Familial Cardiomyopathies ( Fc )

5585 Words23 Pages
Background: Familial Cardiomyopathies (FC) are a collection of cardiac diseases that vary vastly genetically, and pathologically (1, 2). Hypertrophic cardiomyopathy (HCM) is the most common form of FC (2). HCM is diagnosed often with left ventricular hypertrophy without a noticeable increase in external load and smaller ventricular cavity, but with a preserved ejection fraction (3). That is, the percent of blood leaving the left ventricle (5) does not change. Other pathologies include interstitial fibrosis, thickening of the media in intramural arteries, and myocytes disarray greater than 5%; which is a hallmark of HCM (4). HCM shows variability in its penetrance, from a patient with no symptoms, to having sudden cardiac death (SCD)…show more content…
As a result, many patients that do not fit standard diagnostic criteria may in fact have this form of HCM (8). This low diagnostic sensitivity can be a contributing factor to the high mortality rate of TnT related HCM, making understanding its etiology very important. Mutations in TnT mostly seem to be associated with changes in calcium sensitivity (10). Three mutations seem to be prevalent, each having varying affects on calcium sensitivity. The TnT-Arg278Cys (R278C) mutation, not without some debate (15), has been found to have negligible effects on calcium handling, resulting in a relatively better prognosis for the patient (11). TnT-Phe110Ile (F110I) and Ile79Asn (I79N) mutations both show a respective increase in calcium sensitivity (10). Their pathologies differ from most HCM in that very little fibrosis or hypertrophy is seen (12). This is unique, as most HCM has associated fibrosis, which results in re-entrant tachycardias and possible fibrillation (13). But with I79N and associated mutations, re-entrant tachycardias have been observed in the absence of any fibrosis (14). Both the etiology of these mutations and resulting pathology has been researched extensively in murine and porcine models (14, 15). The I79N, R278C, and F110I mutations were first identified and characterized by Watkins et al. (16). Families exhibiting HCM had their DNA sequenced and, using statistical analyses, polymorphisms were
    Open Document