Absence of subependymal nodules in patients with tubers suggests possible neuroectodermal mosaicism in tuberous sclerosis complex

Authors

  • Susana Boronat,

    1. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    2. Department of Paediatric Neurology, Vall d'Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
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  • Paul Caruso,

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

    Corresponding author
    1. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    • Correspondence to Elizabeth A Thiele at Pediatric Epilepsy Program, Massachusetts General Hospital, 175 Cambridge Street, Suite 340, Boston, MA 02114, USA.

      E-mail: ethiele@partners.org

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Abstract

Aim

Patients with tuberous sclerosis complex (TSC) with brain involvement usually have both tubers and subependymal nodules (SENs) and the occurrence of one lesion without the other seems to be rare. The aim of this study was to assess the specific clinical manifestations and genotype of patients with one type of lesion or the other but not both.

Method

The magnetic resonance images of 220 patients with TSC were reviewed, and patients with either tubers or SENs, but not both, were identified.

Results

Out of a total of 220 patients (95 males, 125 females; mean age 22y 9mo, range 9mo–81y), six (3%) had tubers without SENs (two males; four females; mean age 34y 10mo, range 11–48y); however, no patients with SENs and without tubers were identified. No mutation was identified (NMI) in any of the six patients who underwent mutational analysis of TSC1 and TSC2. Five of the six patients had three or fewer tubers.

Interpretation

We found no patients with SENs but without tubers among our cohort. In all patients with tubers but without SENs, mutational studies of TSC1/TSC2 were negative, and the majority of these had three or fewer tubers. A possible mechanism for patients with NMI and an absence of SENs is a mosaicism with a first postzygotic mutation in the neuroectoderm.

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