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Extreme Clinical Variability of Dilated Cardiomyopathy in Two Siblings With Alström Syndrome

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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.

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Acknowledgments

We thank the patients and their families for their participation in this study. J. D. M., G. B. C, and J. K. N. were supported by a grant from the National Institutes of Health Grant No. HD036878. We are grateful to Alström Syndrome International and Alström Syndrome Canada for support for the Asper Ophthalmics microarray evaluation. The Jackson Laboratory institutional allele typing and sequencing shared services were supported by the United States Public Health Service, National Institutes of Health (Grant No. CA034196).

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Authors and Affiliations

  1. Kupat Holim Meuhedet, Um El Fahem, Israel

    Jamal Mahamid

  2. Pediatric Cardiology Unit, Mayer Medical Center, Haifa, Israel

    Avraham Lorber

  3. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Avraham Lorber, Yoseph Horovitz, Stavit A. Shalev & Ronen Spiegel

  4. Pediatric Department A and Genetic Institute, Emek Medical Center, 18101, Afula, Israel

    Yoseph Horovitz, Stavit A. Shalev & Ronen Spiegel

  5. The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA

    Gayle B. Collin, Jürgen K. Naggert & Jan D. Marshall

Authors
  1. Jamal Mahamid
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  2. Avraham Lorber
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  3. Yoseph Horovitz
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  4. Stavit A. Shalev
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  5. Gayle B. Collin
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  6. Jürgen K. Naggert
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  7. Jan D. Marshall
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  8. Ronen Spiegel
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Corresponding author

Correspondence to Ronen Spiegel.

Additional information

Jamal Mahamid and Avraham Lorber contributed equally to this study.

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Mahamid, J., Lorber, A., Horovitz, Y. et al. Extreme Clinical Variability of Dilated Cardiomyopathy in Two Siblings With Alström Syndrome. Pediatr Cardiol 34, 455–458 (2013). https://doi.org/10.1007/s00246-012-0296-6

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  • DOI: https://doi.org/10.1007/s00246-012-0296-6

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