Histiocytoid cardiomyopathy (ORPHA:137675)
A rare arrhythmogenic disorder characterized by cardiomegaly, severe cardiac arrhythmias or sudden death, and the presence of histiocyte-like cells within the myocardium.
Epidemiology
Approximately 100 patients have been described in the literature to date. There is a female predominance with a female:male ratio between 3:1 to 4:1.
Clinical description
The majority of reported cases involve children under 2 years of age, indeed histiocytoid cardiomyopathy is a disease of infancy and early childhood. Clinically, the disease may manifest as various types of incessant arrhythmia (including atrial and ventricular fibrillation, supraventricular and ventricular tachycardia and Wolff-Parkinson-White syndrome) but sudden death due to cardiac arrest is a common presentation (20%). Lethal arrhythmias might be triggered by fever. Association with other cardiac defects (ventricular and atrial septal defects, hypoplastic left heart syndrome, endocardial fibroelastosis and left ventricle noncompaction) and with extracardiac anomalies (hypotonia, MIDAS syndrome, Peters anomaly, and congenital glaucoma) has also been reported in 16 and 17% of cases respectively.
Etiology
Etiology of histiocytic cardiomyopathy remains unknown. It was largely suspected to be caused by a developmental anomaly of the conduction system; however, genetic testing support various molecular basis. Mutation in cytochrome b, as well as A8344G mitochondrial DNA mutation have been described but seem to be sporadic variants. Whole Genome Expression Analysis support cluster of candidate gene at 1q21.3c, 2q12.1a and a decrease in copy number of the genes encoding S100A calcium binding protein, along with a strong decrease in interleukin 33 expression.
Diagnostic methods
Histiocytoid cardiomyopathy is suspected on the basis of clinical presentation, electrocardiogram, echocardiography, cardiac magnetic resonance imaging, myocardial biopsy or at autopsy. Unfortunately diagnosis is, typically post-mortem by histological evaluation, findings are pathognomonic for the disease and include yellow-tan nodules in the myocardium and, in some cases, in the subendocardial and subepicardial areas. The nodules are composed of nests of foamy histiocyte-like cells with a granular cytoplasm containing lipid droplets and abundant atypical mitochondria. These abnormal myocytes are found mainly in the ventricles but involvement of the valves has also been reported.
Differential diagnosis
As sudden infant death is frequently the presenting manifestation, sudden infant death syndrome (SIDS) is often the initial diagnosis in these cases but can be ruled out by histological evaluation of the myocardial tissue.
Genetic counseling
There is a familial tendency of 5%; however, mode of inheritance (X-linked dominant inheritance and autosomal recessive) is still debated. Female predominance is not understood.
Management and treatment
Management options for patients presenting with arrhythmias include surgical removal of the nodular lesions, electrophysiological mapping and radiofrequency ablation of the arrhythmias. Heart transplantation have been proposed for few patients. Antiarrhythmics are generally ineffective but one patient showed a good response to treatment with amiodarone.
Prognosis
The prognosis in general is poor and the disease is usually fatal.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Dr Alice MALTRET