Autopsy and Case Reports
Autopsy and Case Reports
Autopsy Case Report and Review

Novel autopsy and genetic findings in an acardiac twin: case report and literature review

Natalie Fabrizio; Christopher L. Pankey; Kathleen Martin; Michael Baker; Cameron Clark Felty

Downloads: 3
Views: 362


Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twinning whereby a donor twin perfuses an acardiac twin via aberrant vascular anastomoses. The resulting paradoxical retrograde blood flow supplying the acardiac twin is oxygen-poor, leading to some of the most severe malformations encountered in humans. Though the first descriptions of acardiac twins date back to at least the 16th century, the pathophysiologic processes which underpin the development of TRAP sequence are still being elucidated. Theories on the pathogenesis of TRAP sequence include deficiencies intrinsic to the embryo and primary abnormalities of the placental vasculature. Autopsy studies continue to provide clues to the underlying pathogenesis of TRAP sequence, and the characterization of the spectrum of manifestations that can be observed in acardiac twins. Herein, we present the clinical, autopsy, and molecular findings in a unique case of TRAP sequence. Novel findings include a primitive cloaca-like structure and chromosomal aberrations involving 6q11.1 and 15q25.1.


Fetofetal Transfusion, Cloaca, Twins Monozygotic, genetics, Chromosomal Aberrations


1 Kashireddy P, Larson A, Minturn L, Ernst L. Case report of autopsy and placental examination after radiofrequency ablation of an acardiac twin. Lab Med. 2015;46(3):248-53. PMid:26199267.

2 Bhatnagar KP, Sharma SC, Bisker J. The holoacardius: a correlative computerized tomographic, radiologic, and ultrasonographic investigation of a new case with review of literature. Acta Genet Med Gemellol (Roma). 1986;35(1-2):77-89. PMid:3529789.

3 James WH. A note on the epidemiology of acardiac monsters. Teratology. 1977;16(2):211-6. PMid:929437.

4 Botto LD, Feldkamp ML, Amar E, et al. Acardia: epidemiologic findings and literature review from the International Clearinghouse for Birth Defects Surveillance and Research. Am J Med Genet C Semin Med Genet. 2011 Nov 15;157C(4):262-73. PMID: 22002952.

5 Phelan MC, Hall JG. Acardia. In: Stevenson RE, Hall JG, editors. Human malformations and related anomalies. 2nd ed. New York: Oxford University Press; 2006. p. 1394-96.

6 Sceusa DK, Klein PE. Ultrasound diagnosis of an acardius acephalic monster in a quintuplet pregnancy. J Diagn Med Sonogr. 1990;6(2):109-12.

7 Weisz B, Peltz R, Chayen B, et al. Tailored management of twin reversed arterial perfusion (TRAP) sequence. Ultrasound Obstet Gynecol. 2004;23(5):451-5. PMid:15133794.

8 Chaliha C, Schwarzler P, Booker M, Battash M, Ville Y. Case report: Trisomy 2 in an acardiac twin in a triplet in-vitro fertilization pregnancy. Hum Reprod. 1999;14(5):1378-80. PMid:10325298.

9 Bolaji I, Mortimer G, Meehan F, England S, Greally M. Acardius in a triplet pregnancy: cytogenetic and morphological profile. Acta Genet Med Gemellol (Roma). 1992;41(1):27-32. PMid:1488853.

10 Kuran J, Niszczota C, Kolesnik A, Dangel JH. P23.15: monochorionic triamniotic triplet pregnancy complicated by twin reversed arterial perfusion (TRAP) sequence. Ultrasound Obstet Gynecol. 2012;40(S1):259.

11 Lattanzi W, De Vincenzo RP, De Giorgio F, Stigliano E, Capelli A, Arena V. An acephalus acardius amorphous fetus in a monochorionic pregnancy with sex discrepancy. Twin Res Hum Genet. 2006;9(5):697-702. PMid:17032553.

12 Malinowski W. Twin reversed arterial perfusion syndrome in historical sources. GinPolMedProject. 2019;1(51):31-9.

13 Remien K, Majmundar SH. Physiology, fetal circulation. USA: StatPearls Publishing; 2022.

14 Cheema SS. A case report of TRAP sequence with preeclampsia and review of literature. MJCMH. 2018;2(1):44-7.

15 Malone FD, D’alton ME. Multiple gestation: clinical characteristics and management. In: Creasy RK, Resnik R, Iams JD. Creasy and Resnick’s maternal fetal medicine: principles and practice. 5th ed. Philadelphia, PA: Elsevier; 2004. p. 654-75.

16 Lindsey SE, Butcher JT, Yalcin HC. Mechanical regulation of cardiac development. Front Physiol. 2014;5:318. PMid:25191277.

17 Benirschke K. The monozygotic twinning process, the twin-twin transfusion syndrome and acardiac twins. Placenta. 2009;30(11):923-8. PMid:19748667.

18 Martínez‐Frías ML, Group EW, ECEMC Working Group. Epidemiology of acephalus/acardius monozygotic twins: new insights into an epigenetic causal hypothesis. Am J Med Genet A. 2009;149A(4):640-9. PMid:19291778.

19 Das K. ACARDIACUS ANCEPS. BJOG. 1902;2(4):341-55.

20 Buyukkaya A, Tekbas G, Buyukkaya R. Twin reversed arterial perfusion (TRAP) sequence; characteristic gray-scale and Doppler ultrasonography findings. Iran J Radiol. 2015;12(3):e14979. PMid:26557268.

21 Gupta A, Bischoff A, Peña A, Runck LA, Guasch G. The great divide: septation and malformation of the cloaca, and its implications for surgeons. Pediatr Surg Int. 2014;30(11):1089-95. PMid:25217828.

22 Carlson BM. Digestive and respiratory systems and body cavities. In: Carlson BM. Human embryology and developmental biology. 2nd ed. United States: Elsevier; 1999. p. 341-83.

23 Lewitowicz P, Wincewicz A, Koziel D, et al. Acardius acephalus fetus-report of distinctive anatomical anomalies with regards to pathophysiology of TRAP sequence. Clin Exp Obstet Gynecol. 2015;42(6):814-8. PMid:26753494.

24 Healey MG. Acardia: predictive risk factors for the co‐twin’s survival. Teratology. 1994;50(3):205-13. PMid:7871485.

25 Kerr MG, Rashad MN. Autosomal trisomy in a discordant monozygotic twin. Nature. 1966;212(5063):726-7.

26 Scott JM, Ferguson‐Smith M. Heterokaryotypic monozygotic twins and the acardiac monster. J Obstet Gynaecol Br Commonw. 1973;80(1):52-9. PMid:4735250.

27 Rehder H, Geisler M, Kleinbrecht J, Degenhardt K. Monozygotic twins with 47, XXY karyotype and discordant malformations. Teratology. 1978;17:5a.

28 Deacon JS, Machin GA, Martin JM, Nicholson S, Nwankwo DC, Wintemute R. Investigation of acephalus. Am J Med Genet. 1980;5(1):85-99. PMid:7190356.

29 Bieber FR, Nance WE, Morton CC, et al. Genetic studies of an acardiac monster: evidence of polar body twinning in man. Science. 1981;213(4509):775-7. PMid:7196086.

30 Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol. 1983;7(4):285-93. PMid:6658475.

31 Shapiro L, Wilmot P, Duncan P, Davidian M, Fakhry J, Capone A, editors. Holoacardius acephalus: cytogenetic abnormalities as the principle pathogenetic mechanism. In: Proceedings Greenwood Genet Center; 1986; Greenwood. Greenwood, S.C.: The Center; 1986. p. 128.

32 Buehler B, McManus B, Mrocezek E. Acardiac monsters: clinical karyotypic and pathologic features. Teratology. 1986;33:44C.

33 Moore CA, Buehler BA, McManus BM, et al. Acephalus‐acardia in twins with aneuploidy. Am J Med Genet Suppl. 1987;28(S3):139-43. PMid:3130847.

34 Wolf H, MacDonald J, Bradford W. Holoacardius anceps with abnormal karyotype and multicystic renal dysplasia with patent ductus arteriosus in a surviving co-twin. Lab Invest. 1990;62(1): P10-P10.

35 Ginsberg NA, Applebaum M, Rabin SA, et al. Term birth after midtrimester hysterotomy and selective delivery of an acardiac twin. Am J Obstet Gynecol. 1992;167(1):33-7. PMid:1442950.

36 Fisk NM, Ware M, Stanier P, Moore G, Bennett P. Molecular genetic etiology of twin reversed arterial perfusion sequence. Am J Obstet Gynecol. 1996;174(3):891-4. PMid:8633663.

37 Blaicher W, Repa C, Schaller A. Acardiac twin pregnancy: associated with trisomy 2: case report. Hum Reprod. 2000;15(2):474-5. PMid:10655326.

38 Mihci E, Velagaleti GV, Ensenauer R, Babovic-Vuksanovic D. The phenotypic spectrum of trisomy 2: report of two new cases. Clin Dysmorphol. 2009;18(4):201-4. PMid:19474704.

39 McHenry A, Morotti R, Hui P. Placenta teratoma or acardiac fetus amorphous: a case study by DNA genotyping. Int J Gynecol Pathol. 2022;41(1):51-8. PMid:33770056.

40 Weiss M, Chithiwala Z, Karnezis A, Chien J, Hedriana H, Singh K. P640: Molecular findings of a placental mass in association with neonatal mosaic trisomy 21: Teratoma vs monozygotic acardiac amorphous twin. Genet Med Open. 2023;1(1 Suppl):100696.

41 Hu X, Li L, Zhang H, et al. Prenatal diagnosis of a de novo tetrasomy 15q24.3-25.3: case report and literature review. J Clin Lab Anal. 2020;34(7):e23288. PMid:32185823.

42 Zollino M, Tiziano F, Di Stefano C, Neri G. Partial duplication of the long arm of chromosome 15: confirmation of a causative role in craniosynostosis and definition of a 15q25‐qter trisomy syndrome. Am J Med Genet. 1999;87(5):391-4.<391::AID-AJMG4>3.0.CO;2-O. PMid:10594876.

43 Chen C-P, Chen C-Y, Chern S-R, et al. Molecular cytogenetic characterization of a duplication of 15q24. 2-q26. 2 associated with anencephaly and neural tube defect. Taiwan J Obstet Gynecol. 2017;56(4):550-3. PMid:28805617.

44 Hussein IR, Bader RS, Chaudhary AG, et al. Identification of de novo and rare inherited copy number variants in children with syndromic congenital heart defects. Pediatr Cardiol. 2018;39(5):924-40. PMid:29541814.

45 Hopkin R, Schorry E, Bofinger M, et al. New insights into the phenotypes of 6q deletions. Am J Med Genet. 1997;70(4):377-86.<377::AID-AJMG9>3.0.CO;2-Q. PMid:9182778.

46 Engwerda A, Frentz B, den Ouden AL, et al. The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports. Eur J Hum Genet. 2018;26(10):1478-89. PMid:29904178.

Submitted date:

Accepted date:

Publication date:

65e747d7a95395790d3a5ba3 autopsy Articles
Links & Downloads

Autops Case Rep

Share this page
Page Sections