X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome

A number of families with X linked dilated cardiomyopathy with onset in infancy or childhood have now been described, with varying clinical and biochemical features. Of these, one condition, Earth syndrome (ETHS), can be diagnosed clinically by the characteristic associated features of skeletal myopathy, short stature, and neutropenia, but not all of these features are always present. Molecular genetic studies have delineated the gene for ETHS, which maps to distal Xq28, from the gene for so called X linked dilated cardiomyopathy (XLCIM), a teenage onset dilated cardiomyopathy, recently mapped to the 5' portion of the dystrophin locus at Xp21. We report a large family in which male infants have died with congenital dilated cardiomyopathy, and there is a strong family history of unexplained death in infant males over at least four generations. Death always occurred in early infancy, without development of the characteristic features associated with Earth syndrome. Molecular analysis localised the gene in this family to Xq28 with lod scores of 2.3 at θ = 0.0 with dinucleotide repeat markers, p26 and p39, near DXS15 and at F8C. The proximal limit to the localisation of the gene in this family is defined by a recombinant at DXS296, while the distal limit could not be differentiated from the telomere. This localisation is consistent with a hypothesis of allelic and clinical heterogeneity at the BTHS locus in Xq28.