Prenatal Diagnosis of Capillary Malformation-Arteriovenous Malformation Syndrome in a Dizygotic Twin Gestation

Document Type

Conference Proceeding

Publication Date

2026

Publication Title

Genetics in Medicine Open

Abstract

Treatment and Management: The patient opted to continue both pregnancies. Expectant management was pursued with serial ultrasound for hydrops assessment. At 30 weeks gestation, twin 1 was noted to have polyhydramnios, large pleural effusion, and bilateral renal pelvis dilatation. The patient continued hydrops assessment as well as antenatal surveillance at that time for both twins. Fetal hydrops in twin 1 ultimately developed at 32 weeks gestation. Given the poor prognosis for twin 1, counseling included options for ongoing surveillance of both fetuses with increased risk of prematurity for both twins or surveillance for twin 2 alone with increased risk of stillbirth for twin 1. The patient declined fetal surveillance or intervention for twin 1. Pediatric palliative care was consulted. Outcome and Follow-Up: At 33 weeks gestation, intrauterine fetal demise of twin 1 was diagnosed. Expectant management of the pregnancy with ongoing fetal surveillance of twin 2 was pursued. The patient presented at 35 weeks gestation in preterm labor. She ultimately had spontaneous vaginal delivery of twin 1 and primary cesarean delivery for twin 2 due to malpresentation. Discussion: This case demonstrated a de novo, pathogenic RASA1 variant in a discordant twin gestation, which ultimately resulted in fetal demise of the affected twin. This finding was identified through genome sequencing, which was pursued for prenatal ultrasound finding of a cystic hygroma with unrevealing karyotype and microarray. A case series and literature review that included 24 fetuses with CM-AVM reported a 25% risk of perinatal demise. Additionally, polyhydramnios (44%), pleural effusion (28%), and non-immune hydrops (24%) were seen in included cases. These findings were consistent with our case. Given the increased morbidity and mortality associated with this diagnosis, management in the setting of a twin gestation can prove to be challenging for both patients and providers. Conclusion: Genome sequencing offered the opportunity for prenatal diagnosis of CM-AVM following abnormal ultrasound. Though there is limited literature regarding prognosis and management of pregnancies affected by CM-AVM, available literature suggests a high risk of perinatal morbidity and mortality. Prognosis is of particularly high importance in the case of a twin gestation where management decisions can impact both the anomalous and non-anomalous fetus. This case highlights the need for further elucidation of prognostic factors for CM-AVM syndrome and the role of genome sequencing in prenatal diagnosis for cystic hygroma. Introduction: We present a unique case in which prenatal genome sequencing identified a pathogenic variant in the RASA1 gene, consistent with autosomal dominant capillary malformation-arteriovenous malformation syndrome (CM-AVM), in the setting of a dizygotic twin gestation. Literature regarding prenatal manifestations of CM-AVM syndrome is limited, primarily consisting of case reports and series. Management of this case was further complicated by a twin gestation with a non-anomalous second twin and development of hydrops in the affected twin. Case Presentation: A 30-year-old G1P0 presented to our Fetal Imaging unit at 11w2d gestation due to suspected cystic hygroma in twin 1 in the setting of a dichorionic-diamniotic twin gestation. On ultrasound at that time, a cystic hygroma was confirmed in twin 1. Prenatal cell-free DNA screening had been collected but results were not yet available. Diagnostic Workup: Chorionic villous sampling was performed from both placentas with karyotype and chromosomal microarray obtained for each sample. In both fetuses, the results were negative. Repeat ultrasound at 16 weeks gestation demonstrated resolution of the cystic hygroma. Following discussion with the patient, genome sequencing was pursued. Genome sequencing for twin 1 demonstrated a de novo, pathogenic 47.3 kb deletion within the region of chromosome 5q14.3, encompassing exons 2-9 of the RASA1 gene consistent with autosomal dominant CM-AVM.

Volume

4

Issue

Suppl 1

First Page

104279

Comments

2026 ACMG (American College of Medical Genetics) Clinical Genetics Meeting, March 10-14, 2026, Baltimore, MD

Last Page

104279

DOI

10.1016/j.gimo.2026.104279

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