Tuberous sclerosis complex without tubers and subependymal nodules: a phenotype–genotype study

Authors

  • S. Boronat,

    1. Department of Neurology, Herscot Center for TSC, Massachusetts General Hospital, Boston, MA, USA
    2. Department of Pediatric Neurology, Vall d' Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
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  • E.A. Shaaya,

    1. Department of Neurology, Herscot Center for TSC, Massachusetts General Hospital, Boston, MA, USA
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  • C.M. Doherty,

    1. Department of Neurology, Herscot Center for TSC, Massachusetts General Hospital, Boston, MA, USA
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  • P. Caruso,

    1. Department of Neuroradiology, Massachusetts General Hospital, Boston, MA, USA
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  • E.A. Thiele

    Corresponding author
    1. Department of Neurology, Herscot Center for TSC, Massachusetts General Hospital, Boston, MA, USA
    • Corresponding author: Elizabeth A. Thiele, MD, PhD, Pediatric Epilepsy Program, Massachusetts General Hospital, 175 Cambridge Street, Suite 340, Boston, MA 02114, USA.

      Tel.: 617 726 0241;

      fax: 617 726 0230;

      e-mail: ethiele@partners.org

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  • The authors declare no conflict of interest.

Abstract

Tuberous sclerosis complex (TSC) is caused by a mutation in the TSC1 or TSC2 genes. However, 15% of patients have no mutation identified. Tubers and subependymal nodules (SENs) are the typical brain lesions in TSC and are present in 90–95% of patients. The objective of this study is to characterize the specific genotype–phenotype of patients without these lesions. We analyzed the features of 11 patients without typical TSC neuroanatomic features. Ten had TSC1/TSC2 mutational analysis, which was negative. Clinically they had lesions thought to be of neural crest (NC) origin, such as hypomelanotic macules, facial angiofibromas, cardiac rhabdomyomas, angiomyolipomas, and lymphangioleiomyomatosis. We hypothesize that patients without tubers and SENs reflect mosaicism caused by a mutation in TSC1 or TSC2 in a NC cell during embryonic development. This may explain the negative results in TSC1 and TSC2 testing in DNA from peripheral leukocytes.

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