The findings of genotype in relation to tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) phenotype: a case report

Introduction: Tuberous sclerosis complex (TSC) is a neurocutaneous disease caused by a mutation in the TSC1 or TSC2 gene. There are several neuropsychiatric manifestations associated with TSC known as TSC-Associated Neuropsychiatric Disorder (TAND). This article concerns neuropsychiatric manifestations in children with the TSC2 gene mutation, with genetic analysis findings using whole-exome sequencing (WES). Case: A 17-year-old girl presented with TSC, absence and focal epilepsy, borderline intellectual functioning, organic psychosis, and renal angiomyolipoma. She was emotionally unstable and preoccupied with irrelevant fears. In the physical examination, we found multiple hypomelanotic maculae, angiofibroma, and a shagreen patch. The intellectual assessment result with the Wechsler Adult Intelligence Scale (WAIS) at 17 was borderline intellectual functioning. Brain magnetic resonance imagery showed cortical and subcortical tubers in the parietal and occipital lobes. WES was conducted, and the result was missense mutation in exon 39 of the TSC2 gene (NM_000548.5:c.5024C>T (NP_000539.2:p.Pro1675Leu)). The Sanger sequencing of the patient’s parents revealed no mutations in the TSC2 gene, confirming the patient’s de novo mutation. The patient was given several anti-epileptic and anti-psychotic drugs. Clinical Discussion: Neuropsychiatric manifestation is a common phenotype in the TSC variant, and psychosis is one of the rare TAND symptoms in children. Conclusion: The neuropsychiatric phenotype and genotype in TSC patients are rarely reported and evaluated. We reported a female child with epilepsy, borderline intellectual functioning and organic psychosis associated with de novo mutation of the TSC2 gene. The organic psychosis is a rare symptom of TAND which also manifested in our patient.