Abstracts

Rationale: Introduction:Tuberous sclerosis complex is a genetic disorder with autosomal dominant pattern of inheritance and is initially recognized as childhood disease. We described a 45 year old woman, who had no family history or any clinical manifestations of tuberous sclerosis, presented with new onset seizure as the first clinical symptom of neurocutaneous disorder which normally presents in children. Diagnosis of tuberous sclerosis complex can be difficult in adult population because of variable expressivity and incomplete penetrance. Methods: Case:A forty-five year-old woman with no significant family history presented after first-time new onset complex partial seizure. She had an episode of partial complex seizure with secondary generalization which lasted for about minutes. After a few minutes, she regained her consciousness but she was in post-ictal with flaccid weakness in her left side of her body. All cranial nerves were intact with two small nodules on the left iris and a nodule on the nose. There are several ash leaf spots "hypopigmented macules". CT scan head was done showed scattered areas of dystrophic coarse parenchymal calcification in the subependymal region and in both cerebellar hemispheres. Antiepileptic drug was given through intravenously. MRI showed innumerable bilateral subcortical and cortical T2/Flair hyper intensities (cortical tubers) many of which demonstrate intrinsic T1 hyperintensity both pre and post contrast with multiple calcified subependymal nodules which consistent with TSC according to the diagnostic criteria of Roach et al., 1998. Whole CT Chest, abdomen, pelvis, and TTE were done which showed no lesion in the liver, lung, kidney and heart. TSC1 and TSC2 genetic test was performed which showed a DNA sequence variant of unknown clinical significance in TSC2 gene (TSC2 c.1443 G>A) which indicate of pathogenic variant. Her seizure was well controlled with levetiracetam. Results: DISCUSSION: Tuberous sclerosis complex is neurocutaneous autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 to 10,000 live births. Only 7 to 37 percent of newly diagnosed cases have a family history of TSC. Two thirds of TSC cases result from sporadic genetic mutations in TSC1 or TSC2, not inheritance. In our case, TSC may result from somatic mosaicism where the mutation occurred during the patient's development and after fertilization. Once a ‘de novo' germline mutation occurs in an individual, their offspring may inherit TSC, which then appears familial in subsequent generations. Conclusions: Neurological presentation of tuberous sclerosis occurs typically in children with seizures and intellectual impairment. However approximately 50% of patients who fulfill the diagnostic criteria have normal intellect and 15% remain free from seizures. The exceptionally mild disease in our patient may be due to to ​somatic mosaicism where a postzygotic new dominant mutation only affects a proportion of cells and to a varying extent in different tissues.