## 4 Discussion
Interesting evidence was also reported for PMMR, offering heart morpho-volumetric information (i.e., detailed data on cardiac wall thickening and weight), which can have a relevant applicative implication for the differential diagnosis between primary and secondary myocardial hypertrophy [34; 35; 36]. PMMR can provide other data suggesting HCM, such as the myocardial bridge, ventricular crypts, and anomalies of the papillary muscles and sub-mitral apparatus [35]. However, this investigation cannot be considered a substitute for autopsy findings being associated with a false positive; in fact, [PERSON] et al. [37] described, in one case, radiological evidence of mid-posterior wall hypertrophy, at the level of papillary muscle, that was not confirmed at autopsy. The effect of myocardial rigor mortis on wall thickness was also analyzed to improve the PMMR performance in HCM diagnosis. In the clinical setting, the HCM diagnosis is performed using the end-diastolic wall thickness of the left ventricle, which, in the post-mortem setting, is not feasible because of rigor mortis. In fact, the reserves of ATP in cardiac muscle, as well as in skeletal muscle, are consumed, and the heart may remain paralyzed (rigor mortis) in both early and mid-diastolic phases without any relation to the time interval between death and PMMR or to sex, age, cardiac weight, and body habitus [87]. Thus, a study suggested applying a standard deviation of wall thickness cut-off >2.4 as a diagnostic parameter in a forensic context [36]. The genetic test is a fundamental diagnostic investigation for the assessment of HCM. This cardiomyopathy has an inherited genetic trait, which is primarily autosomal dominant, in about half of cases [88]. Cohort studies reported that in about 40-60% of the cases, there is a single variant responsible for the disease [89]. There are also sporadic cases that can have a monogenic cause, which is possibly related to either an incomplete penetrance of a variant inherited from a parent or is due to de novo variants or, less commonly, to autosomal recessive inheritance [88]. In about the 10% of the cases, HCM is due to other genetic/non-genetic diseases, among which are malformation syndrome (i.e., Noonan and LEOPARD syndrome), metabolic disorders (i.e., Anderson-Fabry and Pompe disease), mitochondrial diseases, neuromuscular diseases, and infiltrative diseases (i.e., amyloidosis) [90]. In these cases, it is possible to detect other morphological alterations in the cardiac muscle and/or other organs and systems. Therefore, a multidisciplinary evaluation is necessary among pathologists, geneticists, and relevant specialists and remains crucial to reach an accurate post-mortem differentiation [91]. HCM is a relatively common finding in [PERSON] syndrome and is usually associated with both other cardiac anomalies, such as pulmonary valve dysplasia causing stenosis of the right ventricular outflow tract, atrial septal defect, and/or aortic bicuspid valve, and systemic anomalies, such as delayed growth, cryptorchidism, and/or blood clotting abnormalities. The genetic bases underlying the development of the pathology are also different: in HCM-Noonan-related forms, the most commonly detected mutation appears to be that of the RAF1 and PTPN11 genes [91; 92]. Fabry disease is a recessive lysosomal storage disease, linked to the X chromosome, due to the deficiency of the enzyme \(\alpha\)-galactosidase A (\(\alpha\)-Gal A), which is secondary to the GLA gene mutation. This deficiency causes a progressive accumulation of globotriasylceramide (GL-3) and related glycophinfolipids in cardiac, renal, neural, vascular, ocular and skin tissues. Cardiac involvement is characterized by a broad spectrum of signs and symptoms, including hypertrophic cardiomyopathy, which is associated with arrhythmias, coronary artery disease (primarily small vessel disease), and heart failure [93].