Detection of maternal transmission of a splicing mutation in the TSC2 gene following prenatal diagnosis of fetal cardiac rhabdomyomas mimicking congenital cystic adenomatoid malformation of the lung and cerebral tubers and awareness of a family history of maternal epilepsy

摘要

Objective To present a prenatal diagnosis of familial tuberous sclerosis complex (TSC). Case Report A 29-year-old woman was referred to our institution for amniocentesis at 24 weeks of gestation because of congenital anomaly. The fetus had been found to have an intrathoracic echogenic mass, suspicious of type III congenital cystic adenomatoid malformation of the lung (CCAML). The woman presented with a medical history of epilepsy and had received anticonvulsants but did not disclose the disease entity associated with the epilepsy. Amniocentesis revealed a karyotype of 46,XX. A fetal ultrasound examination at 26 weeks of gestation reported the diagnosis of type III CCAML. At 30 weeks of gestation, magnetic resonance imaging showed multiple cortical tubers in the brain along with an intracardiac mass suspicious of cardiac rhabdomyoma, and a diagnosis of fetal TSC was made. A prenatal ultrasound examination at 30 weeks of gestation revealed multiple cardiac tumors and multiple cortical tubers in the brain. The mother admitted that she had been diagnosed to have TSC. Molecular analysis of the cultured amniocytes and the parental blood showed a splicing mutation of c.2639+1G>C in the splice donor site of intron 22 of TSC2 gene in the mother and the fetus. Conclusion Prenatal diagnosis of an intrathoracic lesion with a family history of parental epilepsy should raise a suspicion of fetal cardiac rhabdomyoma and TSC, and prompt magnetic resonance imaging investigation and molecular genetic analysis if necessary.