Rationale: Rhabdomyoma is the most common type of fetal heart tumors and 50% to 60% of cardiac rhabdomyomas are associated with tuberous sclerosis complex (TSC). TSC is characterized by hamartomas in multiple organ systems including the brain, heart, skin, lungs, and kidneys, resulting in complications such as learning difficulties, epilepsy, behavioral problems, and renal failure. The etiological diagnosis of Rhabdomyoma is very important.
Patient concerns: A 22-year-old G2P0 woman chose to terminate the pregnancy at 24 + 4 weeks of gestation because of the presence of a cardiac space-occupying lesion in the fetus.
Diagnoses: The pathological diagnosis of cardiac neoplasm tissue was cardiac rhabdomyoma, but the etiology was unknown.
Interventions: Targeted exome capture, next-generation sequencing (NGS) and sanger sequencing were performed on peripheral blood lymphocytes and paternal sperm.
Outcomes: Targeted exome capture sequencing revealed a novel heterozygous variant (NM_000548, c.2294delC) in the tuberous sclerosis 2 (TSC2) gene. Sanger sequencing of maternal blood samples showed no mutation at this locus, however, suspected low level mosaicism was observed in paternal blood samples. Deep NGS analysis showed that about 7% paternal alleles from peripheral blood leucocytes and 20% paternal alleles from sperm carried the mutation consistent with somatic and germinal mosaicism.
Lessons: For fetuses suspected of TSC, when pathogenic mutations are detected in the tuberous sclerosis 1 (TSC1) or TSC2 gene, it is recommended that the parents should be screened by deep NGS and their germ cells are screened as well if necessary, which would help to predict the risk of TSC recurrence in the next pregnancy.