Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant lipid disorder characterized by markedly elevated low-density lipoprotein (LDL) cholesterol, increased maternal cardiovascular risk, and a potential transgenerational impact.Twin pregnancies in women with FH are rarely reported, and management becomes more complex when cervical incompetence coexists.Prenatal genetic testing plays a crucial role in such high-risk gestations, particularly when fetal anomalies are identified.Case description: A 23-year-old primigravida, a known case of FH on atorvastatin prior to conception and with a history of multiple xanthoma excisions, conceived spontaneously and was confirmed to have a dichorionic diamniotic twin pregnancy.At 6 weeks of gestation, atorvastatin was discontinued, and cholestyramine was initiated.Early pregnancy was uneventful, with normal first-trimester screening.In the second trimester, an anomaly scan revealed bilateral congenital talipes equinovarus (CTEV) in twin A. Amniocentesis was performed: Quantitative fluorescence polymerase chain reaction (QF-PCR) excluded trisomies 13, 18, and 21 and confirmed a normal sex chromosome complement.Whole exome sequencing (WES) showed no variants explaining the talipes but identified a heterozygous likely pathogenic low-density lipoprotein receptor (LDLR) c.1567G>C (p.Val523Leu) variant, consistent with FH and suggestive of vertical transmission.At 30 +1 weeks, she was referred with ultrasonographic evidence of cervical incompetence and managed conservatively with progesterone, bed rest, antenatal corticosteroids, and surveillance.At 34 +2 weeks, she developed preterm premature rupture of membranes (PPROM) and underwent an emergency cesarean section for malpresentation.Intraoperatively, atonic postpartum hemorrhage was controlled with uterotonics, B-Lynch sutures, and bilateral uterine artery ligation.Twin A (2.225 kg, female) was breech with bilateral CTEV; twin B (2.125 kg, female) was phenotypically normal.Both neonates had good Apgar scores and brief neonatal intensive care unit (NICU) stays.Postpartum, the mother was restarted on atorvastatin and fenofibrate.Given the maternal diagnosis of FH and the identification of a likely pathogenic LDLR mutation, cascade screening was advised for the neonates.Early childhood lipid profile monitoring and genetic testing for the identified LDLR variant were recommended to enable timely preventive interventions.Conclusion: This case highlights the challenges of managing a twin pregnancy complicated by FH and cervical incompetence.Prenatal genetic testing identified a heritable LDLR mutation, underscoring the importance of cascade screening and long-term follow-up of offspring.Favorable outcomes were achieved with multidisciplinary, individualized care.
Sankar et al. (Fri,) studied this question.