Different pathologies can be the cause of a sudden unexpected death, such as congenital malformations, cardiomyopathies and vascular hyaline [12–14]. Undiagnosed congenital heart diseases are in particular very frequent in paediatric autopsies [15, 16]. In the case of sudden neonatal death here presented a congenital cardiomyopathy was associated with brainstem developmental alterations and polymorphism of the serotonin transporter gene.
These findings primarily confirm the link we have previously highlighted in a large group of perinatal sudden deaths (28 SIDS and 12 SIUDS victims) between neuropathological raphe defects and serotonin transporter promoter region polymorphisms . In particular, we have suggested the presence of the L allele as a predisposing factor for morphological developmental defects of the brainstem raphe nuclei leading to sudden death.
It is well known that the neurons of the raphe nuclei, producing the neurotransmitter serotonin, besides playing a trophic role during neuronal development in the fetal brain , are involved in the breathing mechanism after birth, modulating the ventilatory responses to hematic oscillations of pO2, pCO2 and pH in order to maintain these within physiological levels . We may speculate that the severe hypoplasia of all the raphe nuclei that we observed in this case, plausibly a consequence of the genotypic presence of the 5-HTT L allele, may have prevented eupneic breathing, so leading to death.
Furthermore, in our previous study  we indicated that hypoplasia of the raphe nuclei and the L/L or S/L genotypes are significantly associated to maternal smoking in pregnancy. In support of this concept, experimental studies in rats have shown that prenatal nicotine absorption can directly act on the expression of serotonin transporter genes . In this case, however, the mother admitted no history of cigarette smoking. Nevertheless, it should be considered that a retrospective assessment of the maternal smoking habit, mainly if performed after the fatal event, is sometimes unreliable . Smoker mothers are generally reluctant to honestly report tobacco use, because of feelings of guilt.
The neuropathological and genetic features observed in this case were exacerbated by the additional presence of accessory fibers in the cardiac conduction system and of hypertrophy of the heart myocytes. The Mahaim fiber is an accessory atrio-ventricular communication quite frequent in perinatal unexplained death, that, under particular conditions and/or neurovegetative stimuli, is liable to provoke electrical dyshomogeneity, instability and desynchronization, raising the risk of malignant functional arrhythmias.
Hypertrophic cardiomyopathy (HCM) is the most prevalent cause of sudden cardiac death in younger people, frequently determined by mutations in genes coding for proteins of the sarcomere . Neonatal clear HCM is, instead, a very rare observation, being a progressive heart disease that, though present from birth, develops over time. In a retrospective study performed on DNA extracted from paraffin blocks tissues of a wide group of SIDS victims, Brion et al.  observed four different polymorphic genes associated to HCM (namely, MYBPC3; TNNT2; MYH6; TNN13) in 10% of cases, without pathological manifestations. Thus, the diagnosis of a clearly evident HCM in the infant here presented reinforces the importance of this report. Research aimed at evaluating the expression of specific HCM genes is now in progress in our laboratory in order to verify whether multiple genetic variants may be at the basis of this complex series of congenital anatomopathologic findings.
In conclusion, we cannot define this report as a true SIDS case, since SIDS is defined as a sudden infant death that remains undetermined after all investigative avenues have been exhausted, but given the combination of multiple pathological events underlying the sudden death, as a border-line SIDS case it does, however, contribute to provide further insights into this tragic phenomenon.