Hypertrophic cardiomyopathy (HCM): inherited thickened heart muscle

In hypertrophic cardiomyopathy the muscular wall of the heart thickens, most often the left ventricle, the main pumping chamber, and sometimes the septum between the two sides. The British Heart Foundation explains that this can make the muscle stiff and the heart less able to pump blood. How thick the muscle gets, and how much of it is affected, differs for everyone.

Most people have no symptoms or feel stable throughout life. Where symptoms do occur the British Heart Foundation lists chest pain, light-headedness and fainting, palpitations, breathlessness, tiredness and swelling of the legs, feet, ankles and abdomen. Some people find symptoms worsen in later life. HCM can lead to abnormal rhythms such as atrial fibrillation or heart block, to a leaky mitral valve, to endocarditis, and rarely to a life-threatening rhythm that can cause cardiac arrest. This is why identifying who has HCM matters even if they feel well.

• Fainting, especially during or after exercise, is treated by the NHS Genomics Education Programme as a possible marker of higher risk that should be escalated.

• Obstructive HCM means the thickening reduces blood flow out of the heart; non-obstructive means it does not (British Heart Foundation).

HCM is most commonly caused by changes in genes that encode the proteins of the sarcomere, the contractile machinery of heart muscle cells. The NHS Genomics Education Programme lists MYBPC3 and MYH7 as each accounting for about 40% of cases where a variant is found, with TNNT2 (7% to 15%), TNNI3 (about 5%), TPM1 (about 3%) and several others contributing smaller shares.

Other inherited conditions can mimic HCM. The programme names transthyretin amyloidosis, Fabry disease, Noonan syndrome and its related conditions, and PRKAG2 and LAMP2 disorders as phenocopies. They matter because their course and treatment are different, so genomic testing may be used when an unusual form is suspected.

HCM usually follows an autosomal dominant pattern with variable expressivity and age-related penetrance. In everyday terms, a parent with the variant has a 50% chance of passing it to each child, but whether and when the heart thickens varies from person to person. The British Heart Foundation states the chance for a child of someone with HCM as 50%.

The NHS Genomics Education Programme stresses that someone who carries a harmful variant but has no thickening at the time of testing may develop HCM later in life, and can still pass the variant on to children. It illustrates this with the figure that nearly half of adults under the age of 50 with a likely pathogenic MYBPC3 variant do not have cardiac hypertrophy. For this reason HCM can sometimes appear to skip a generation, and a normal heart scan in a young relative with the family variant is not the end of follow-up.

The British Heart Foundation lists the usual tests: a physical assessment, an electrocardiogram, an echocardiogram (ultrasound of the heart), an exercise test and a cardiac MRI. Genetic testing is not usually needed to diagnose HCM. The NHS Genomics Education Programme says its main purpose is to enable presymptomatic diagnosis in relatives after a diagnosis in the family.

If a faulty gene is found, a clinician may ask to talk to close relatives. The British Heart Foundation recommends that a parent, brother, sister or child of someone with HCM is seen at a specialist inherited heart conditions clinic to talk about genetic testing and heart screening. A positive family gene lets relatives have a single targeted test. If the original patient has no variant found, relatives are still advised to have clinical heart screening, because a negative test in the first person does not show that HCM is not inherited.

There is currently no cure, but treatment controls symptoms and aims to prevent complications. The British Heart Foundation says treatment depends on how the heart is affected and may include diuretics, beta blockers and cardiac myosin inhibitors, an implantable cardioverter defibrillator for those at risk of a dangerous rhythm, a pacemaker, catheter ablation for some arrhythmias, septal myectomy surgery to remove part of the thickened wall, or an LVAD to help the heart pump.

The NHS Genomics Education Programme says management is multidisciplinary and should involve a specialist inherited cardiac conditions service. It addresses symptoms, the risk of sudden arrhythmic death, blood clots and heart failure, as well as implications for lifestyle, sport, pregnancy, anaesthesia and work.

Day-to-day, the British Heart Foundation says most people can work, though not strenuous manual jobs, can enjoy most activities though not some competitive sports or very high-intensity exercise, and can usually keep driving, though HGV and bus licences may be affected. It also says sex is as safe as other physical activity at a comfortable level.