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

Situs inversus totalis is a congenital condition in which the major visceral organs are reversed from their normal positions along the left-right axis. The liver comes to lie predominantly on the left, the stomach and spleen shift to the right, and the cardiac apex points rightward, a configuration called dextrocardia. Estimates of its prevalence vary, but the condition is generally thought to affect roughly one in ten thousand individuals, and many carriers live their entire lives unaware of their mirrored anatomy. The condition arises during embryogenesis, when the normally stereotyped left-right patterning of the developing embryo is globally reversed. A landmark study by Nonaka and colleagues, published in Nature in 2002 and cited in the report’s reference list, demonstrated in the mouse embryo that the directional flow of fluid across the node, the embryonic organizer structure, is sufficient to determine left-right patterning, and that artificially reversing this flow reverses organ situs. Motile cilia at the node generate this leftward current, and defects in ciliary function underlie many cases of laterality disorders, including both situs inversus and the more chaotic arrangement known as heterotaxy.

As Sutherland and Ware summarized in their 2009 review of disorders of left-right asymmetry, the clinical significance of situs anomalies lies less in the mirroring itself than in its associations. Pure situs inversus totalis, in which the reversal is complete and orderly, is frequently an incidental finding discovered on imaging performed for unrelated complaints. Heterotaxy, by contrast, involves ambiguous or discordant organ positioning and is strongly associated with congenital heart disease and other malformations. A hospital-based study by Chen and colleagues published in Birth Defects Research in 2020 examined comorbidities in patients with situs inversus totalis and documented the range of conditions that accompany the mirrored anatomy in hospital populations. Clinicians must also contend with the practical consequences of reversed anatomy: physical examination findings are transposed, electrocardiograms require lead reversal for correct interpretation, appendicitis presents with left-sided pain, and surgical approaches must be rethought from first principles.

Into this already unfamiliar anatomical landscape, the Japanese team’s patient added a second layer of complexity. The case involves a patient found to have massive splenomegaly, an abnormal enlargement of the spleen, in the setting of malignant lymphoma, a cancer of the lymphatic system. The keywords attached to the published article situs inversus, malignant lymphoma, and splenomegaly capture the three threads of the story. In a body with normal organ arrangement, an enlarged spleen occupies the left upper quadrant of the abdomen and can be identified by its characteristic shape, its relationship to the ribs and stomach, and its homogeneous tissue density on computed tomography or ultrasound. In a patient with situs inversus totalis, the spleen resides on the right, and when it grows to enormous size it can extend across the midline, displace neighboring structures, and present an imaging appearance that mimics other organs.

The central image that gives the report its title shows a spleen so enlarged and so altered in texture that it resembled liver parenchyma. The phrase liver-like spleen refers to this visual deception: on cross-sectional imaging, the organ’s density and architecture appeared more like hepatic tissue than like the typical spleen. For clinicians evaluating a patient with reversed anatomy and a large right-sided or midline abdominal mass, distinguishing an enormously enlarged spleen from a displaced or accessory liver lobe, a tumor, or an abnormal collection of fluid is not a trivial exercise. The authors’ acknowledgment section thanks Dr. Ken Sadahira and Dr. Mikio Okayama for their assistance in patient care, indicating that the case was managed by a clinical team rather than observed from afar. The report also notes that no datasets were generated or analyzed, consistent with its format as a clinical image publication rather than a research study.

The association between lymphoma and the spleen is well established. The spleen is a lymphoid organ, and lymphomas, which arise from lymphocytes, frequently involve it. Splenomegaly in lymphoma may reflect direct infiltration by malignant cells, congestion, or reactive changes, and an enlarged spleen can itself be the presenting sign that brings a patient to medical attention. Trautner and colleagues, in a 2010 report in Clinical Nuclear Medicine cited by the Japanese authors, described the additional value of hybrid imaging in a patient with newly diagnosed lymphoma who also happened to have situs inversus totalis, underscoring that this combination of mirrored anatomy and hematologic malignancy, while rare, recurs often enough in the literature to merit attention. When the two coincide, the diagnostic radiologist must interpret every image against a reversed anatomical template, and subtle findings can be misassigned to the wrong organ.

Eitler, Bibok, and Telkes, writing in the International Journal of General Medicine in 2022, provided a clinical review of situs inversus totalis that frames the practical stakes. They emphasized that while most affected individuals are asymptomatic, the condition demands vigilance in diagnostic reasoning, surgical planning, and the interpretation of imaging studies. Their review, together with the earlier genetic and epidemiological work cited in the present case report, forms the scholarly backdrop against which the Kawasaki team’s images should be read. The report’s contribution is not a new therapy or a genetic discovery but a vivid demonstration of how far normal anatomical assumptions can mislead even experienced clinicians when the underlying blueprint is mirrored and then distorted by disease.

The publication process itself reflects the case’s timeline. According to the article’s record, the manuscript was received on 1 April 2026, accepted on 24 September 2026, and published on 1 October 2026 in the Journal of General Internal Medicine, the flagship journal of the Society of General Internal Medicine. All three authors are affiliated with Kawasaki Municipal Kawasaki Hospital in Kanagawa, Japan, with Okamoto based in the Department of Hematology and Miyaki and Kamiya in the Department of Internal Medicine, Kamiya holding appointments in both departments. Miyaki wrote the initial draft of the manuscript, and all authors had access to the data and helped revise the intellectual content. The authors declared no conflicts of interest and received no funding for the work. Correspondence for the article is directed to Takahiro Kamiya, whose ORCID identifier is listed in the publication record.

Why should a single clinical image merit attention beyond the ward? The answer lies in the pedagogical power of the exceptional case. Medical education proceeds in part through pattern recognition, and patterns are learned from typical presentations. But diagnostic error frequently occurs at the boundaries, where rare anatomy, rare disease, and rare combinations interact. A liver-like spleen in a patient with situs inversus totalis is precisely such a boundary case. It reminds radiologists that organ identification rests on more than position and density, that clinical history and correlative imaging are indispensable, and that the mirrored body can transform familiar signs into unfamiliar configurations. For internists and hematologists, it reinforces the point that splenomegaly in lymphoma can reach sizes and textures that confound standard heuristics.

The case also connects to one of the most elegant stories in developmental biology. The discovery that cilia-driven nodal flow sets the left-right axis, confirmed by the artificial flow experiments in mice, transformed laterality disorders from a descriptive curiosity into a mechanistically understood class of conditions. Every patient with situs inversus totalis carries in their anatomy the fossil record of that embryological decision, reversed at its origin. When disease such as lymphoma then remodels the reversed organs, clinicians are asked to read two overlapping stories at once: the congenital mirror and the acquired pathology. The image published by Miyaki, Okamoto, and Kamiya captures that intersection in a single frame, a spleen grown so large and altered that it borrowed the appearance of its mirrored neighbor, the liver. For the general reader, it is a striking reminder that human anatomy, even at its most orderly, holds surprises, and that medicine’s textbooks are at best maps of the average, to be consulted with humility whenever an individual patient departs from it.

Subject of Research: Splenomegaly resembling liver tissue in a patient with situs inversus totalis and malignant lymphoma

Article Title: A Liver-like Spleen in Situs Inversus Totalis

Article References: Miyaki, Y., Okamoto, S., & Kamiya, T. (2026). A Liver-like Spleen in Situs Inversus Totalis. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-026-10873-x

Image Credits: AI Generated

DOI: 10.1007/s11606-026-10873-x

Keywords: situs inversus, splenomegaly, malignant lymphoma, clinical imaging, left-right asymmetry, dextrocardia, heterotaxy, nodal cilia, hematology, diagnostic radiology, congenital anatomy, case report