An unusual case of familial hypertrophic cardiomyopathy with left ventricular systolic dysfunction: a still unsolved diagnosis

A 35-year-old woman was referred to our centre for clinical management of hypertrophic cardiomyopathy (HCM) with left ventricular (LV) systolic dysfunction (end-stage evolution). She was recently diagnosed elsewhere because of palpitations. Her 7-year-old daughter underwent familiar screening and she was diagnosed with classic HCM. She was completely asymptomatic without extracardiac or systemic manifestations. During the following years, they both experienced a similar clinical course with worsening dyspnoea and progressive deterioration of LV systolic function. They both underwent heart transplantation, the mother at the age of 47 and the daughter at the age of 23, respectively. Many diagnostic hypotheses, including sarcomeric HCM, Anderson-Fabry disease, glycogen storage diseases and mitochondrial cardiomyopathies have been taken into account. The diagnostic work-up included serial electrocardiogram and echocardiographic assessments, pathologic evaluation of the explanted hearts and genetic analysis of 8 sarcomeric and 3 metabolic genes. Even if a shared HCM phenotype (LV systolic dysfunction in two first-degree female family members associated with a likely autosomal dominant inheritance and absence of extracardiac or multisystemic manifestations) could support a temptative diagnosis of sarcomeric HCM , a definitive diagnosis could not be reached, due to the lack of genetic analysis to confirm such diagnosis.