title: Extreme clinical variability of dilated cardiomyopathy in two siblings with Alström syndrome.
abstract: Alström syndrome (ALMS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene. We report two brothers, 3 and 4 years of age and diagnosed with ALMS, who initially presented in infancy with severe dilated cardiomyopathy during febrile respiratory infection. The disease course in the two siblings was marked by significant intrafamilial variability. Although cardiomyopathy in the older sibling has mainly resolved thus allowing for the discontinuation of medical therapy, heart function in the younger sibling continues to deteriorate despite maximal drug support with furosemide, carvedilol, captopril, and aldospirone. Genetic analysis revealed homozygous mutations, c.8008C>T (R2670X), in ALMS1 resulting in premature protein truncation. This report further emphasizes the exceptional intrafamilial variability of ALMS, mainly during the natural course of cardiac disease.
authors.affiliation: Kupat Holim Meuhedet, Um El Fahem, Israel.
authors.forename: Jamal
authors.initials: J
authors.lastname: Mahamid
authors.forename: Avraham
authors.initials: A
authors.lastname: Lorber
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Horovitz
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.forename: Ronen
authors.initials: R
authors.lastname: Spiegel
mesh_terms: D056769:Alstrom Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D006720:Homozygote; D006801:Humans; D008297:Male; D011506:Proteins / Q000235:genetics*; D035781:Siblings
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D011506:Proteins; D004247:DNA