Cardiomyopathy, Infantile Histiocytoid

A number sign (#) is used with this entry because this disorder is caused by mutation in the gene encoding mitochondrial cytochrome b (MTCYB; 516020).

Description

Histiocytoid cardiomyopathy, which was initially described by Voth (1962), goes by various names, including infantile xanthomatous cardiomyopathy (MacMahon, 1971), focal lipid cardiomyopathy (Bove and Schwartz, 1973), oncocytic cardiomyopathy (Silver et al., 1980), infantile cardiomyopathy with histiocytoid change (Ferrans et al., 1976), and foamy myocardial transformation of infancy (Yatani et al., 1988). The disorder is a rare but distinctive entity of infancy and childhood characterized by the presence of characteristic pale granular foamy histiocyte-like cells within the myocardium. It usually affects children younger than 2 years of age, with a clear predominance of females over males. Infants present with dysrhythmia or cardiac arrest, and the clinical course is usually fulminant, sometimes simulating sudden infant death syndrome (Andreu et al., 2000).

Clinical Features

Malhotra et al. (1994) presented a table reviewing the 50 reported cases of histiocytoid cardiomyopathy and added 3 'new' cases. They commented on the high frequency of anomalies involving the nervous system and eyes and of oncocytic cells in various glands. Because of the large number of mitochondria present in the histiocytoid cells, they resemble oncocytes. Malhotra et al. (1994) concluded that the syndrome is likely caused by prenatal myocardial or systemic, possibly viral, injury.

Andreu et al. (2000) stated that approximately 61 cases of histiocytoid cardiomyopathy have been reported.

Molecular Genetics

Andreu et al. (2000) restudied a patient with histiocytoid cardiomyopathy reported by Papadimitriou et al. (1984). The patient was an infant girl who died of cardiac arrest at age 4 weeks with typical clinical and pathologic features of histiocytoid cardiomyopathy, but who also had involvement of other organs, including liver (hepatic steatosis) and kidney (acute tubular necrosis). Biochemical studies of cardiac muscle showed isolated complex III deficiency and a marked defect of reducible cytochrome b, the only mtDNA-encoded subunit of complex III of the respiratory chain. Because mutations in the MTCYB gene are often sporadic and can arise during embryogenesis, affecting a limited number of cells and resulting in tissue-specific phenotypes, Andreu et al. (2000) studied the MTCYB gene of this patient and identified a point mutation (516020.0011).