A recent paper by researchers in Australia, published this week in Circulation: Cardiovascular Genetics, found more than one rare HCM gene in 4% of patients in a 758 patient sample group.
The researchers found that those patients with multiple rare HCM genes tended to present with HCM at a younger age, were more likely to experience cardiac arrest or death from other causes, and were more likely to require a heart transplant.
In general, few patients have multiples of mutations commonly associated with HCM. See this Canadian study from April of this year which found that multiple mutations were less prevalent and harmful than previously thought.
According to researchers at the University of Michigan, family members of HCM patients who have tested negative for genes associated with HCM and without a family history of HCM will usually be found to be free of HCM during routine family screening. And, in accordance a recent Australian study, relatives of these patients may be able to benefit from less rigorous screening protocols.
Patients with a known sarcomere mutation appear to have a different clinical profile, according to the researchers: they have more hypertrophy; they are younger when diagnosed; they have a higher risk for adverse events; and they are more likely to have a family history for the condition.
In contrast, when the initial diagnosis is made in a patient who is 50 or older with no known genetic mutations, a negative family history, and sigmoidal septal pattern hypertrophy, reduced family screenings may be appropriate and less burdensome. In addition, hypertension, large family size with no other affected family members, less severe hypertrophy, and lack of life-threatening complications related to HCM may provide additional comfort to families of newly diagnosed HCM patients.
The reduced protocol would consist of a single screening of adult family members, with the caveat that if and when any additional family additional member is found to have HCM, a more traditional screening protocol be instituted.
(Note that standard screening guidelines recommend screening of all first-degree family members of patients beginning with adolescence, repeated annually through the end of adolescent growth, and repeated every 3 – 5 years for life.)
When a patient is the only person in the family ever diagnosed with HCM, s/he will often wonder whether their disease is, in fact, genetic. S/he will also wonder whether it will be necessary for all first degree relatives to undergo serial screenings for the rest of their lives.
In answer to this concern, Australian researchers have recently identified a subset of HCM patients who appear to have a non-familial form of the disease and whose relatives may be candidates for less stringent screening protocols.
The study, just published in Circulation: Cardiovascular Genetics by Dr. Jodie Ingles and Dr. Chris Semsarian, found that this group, having neither genetic mutation associated with HCM nor family history of HCM, comprises approximately 40% of all HCM patients. Non-familial HCM patients are more likely to be older when diagnosed, and they often present with non-asymmetric hypertrophy and hypertension. And, these HCM patients appear to have a more favorable clinical course, with a better track record of survival from major cardiovascular events.
The researchers point out that by sorting patients into more distinct subgroups, doctors will be able to provide more personalized and evidence-based care to patients and their families. In particular, their recommendation is that first-degree relatives of non-familial HCM patients need only be screened one or more times in adulthood. Less frequent follow up surveillance is also suggested, in contrast with the more intensive screening guidelines recommended for family members of patients with familial HCM.