The importance of seeking ALMS1 mutations in infants with dilated cardiomyopathy

As part of a clinical study of Alstrom syndrome (MIM 203800) we sequentially ascertained seven families. Four of the families, pedigrees A–D (table 1), were consanguineous. In total there were 16 living affected individuals, aged 3–25 years. All had cone rod dystrophy that presented in the first 3 months of life with photophobia and nystagmus. The cone rod dystrophy progressed and all were registered blind by the end of the first decade. By the middle of the first decade a characteristic appearance of sunken eyes and a prominent supra-orbital ridge had developed (fig 1A). Truncal obesity became apparent in the first few years of life and all exhibited acanthosis nigricans in their teenage years. None has yet developed symptomatic diabetes. All males of sufficient age failed to enter puberty without hormone support and thereafter developed a female fat distribution (fig 1B). Deafness developed in all cases by the end of the first decade, but varied in severity and symmetry within and between families. All affected individuals were of normal intelligence though they experienced educational difficulties because of their combined and progressive sensory deficits. In all seven families other diagnoses had been made prior to the final diagnosis of Alstrom syndrome, presumably because of the rarity of the condition and the sequential presentation of disease features.1,2 View this table: Table 1  Mutations in ALMS1 causing premature protein truncation in Alstrom syndrome patients exhibiting early onset cardiomyopathy Figure 1  Face and body habitus of a study patient with Alstrom syndrome. (A) The face showing the deep set eyes, a feature that develops in the first few years. (B) The body of a teenage affected male, showing obesity and a female pattern of fat distribution. (Photographs reproduced with permission.) In all seven families the index case had presented with symptoms …