Genetics and family screening

Genetics

Hypertrophic cardiomyopathy is often genetic and therefore familiar. Genes are portions of DNA, a substance contained in all the cells of our body and that cells use as an "alphabet" to build all the proteins (substances that serve for the structure and cellular function) of our body. A mutation is an error in one of these genes, which can either be inherited from the parents or occur for the first time in affected subjects; in both cases the altered gene can be transmitted to the children with a probability of 50%. An altered gene corresponds to an altered protein, which in some cases can give rise to a disease. Since cells of different tissues use different genes, mutations (=errors) in a particular gene generally involve a particular tissue. Hypertrophic cardiomyopathy is almost always caused by mutations in genes that are used to build proteins contained in heart tissue. The main genes responsible are genes linked to: myosin heavy chain beta, myosin-binding protein C, and cardiac troponin T (but there are many others).

Patients who have the same mutation in the same gene may have different variability in the degree of severity of the disease, and this is also true for affected subjects within the same family (so-called variable expressivity). Moreover, not all patients who have the mutation develop the disease (so-called incomplete penetration). Typically, hypertrophic cardiomyopathy occurs during adolescence, but can occur at any age, from birth to advanced adult life.

It is possible, using a blood sample, to search for the mutation responsible for the disease and our center has the latest technology ("next generation sequencing") for genetic analysis.

Family Screening

Family screening is recommended in all cases of suspected or confirmed hypertrophic cardiomyopathy. All first-degree relatives (children/brothers or sisters/parents) or second/third-degree relatives etc. are usually evaluated if they are symptomatic, or if there is a suspicion of disease. Basic screening includes cardiological examination, ECG and echocardiogram; the centre may then ask for further testing, if appropriate. It is recommended that screening be performed in centres with expertise in the management of cardiomyopathies, as initial clinical and instrumental pictures of the disease may be blurred and difficult to diagnose. There are no precise rules on when to start screening in young children, but usually we recommend a first evaluation at 5-6 years (or first depending on the symptoms/family history/discretion of the doctor) and then at 10-12 years, every year or six months during the adolescent phase (up to 18-20 years) and then every 3-5 years in the adulthood (or at the onset of symptoms); these time-frames are approximate and may vary depending on family history or clinical/instrumental variables detected by the Cardiologist. Screening is repeated over time, because the disease can develop at any age.