Re: Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous Sclerosis Complex: Case reports and review of literature.

Sir, I read with interest the case report by Al-Futaisi et al. published in the November 2016 issue of SQUMJ which described three children with both autism spectrum disorders (ASDs) and tuberous sclerosis complex (TSC).1 In case one, computed tomography (CT) of the brain appeared normal. In case two, a magnetic resonance imaging (MRI) scan of the brain revealed nodular heterotopias and tubers in the brain, adjacent to the right lateral ventricle; these MRI findings, along with clinical features, confirmed a diagnosis of TSC.1 In the third case, an MRI scan demonstrated multiple cortical and subcortical tubers and subependymal nodules in the brain, which subsequently led to the TSC diagnosis. Although the TSC diagnoses were confirmed by MRI or CT scans in all three cases, the authors stated that it was difficult to correlate MRI findings with the severity of autistic features in each patient.1 However, I believe for the following two reasons that an in-depth evaluation of the MRI findings could help to establish that correlation. First, the appearance of cortical tubers on an MRI represents an important feature in the diagnosis of TSC. Gallagher et al. identified three different types of cortical tubers: (1) type A tubers which were isointense on volumetric T1-weighted images and subtly hyperintense on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images; (2) type B tubers which were hypointense on volumetric T1-weighted images and homogeneously hyperintense on T2-weighted and FLAIR images; and (3) type C tubers which were hypointense on volumetric T1-weighted images, hyperintense on T2-weighted images and heterogeneous on FLAIR images with a hypointense central region surrounded by a hyperintense rim.2 Accordingly, the clinical significance of the dominant tuber type was identified, with patients with type A tubers demonstrating a milder TSC phenotype.2 Moreover, those with tubers predominantly of type C had an increased number of MRI abnormalities—such as subependymal giant cell tumours—and were more likely to have an ASD compared to patients with type A or B tubers.2 Second, cortical tubers vary widely in size, location and appearance.2 Cortical tubers in the temporal lobe and insular area have been found to be associated with ASDs.3 Moreover, the presence of cystic-like tubers on MRI scans might also offer a structural marker for ASDs in TSC.3 On the other hand, large tubers are reportedly more likely to be associated with ASDs, even in comparison to cases with numerous smaller tubers.4