Gene analysis helps identify basis of rare infant heart disorder


Researchers from USA have found differences in gene expression that could indicate a predisposition for histiocytoid cardiomyopathy (HC) in infants a rare arrhythmogenic disorder caractherised by persistent ventricular tachycardia, cardiomegaly, and often sudden death before a child reaches two years of age.

Bahig M Shehata et al (Pediatr Dev Pathol 2011; 14, No. 5: 370–377) compared cardiac tissue from 12 patients with HC and 12 age-matched controls. Researchers found differences in gene expression that could indicate an inherited mutation and predisposition for histiocytoid cardiomyopathy.

According to a preliminary study by Shehata et al (Pediatr Dev Pathol 1998;1:56–69) histiocytoid cardiomyopathy affects females three times more often than males, leading to the theory that it is an X chromosome-linked disorder with prenatal death occurring in males. Eighty percent of the cases occur in whites; 15% in blacks; and 3% in Latin Americans. It is very rare in those of Asian heritage.

This study highlights a worldwide registry of HC started in 1999 (Shehata et al, Thymus and Heart Lyon: IARC Press, 2004; 254–259), attempting to identify the gene responsible for this fatal disorder. The results from the registry showed a family tendency for the disease.

The gene analysis undertaken in the current study found decreased protein expression, or downregulation, in two sets of genes aligned sequentially along the genome. This offers several genes as candidates for the mutation, possibly predisposing individuals to HC.

The downregulation of a particular gene could result in reduced survival of cardiac myocytes, leading to cardiac failure during a baby’s development. The researchers conclude that these candidate genes now will offer a starting point for further research for inherited patterns of mutation. Utilising the HC registry, researchers will seek to confirm the findings of this study and to collect and analyse blood from parents and siblings of HC patients in an effort to further expose the inheritance pattern.