Tuberous sclerosis with negative genetic testing and multiple cerebral cavernomas: A new association (Case report)

Arbune,Anca Adriana; Toron,Basel Robert; Lupescu,Ioan Cristian; Lupescu,Ioana Gabriela; Tatu,Alin Laurentiu; Dulamea,Adriana Octaviana

doi:10.3892/etm.2021.10617

Tuberous sclerosis with negative genetic testing and multiple cerebral cavernomas: A new association (Case report)

Authors:
- Anca Adriana Arbune
- Basel Robert Toron
- Ioan Cristian Lupescu
- Ioana Gabriela Lupescu
- Alin Laurentiu Tatu
- Adriana Octaviana Dulamea
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Affiliations: Neurology Department, ‘Fundeni’ Clinical Institute, 022328 Bucharest, Romania, Department 8‑Radiology, Oncology and Hematology, Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Clinical Medical Department, ReForm UDJ, Faculty of Medicine and Pharmacy, ‘Dunarea de Jos’ University of Galati, 800010 Galati, Romania
Published online on: August 16, 2021 https://doi.org/10.3892/etm.2021.10617
Article Number: 1183
Copyright: © Arbune et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multisystemic involvement usually resulting from mutations in the tuberous sclerosis 1 (TSC1) or TSC2 genes. However, 10 to 25% of patients do not exhibit these mutations. Cerebral cavernous malformations (CCMs) are capillary‑venous malformations that can be asymptomatic or cause variable neurological manifestations, including seizures. Familial CCMs are recognized. In both conditions, specific dermatological lesions are associated. We present the case of a 31‑year‑old female with TSC diagnosed at the age of 18 years who presented with negative genetic testing. She was admitted to our department in 2019 for a sudden increased frequency of focal seizures. Patient examination revealed multiple facial and intraoral angiofibroma, diplopia, right hemihypoesthesia, brisk deep tendon reflexes, and distal leg paresthesia. VideoEEG indicated a frontal paramedian epileptogenic focus. Cerebral magnetic resonance imaging (MRI) and angioMRI identified multiple fronto‑parietal cortical tubers, as well as multiple CCMs, with evidence of bleeding in one. Under antiepileptic drug (AED) and mTOR inhibitor treatment, the seizure frequency significantly improved in a short period of time. This is the first reported case of tuberous sclerosis with negative genetic testing associated with multiple cerebral cavernoma. Such complex patients require multidisciplinary management and detailed genetic testing for increasing knowledge on neuro‑cutaneous disorders.

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