddenly after a running test at school. Resuscitation was futile. On autopsy, the left ventricle was hypertrophied, compatible with hypertrophic cardiomyopathy (HCM). Genetic testing revealed a pathogenic p.Asp175Asn substitution in the α-tropomyosin gene (TPM1), which is the third most common HCM-causing mutation in Finland, accounting for about 6% of all cases. Subsequently, her father, two aunts and grandmother were diagnosed with HCM and the same disease-causing mutation. The father had several risk markers of sudden death, and implantable cardioverter defibrillator was recommended.
In another family, a woman in her 60s was hospitalised due to atrial fibrillation, and echocardiography showed left ventricular hypertrophy. On genetic testing, a rare mutation, p.Thr410Ala of the α-galactosidase A gene (GLA), which causes Fabry disease, was found. In cascade screening, five family members had the same mutation, and symptomatic mutation carriers were started with enzyme replacement therapy.
Why HCM is important: pros and cons of genetic testing in HCM
HCM is arguably the most common cause of sudden cardiac death in the young and athletes. It is the most common monogenic heart disease with mainly autosomal dominant mode of inheritance, with a prevalence of 0.2% in unselected populations.1 However, the prevalence of likely pathogenic sarcomere variants is substantially higher up to 0.6%. HCM is caused primarily by mutations in the genes encoding sarcomere proteins, but disease-causing mutations in non-sarcomeric genes have also been found.1–3 Next generation sequencing techniques including panels of cardiomyopathy-related genes are available in clinical practice at a reasonable price. Current European Society of Cardiology HCM guidelines recommend genetic testing in all patients with HCM.1 Genetic testing provides several advantages. Finding a pathogenic mutation in a patient with HCM confirms the diagnosis, defines the aetiology of the disease and is useful in the differential diagnosis of phenocopies, such as Fabry disease or hereditary transthyretin amyloidosis. Genetic diagnosis …
Contributors JK designed, wrote and edited the article.
Funding This study was funded by the Academy of Finland, Sydäntutkimussäätiö, Kuopion Yliopistollinen Sairaala.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.