A novel TSC2 missense variant associated with a variable phenotype of tuberous sclerosis complex: case report of a Chinese family

Abstract

BackgroundTuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the development of hamartomas in multiple organs, including the brain, heart, skin, kidney, lung and retina. A diagnosis of TSC is established with a recently revised clinical/radiological set of criteria and/or a causative mutation in TSC1 or TSC2 gene.Case presentationWe report a Chinese TSC family with two siblings presenting with multiple hypomelanotic macules, cardiac rhabdomyomas and cortical tubers associated with a small subependymal nodule. The older child had seizures. A novel heterozygous missense variant in the TSC2 gene (c.899G > T, p.G300 V) was identified and shown to be inherited from their father as well as paternal grandfather, both of whom presented with variable TSC-associated signs and symptoms.ConclusionWe identified a novel heterozygous TSC2 variant c.899G > T as the causative mutation in a Chinese family with TSC, resulting in wide intrafamilial phenotypic variability. Our study illustrates the importance of clinical evaluation and genetic testing for family members of the patient affected with TSC.

Unmasking Antenatal Tuberous Sclerosis and 13 Years Retrospective Review of Its Diverse Presentations, Clinical-Imaging Follow Up and Learning the Latest Advances in Management

“…The alarming truth lies in the emerging data. The coexistence of cardiac rhabdomyoma and Tuberous Sclerosis (an autosomal dominant, neurocutaneous multi-organ disorder) is 80-90% [5][6][7][8][9][10]. Frudit et al [1] have already reviewed the existing sparse database of 31 cases of coexistence of rhadbdomyoma and TSC till 2019 and published autopsy findings of the most dreaded version of cardiac rhabdomyoma, similar to patient number 4 in our series.…”

Multiple cardiac rhabdomyomas in tuberous sclerosis complex: case report and review of the literature

“…Whereas the newborn presented cardiovascular features, the aunt and grandfather had a history of dermatological lesions, the mother exhibited mostly neurological and dermatological symptoms and had pulmonary, hepatic, and renal image findings. Wide intrafamilial phenotypic variability has been reported,43 , 44 and family members may sometimes be affected, yet escape the previous diagnosis because of a milder phenotypic presentation 45. At times, the disease can only be diagnosed through genetic testing or image findings, leaving the patient otherwise healthy until adulthood, while in other cases it can present clinical symptoms with a broad spectrum of severity.…”

Prenatal Phenotypical Discrepancy in Monozygotic Twins with Tuberous Sclerosis Complex

“…TSC cases show high clinical variabilities among family members and even in monozygotic twins. 8 Some postnatal cases have suggested clinical discordance in monozygotic twins suffering from TSC. Martin et al .…”

“…TSC cases show high clinical variabilities among family members and even in monozygotic twins. 8 Some postnatal cases have suggested clinical discordance in monozygotic twins suffering from TSC. Martin et al 9 described one pair of monozygotic twins who had similar levels of motor delay and mental retardation.…”