Neurological manifestations in Tuberous Sclerosis Complex

Abstract

Tuberous Sclerosis Complex (TSC) is a rare multisystemic neurocutanous autosomal dominant syndrome. The cause of this disorder is a germinal mutation in TSC1 or TSC2 genes. Here, we report a case of a patient presenting tuberous sclerosis complex with TSC2 gene mutation. Our patient is aged 2 years and 6 months old, youngest of two siblings from a non-related marriage. The symptoms are neonatal hypotonia, epilepsy, psychomotor retardation, intellectual deficiency, dolichocephaly, above-average height, facial dysmorphia, and diffuse achromic spots on the chest and abdomen. The family survey found multiple siblings with various symptoms such as bony deformities, epilepsy, language delay, partial deafness, congenital renal malformation, and intellectual disability. The patient's brain MRI showed areas of cortico-subcortical hypodensity and subependymal nodules. The exome sequencing has detected a probably pathogenic heterozygous nonsense variant in the TSC2 gene: NM_000548.3: c.965C>A p.(ser322*). The variant identification was not performed in the parents due to lack of resources. TSC1 and TSC2 genes encode for hamartin-tuberin complex. Mutations in these genes cause hyperactivation of the mTOR pathway leading to the tumor development in several organs including the brain. The neurological manifestations of TSC can be epilepsy, intellectual deficiency, autism and behavioral disorders. The epilepsy is considered the main neurological symptom found in 70-90% of cases. Moreover, mutations in the TSC2 gene lead to severe epilepsy compared to TSC1 mutation. The TSC is a disorder with an important neurological component. Investigations of epilepsy, brain MRI and genetic analysis may play an essential role in TSC diagnosis.
 Keywords: Tuberous Sclerosis Complex, Neurology, Genetic mutation, TSC2.