Thanatophoric dysplasia in a dichorionic twin confirmed by genetic analysis at the early second trimester: A case report and literature review
A 30-year-old, nulliparous woman with a twin pregnancy was referred to our hospital during the 15th gestational week for a routine prenatal check. She had suffered from primary infertility secondary to bilateral salpingectomy, and underwent in vitro fertilization. She had conceived triplets and had chosen selective embryo reduction during the 8th gestational week. The couple was healthy, and neither the history of teratogenic exposure nor the family history were remarkable. Initial ultrasonographic examination (Accuvix XQ, Medison Co. Ltd., Seoul, Korea) with a 2-6-MHz transabdominal probe) during the 15th gestational week revealed a thick dividing membrane and two separated placentas, indicating dichorionic placentation. The amount of amniotic fluid of both fetuses was appropriate for gestational age. Whereas twin A showed normal growth, in twin B, all of the long bones appeared to be abnormally short (the long bone measurements with the femur measuring 11.6 mm, tibia 7.2 mm, humerus 11.5 mm, radius 7.9 mm, all compatible with <5th percentile). Curved femurs with a telephone-receiver-like appearance, short ribs, and a narrow thorax with prominent abdomen were also observed (). The femur length (FL)/abdominal circumference (AC) ratio was 0.12. The vertebral and skull ossification patterns were normal. No overt cloverleaf skull deformity was observed. The nasal bone was not visible but there are no other abnormalities in fetal face.\nThe couple was counseled about the increased risk of chromosomal abnormality or lethal TD. Thereafter, they decided to undergo an assessment of specific FGFR3 mutations by routine cytogenetic analysis. Amniocentesis of the twins performed during the 15th gestational week showed normal karyotypes (46, XY and 46, XY) for both babies. However, nucleotide sequence analysis of cDNA during the screen for mutations in FGFR3 for twin B revealed a C to T transition at nucleotide 742 (C742T) within exon 6. This heterozygous 742C->T (R248C) mutation in the FGFR3 causes an Arg248Cys (CGC->TGC) substitution. Molecular analysis of the same locus in twin A showed normal finding ().\nWe counseled the couple extensively, and explained that this genetic condition causes type-1 TD. Thereafter, they decided to proceed with selective fetal termination with the hope of proceeding with a normal singleton pregnancy. At the 19th gestational week, selective fetal termination was performed under ultrasonographic guidance using a 20-gauge needle and injection of potassium chloride into the fetal heart. The remainder of the pregnancy was uneventful and the patient delivered a healthy male infant weighing 3,575 g and a mummified, macerated fetus weighing 91 g during the 39th gestational week by Cesarean section due to persistent occiput posterior position.