Marfan syndrome (MFS) and Loeys-Dietz syndrome type 4 (LDS4) are two hereditary connective tissue disorders. MFS displays ectopia lentis as a distinguishing, characterising feature, and thoracic aortic ectasia, aneurysm, dissection, and systemic features as manifestations overlapping with LDS4. LDS4 is characterised by the presence of hypertelorism, cleft palate and/or bifid uvula, with possible ectasia or aneurysms in other arteries. The variable age of onset of clinical manifestations makes clinical diagnosis more difficult. In this study, we report the case of a patient with Marfan syndrome diagnosed at our centre at the age of 33 on the basis of typical clinical manifestations of this syndrome. At the age of 38, the appearance of ectasia of the left common iliac artery and tortuosity of the iliac arteries suggested the presence of LDS4. Next Generation Sequencing (NGS) analysis, followed by Array-CGH, allowed the detection of a novel chromosomal deletion including the entire TGFB2 gene, confirming not only the clinical suspicion of LDS4, but also the clinical phenotype associated with the haploinsufficiency mechanism, which is, in turn, associated with the deletion of the entire gene. The same mutation was detected in the two young sons. This emblematic case confirms that we must be very careful in the differential diagnosis of these two pathologies, especially before the age of 40, and that, in young subjects suspected to be affected by MFS in particular, we must verify the diagnosis, extending genetic analysis, when necessary, to the search for chromosomal alterations. Recently, ectopia lentis has been reported in a patient with LDS4, confirming the tight overlap between the two syndromes. An accurate revision of the clinical parameters both characterising and overlapping the two pathologies is highly desirable.

Sudden cardiac death is defined as sudden death due to a confirmed cardiovascular disease or when there is no explanation after medico-legal autopsy and arrhythmogenic, possibly hereditary etiology is presumed. Molecular autopsy should be indicated in all cases of sudden cardiac death due to suspected cardiomyopathy and hereditary arrhythmic syndrome. It should also be considered in thoracic aortic dissection. These hereditary cardiovascular diseases account for the majority of sudden cardiac death cases in the young up to 40 years of age. They are mostly inherited in an autosomal dominant manner carrying a 50% risk of passing the diasease-causing mutation to the offspring. In fact, all first-degree relatives have a high risk of developing the disease associated with sudden cardiac death. Hence, knowledge of the exact cause of death derived from molecular autopsy combined with a cardiologic and targeted genetic examination of first-degree relatives may help us detect other at risk family members and provides us with an opportunity to prevent further sudden deaths in the family by means of timely preventive measures. Forensic pathologists play a key role in this process of primary prevention of sudden death. They should retain tissue samples for DNA analysis whenever a hereditary cardiovascular disease is suspected. They should also recommend to the relatives a thorough cardiogenetic examination at one of the specialized centres. A multipdisciplinary team including cardiologists, geneticists, psychologists, forensic pathologists and coroners should be involved in the investigation of sudden cardiac death in the young.