Absent pulmonary valve syndrome is among the rarest of congenital cardiac anomalies. It is defined by the absence, or severe underdevelopment, of the pulmonary valve, the one-way gate that normally prevents blood from flowing backward from the pulmonary artery into the right ventricle. Without that valve, every heartbeat drives blood forward through a narrowed outflow tract and then lets it slosh backward in diastole, hammering the pulmonary arteries from both directions. The result is the condition’s signature finding: massive, sometimes aneurysmal dilation of the pulmonary arteries and their branches, which in the confined space of the fetal thorax can compress the airways and crowd out the surrounding structures. Precise incidence figures are difficult to pin down, but recent reviews suggest that absent pulmonary valve syndrome accounts for roughly 0.2 to 0.4 percent of all congenital heart disease, and that among fetuses diagnosed prenatally, more than 84 percent occur in association with tetralogy of Fallot, the classic conotruncal defect combining a ventricular septal defect, an overriding aorta, right ventricular outflow obstruction, and right ventricular hypertrophy.

The prognosis for fetuses diagnosed with this physiology before birth is sobering. In one series of 37 prenatally diagnosed fetuses, survival after initial diagnosis was only about 37 percent overall, with survival of roughly 30 percent for the tetralogy-associated variant. Against that backdrop, the new case report adds an unusual twist: the fetal heart was not only burdened by a suspected absent pulmonary valve but was also positioned abnormally, with dextrocardia, a rightward orientation of the cardiac apex within a normally positioned abdominal situs. Isolated dextrocardia of this kind is itself rare and is reported to be accompanied by complex intracardiac defects in the vast majority of cases, carrying a worse outlook than the mirror-image variety. The combination of a conotruncal malformation, absent pulmonary valve physiology, and dextrocardia in a single fetus is exceptionally uncommon, and the authors present it as a contribution to the limited literature on the prenatal natural history of this cluster of anomalies.

The mother was a 33-year-old woman in her second pregnancy, referred at 24 weeks of gestation for fetal cardiac evaluation. She carried a diagnosis of pre-gestational diabetes mellitus with demonstrably suboptimal glycemic control; her hemoglobin A1c at admission was 8.3 percent, well above the thresholds associated with elevated risk of fetal malformation. No additional maternal risk factors were identified. The referral triggered a comprehensive fetal echocardiographic workup using two-dimensional imaging, M-mode, color Doppler, and spectral Doppler, the full modern toolkit of prenatal cardiac diagnosis, and it is the meticulous serial documentation that gives this report much of its scientific value.

The initial scan at 24 weeks established the anatomy in detail. The fetal heart sat with a rightward apex, consistent with isolated dextrocardia. The main pulmonary artery was already markedly dilated, measuring 15 millimeters, and Doppler interrogation demonstrated both pulmonary stenosis and significant pulmonary regurgitation, with diastolic retrograde flow visible in the main pulmonary artery. The right ventricular free wall appeared hypertrophied, and imaging of the left ventricular outflow tract revealed a large subaortic ventricular septal defect with an overriding aorta, findings squarely compatible with a conotruncal anomaly on the tetralogy spectrum. Imaging of the pulmonary valve region showed only rudimentary ridges where normal leaflets should have been, the echocardiographic hallmark of the absent pulmonary valve variant. At that stage the fetus showed no signs of hydrops, and umbilical Doppler indices remained normal, suggesting that despite the severity of the anatomy, the circulation was still compensating.

What followed over the next four weeks was a documented unraveling of that compensation. Serial scans tracked the main pulmonary artery as it ballooned from 15 millimeters at 24 weeks to 18 millimeters at 26 weeks and 21 millimeters at 28 weeks. The cardiothoracic ratio, a measure of heart size relative to the chest, climbed from roughly 70 to 75 percent to as high as 80 percent, reflecting progressive biventricular hypertrophy and massive cardiomegaly. Doppler velocities across the stenotic, regurgitant pulmonary outflow rose in parallel. Then, at 27 weeks, the fetal echocardiogram revealed the development of hydrops fetalis, the accumulation of fluid in body cavities that signals decompensated cardiac failure. Bilateral pleural effusions appeared, followed by marked ascites. In structural fetal heart disease, the onset of hydrops is one of the most powerful adverse prognostic markers known, reflecting elevated central venous pressures and ventricular dysfunction, and reported series consistently show sharply increased fetal and neonatal loss once it supervenes.

Management options, the authors explain, were limited from the start. Given the complexity of the defects and the rapidly evolving hydrops, no intrauterine cardiac intervention was deemed feasible. The team instead pursued close surveillance with repeat echocardiography and intensive counseling of the parents about prognosis and potential perinatal outcomes. Despite maximal expectant management, the pregnancy ended at 30 weeks with intrauterine fetal demise secondary to progressive hydrops. Notably, by that point the mother’s HbA1c had improved to 6.6 percent, but the critical period of embryonic cardiac development had long since passed. Genetic assessment was incomplete: amniocentesis was not technically feasible because of the patient’s delayed presentation, although noninvasive prenatal testing had shown no evidence of trisomy 13, 18, or 21. The authors acknowledge that the absence of postmortem examination means the precise intracardiac anatomy, particularly the suspected absent pulmonary valve variant, could not be definitively confirmed, and that 22q11.2 deletion and other genetic contributors remain unassessed.

The mechanistic link to maternal diabetes is one of the most scientifically interesting dimensions of the case. Pre-gestational diabetes is a well-established, non-inherited risk factor for congenital heart disease, with particularly strong associations for conotruncal defects, exactly the spectrum observed here. The leading explanation involves hyperglycemia-driven oxidative stress during cardiac morphogenesis, the window in early pregnancy when the heart takes shape. Experimental models and human observational studies have repeatedly shown that elevated glucose impairs the survival and migration of cardiac neural crest cells, a transient embryonic cell population essential for septating the outflow tract and remodeling the aorticopulmonary structures, and disrupts endocardial cushion development. Population data reinforce the dose-response relationship: compared with normal HbA1c, values above 8 percent confer roughly a fourfold higher risk of major congenital heart disease, and even modest elevations above about 5.6 percent increase risk. Across large cohorts, pre-gestational diabetes raises the risk of all congenital heart defect subtypes, with the greatest excess for outflow-tract defects. Emerging work also suggests genetic modifiers, including reduced NOTCH1 function, that may render some fetuses more vulnerable to maternal hyperglycemia, hinting at a gene-environment interaction that could one day refine risk stratification.

For clinicians, the case is a pointed argument for targeted early fetal echocardiography, typically performed between 18 and 22 weeks and earlier when feasible, in pregnancies at elevated risk, including all those complicated by pre-gestational diabetes. Early diagnosis enables comprehensive anatomic and rhythm assessment, serial surveillance for evolving ventricular hypertrophy, outflow obstruction, and heart failure, genetic counseling and testing for conditions such as 22q11.2 deletion, and multidisciplinary delivery planning at tertiary centers. It also opens the door to realistic counseling: in published cohorts of fetal dextrocardia, most cases involve complex heart disease, and outcomes range widely depending on associated defects. But the deepest lesson of this report lies upstream of any scanner. Once hydrops appears in structural fetal heart disease, therapeutic options in utero are few, and outcomes deteriorate dramatically. The single most effective intervention to prevent cases like this one happens before conception, through tight glycemic control and maternal education. This fetus’s heart, imaged in such painful detail as it failed, stands as a vivid scientific case study and, equally, as a public health message: the fourfold elevated risk carried by an HbA1c above 8 percent is modifiable, and the time to modify it is months before a positive pregnancy test, not at 24 weeks when the heart has already formed and the damage is done.

Subject of Research: Prenatal diagnosis of suspected tetralogy of Fallot with absent pulmonary valve syndrome and dextrocardia in a pregnancy complicated by pre-gestational diabetes mellitus

Article Title: Coexistence of Suspected Tetralogy of Fallot With Absent Pulmonary Valve and Dextrocardia in Pre‐Gestational Diabetes Mellitus: A Case Report

Article References: Golbabaei, A., Kahani, V., & Mousivand, M. (2026). Coexistence of Suspected Tetralogy of Fallot With Absent Pulmonary Valve and Dextrocardia in Pre‐Gestational Diabetes Mellitus: A Case Report. Clinical Case Reports, 14(10), Article e73597. https://doi.org/10.1002/ccr3.73597

Image Credits: AI Generated

DOI: 10.1002/ccr3.73597

Keywords: tetralogy of Fallot, absent pulmonary valve syndrome, dextrocardia, pre-gestational diabetes, fetal echocardiography, congenital heart disease, hydrops fetalis, conotruncal defect, HbA1c, neural crest cells, intrauterine fetal demise, prenatal diagnosis