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Maternal inheritance in cyclic vomiting syndrome with neuromuscular disease

Authors

  • Richard G. Boles,

    Corresponding author
    1. Division of Medical Genetics, Childrens Hospital Los Angeles, Los Angeles, California
    2. Department of Pediatrics, University of Southern California School of Medicine, Los Angeles, California
    • Medical Genetics Box 90, Childrens Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027.
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  • Kathleen Adams,

    1. Cyclic Vomiting Syndrome Association, USA/Canada
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    • The author Kathleen Adams is the President.

  • Masamichi Ito,

    1. Division of Medical Genetics, Childrens Hospital Los Angeles, Los Angeles, California
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  • B.U.K. Li

    1. Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Chicago, Illinois
    2. Department of Pediatrics, Northwestern University, Chicago, Illinois
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Abstract

Cyclic vomiting syndrome (CVS), characterized by severe discrete episodes of nausea, vomiting, and lethargy, is a predominately childhood condition associated with migraine and dysautonomic features. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested by a strong maternal bias in the inheritance of migraine, and the recent findings of mtDNA variants in a few children with CVS and additional neuromuscular disease manifestations (“CVS+”). A clinical interview using a questionnaire was administered (generally) to one parent of 62 children with CVS+. Non-senile disease manifestations, including migraine, myopathy, seizures, and dysautonomia-like symptoms, were far more common in matrilineal versus non-matrilineal relatives, including being present in 75% of the mothers versus in only 11% of the fathers (P < 0.001). Overall, maternal inheritance is suggested in 86% of the families (in 65% strongly so). Disease manifestations in subjects and their affected matrilineal relatives are predominately intermittent and consistent with dysautonomia, including increased vital sign fluctuations. Body fluid metabolites and muscle biopsy findings are consistent with mitochondrial dysfunction in most cases tested. We conclude that mtDNA sequence variants are at least risk factors in the development of disease in most children at this “severe” end of the CVS spectrum, likely involving a maternally inherited propensity towards dysautonomia. © 2003 Wiley-Liss, Inc.

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