Fetal and neonatal cardiac tumor diagnosed as Tuberous Sclerosis associated rhabdomyomas resulting from novel pathogenic missense variant detected in TSC2 gene: A case report

Fetal cardiac tumors are often the first clinical manifestation of tuberous sclerosis (TS) when fetal ultrasound screening is performed. TS is an autosomal dominant disorder caused by the mutations in TSC1 or TSC2 genes. Here we report a case of a patient with a fetal and neonatal cardiac tumor who underwent a genetic analysis for TS after birth. Multiple fetal cardiac tumors were detected on ultrasonography at 24 weeks, gestation with no other manifestation. Neither epilepsy nor mental retardation was seen after birth. Once the parents were provided careful genetic counseling, a genetic analysis for TS was performed when the patient was 2 years old that demonstrated a novel pathogenic missense variant: c.1072T>C, p.Trp358Arg in the TSC2 gene with 30% mosaicism. This pathogenic variant is located on exon 10 of the TSC2 gene, which encodes the hamartin binding domain, leading to impair inhibitory function of the hamartin-tuberin complex, which activates mammalian target of rapamycin(mTOR) activity. The cardiac tumors were diagnosed as rhabdomyomas, a major clinical feature of TS, since the penetrance of this gene variants are thought to be 100%. We speculate that this new missense variant in TSC2 gene with 30% mosaicism will be associated to the milder phenotype of TS since the regression of the rhabdomyomas is the only manifestation in this patient. We hope that this case report might help clinicians and genetic counselors manage individualized surveillance plans for patients with TS.