Prenatal Phenotypical Discrepancy in Monozygotic Twins with Tuberous Sclerosis Complex

Abstract

Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder characterized by the development of hamartomas in the brain, heart, skin, kidney, lung, retina, and so on. One fetus from family 1 had a cardiac rhabdomyoma from 21 weeks and 6 days of gestational age, and developed multiple rhabdomyomas and tubers in the brain at 23 weeks and 5 days. The counter monozygotic twin fetus remained negative throughout the pregnancy according to imaging examination. A nonsense mutation in TSC2 (c.4762C>T, p.Gln1588∗) was identified in both twins, but not in the mother. Family 2 was one pair of twin fetuses caused by a microdeletion of exon 30 within TSC2 inherited from their apparently asymptomatic mother with mosaic status. The larger fetus was identified as having the first cardiac rhabdomyoma from 17 weeks and 4 days of gestational age. The smaller fetus developed multiple rhabdomyomas until 25 weeks and 6 days of gestational age. Both families terminated the pregnancy. Here, we provide intrauterine examples of clinical variability among monozygotic twins suffering from TSC.