Abstract
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome with an autosomal dominant
pattern of inheritance. It is a multisystem genetic disease caused by mutations in
the TSC1 and TSC2 genes. The neuroradiographic findings of TSC include cortical dysplasia (cortical
tubers and cerebral white matter radial migration lines), subependymal nodules, and
subependymal giant cell astrocytoma. In this article, we describe an interesting case
of TSC with an extremely rare radiographic finding of focal right megalencephaly.
Molecular genetic testing detected a heterozygous c.3814+2T>G (p.?) variant, not previously
described in the literature. As per the 2012 International Tuberous Sclerosis Complex
Consensus Group guidelines and the findings of the genetic testing, this mutation
most probably should be considered as a pathogenic variant. There are few cases of
hemimegalencephaly (HME) reported in the literature, associated with TSC. To our knowledge
focal megalencephaly is an extremely rare neuroradiographic finding in patients with
TSC and has been previously reported only once by Griffiths et al based on clinical
diagnostic criteria. Despite the uncommon association, TSC is the only neurocutaneous
syndrome with similar histological appearance to HME. It is recognized that the pathological
features in TSC and HME are due to abnormal cell proliferation, migration, and organization
which could also be a possible mechanism for the development of focal megalencephaly.
The uncommon association of HME and TSC with cytological similarities makes us wonder
if there could be similarities in the pathogenesis of these two conditions. The advances
in molecular genetic testing, increasing use of next-generation sequencing, and discovery
of new pathogenic variants could answer some of these questions.
Keywords
tuberous sclerosis - focal megalencephaly - updated diagnostic criteria for TSC 2012
- TSC2 variant - epilepsy surgery
