After completing a pre-test and a brief atlas review, students were alternately assigned to study either CT images alone or CT images plus patient-specific 3D-printed models for 10 minutes. The researchers then administered the same written test covering normal abdominal anatomy and two congenital anomalies: choledochal cysts and anorectal malformations. A satisfaction survey followed the post-test. In the reported gain scores, the CT-plus-3D-printing group improved by 11.5%, compared with 7.2% in the CT-only group, a difference with a reported P value of 0.018.

Questions concerning the congenital anomalies showed greater improvement in the group that also used 3D-printed models, with a reported P value of 0.021. The abstract also reports that the additional 3D-printing assistance was particularly beneficial among students with lower baseline performance. Students rated the combined CT-plus-3D-printing module more highly for usefulness and overall satisfaction. These findings describe measured associations in this comparative study rather than demonstrating that 3D printing alone caused the improvements.

The results have important boundaries. The cohort was limited to 48 third-year medical students, and the groups did not differ significantly in their absolute post-test scores. In addition, the combined group received a greater volume and variety of learning material, including both CT images and 3D-printed models, while the comparison group used CT images alone. The authors therefore attribute the observed benefit to the combined multimodal approach rather than to 3D printing in isolation. The reported findings support further consideration of combined CT and 3D-printing materials in surgical clerkships, but the abstract does not establish the effectiveness of 3D printing independently or across other student populations and educational settings.

Subject of Research: Comparative evaluation of combined CT and 3D-printed abdominal anatomy teaching for medical students

Article Title: Application of 3D printing in medical anatomy education and its potential impact on student achievement

Article References: Yang, J., Youn, J. K., Ko, D., Yoon, H. B., & Kim, H.-Y. (2026). Application of 3D printing in medical anatomy education and its potential impact on student achievement. BMC Medical Education. https://doi.org/10.1186/s12909-026-10469-3

Image Credits: AI Generated

DOI: 10.1186/s12909-026-10469-3

Keywords: medical education, abdominal anatomy, 3D printing, computed tomography, medical students, congenital anomalies, multimodal learning, student achievement, Application, printing, medical, anatomy

Of the 44 exposed pregnancies, 32 resulted in live births. Two babies were born with major congenital anomalies: one ventricular septal defect and one hypospadias. This amounts to 2 of 32 live births, or 6.3%.

Five pregnancies ended in spontaneous abortion, including one case of fetal anencephaly, and seven pregnancies were terminated electively. These small numbers document observed outcomes but cannot determine whether JAK inhibitor exposure caused the anomalies or pregnancy losses. Neonatal assessments among the live births identified two preterm births at 36 weeks’ gestation, three infants small for gestational age and two newborns large for gestational age.

The authors concluded that current evidence is insufficient to establish or exclude an association between JAK inhibitor exposure and adverse fetal outcomes. They stated that potentially harmful effects cannot yet be ruled out, that routine use during pregnancy is not recommended, and that treatment should be approached with caution and a critical risk-benefit assessment until more data are available.

Subject of Research: Pregnancy outcomes following first-trimester exposure to JAK inhibitors

Article Title: Pregnancy outcome after first-trimester exposure to JAK inhibitors – an evaluation of the German Embryotox cohort

Article References: Habbel, A.-S., Beck, E., Mueller, A., & Dathe, K. (2026). Pregnancy outcome after first-trimester exposure to JAK inhibitors – an evaluation of the German Embryotox cohort. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01263-4

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01263-4

Keywords: JAK inhibitors, pregnancy safety, first-trimester exposure, congenital anomalies, fetal risk, baricitinib, upadacitinib, tofacitinib, filgotinib, German Embryotox, Pregnancy, outcome

The numbers matter because CAKUT is not a single disease but an umbrella term covering a spectrum of malformations that arise during fetal development of the kidneys, ureters, bladder and urethra. In the Senegalese cohort, malformations of the kidney itself accounted for 59.3 percent of cases, while malformations of the urinary tract accounted for 38.7 percent. These structural defects can obstruct urine flow, allow urine to reflux backward toward the kidney, or leave the organs with too little functioning tissue to filter blood effectively. Over years, the resulting mechanical and inflammatory damage destroys nephrons, the microscopic filtering units of the kidney, and the surviving nephrons compensate by working harder, a process called hyperfiltration that paradoxically accelerates further loss of function.

Chronic kidney disease in children is staged according to estimated glomerular filtration rate, or eGFR, a measure of how well the kidneys clear waste from the blood. Stage 1 and 2 disease may be silent for years, detectable only through laboratory abnormalities or imaging. By stage 4, eGFR has fallen below 30 milliliters per minute per 1.73 square meters of body surface area, and stage 5, kidney failure, marks the threshold at which kidney replacement therapy becomes necessary. The Senegalese researchers classified their patients using the KDIGO guidelines, the international standard developed by the Kidney Disease: Improving Global Outcomes initiative, allowing their results to be compared directly with cohorts from high-income countries.

One of the most sobering findings concerns timing. Antenatal diagnosis, the detection of urinary tract malformations on prenatal ultrasound before birth, was documented in only 7.7 percent of patients. In well-resourced health systems, routine second-trimester ultrasound screening frequently identifies hydronephrosis, the swelling of the kidney caused by urine buildup, while the fetus is still in the womb. That early signal allows pediatric urologists to plan interventions, from prophylactic antibiotics to corrective surgery, in the first weeks of life, often before a single infection has occurred. In the Senegalese cohort, the overwhelming majority of children were identified only after birth, and in many cases presumably only after symptoms had already appeared, meaning the malformations had months or years to inflict cumulative damage on developing kidneys.

The study’s strongest statistical signal involved infection. Urinary tract infections occurred in 13.9 percent of the children, and after adjusting for other clinical variables using logistic regression, the presence of a urinary tract infection tripled the odds of progressing to advanced chronic kidney disease, with an adjusted odds ratio of 3.02 and a 95 percent confidence interval of 1.29 to 7.08. The biological explanation is well understood. In a urinary tract already distorted by malformation, bacteria can ascend and colonize the kidney, triggering pyelonephritis, an infection of the renal tissue itself. Each episode of pyelonephritis leaves scar tissue in its wake, and renal scarring permanently reduces filtering capacity. In children with obstructive or refluxing malformations, infection and structural damage form a vicious cycle in which each worsens the other.

Access to definitive treatment emerged as another critical theme. Among the 31 children in the cohort who had a surgical indication, meaning a malformation that could and should have been corrected operatively, only 16, or 51.6 percent, actually underwent operative management. The study does not detail the reasons for this gap, but the authors point to limited access to timely specialized management as a likely contributor to kidney deterioration. Corrective surgery for CAKUT, whether relieving an obstruction at the junction between kidney and ureter, reimplanting a refluxing ureter into the bladder, or repairing posterior urethral valves, is time-sensitive. Delay allows ongoing pressure injury and recurrent infection to erode renal function that surgery alone cannot restore.

The implications extend beyond Senegal. CAKUT accounts for roughly 40 to 50 percent of pediatric end-stage kidney disease in most registries worldwide, and the burden falls disproportionately on low- and middle-income countries, where diagnostic infrastructure, pediatric nephrology services and kidney replacement therapy are scarce. Dialysis for children is expensive, technically demanding and often unavailable outside capital cities, and pediatric transplantation rates in sub-Saharan Africa remain among the lowest in the world. A child who reaches end-stage kidney disease in a setting without sustainable access to kidney replacement therapy faces a grim prognosis, which makes preventing progression through early detection and infection control not merely desirable but potentially lifesaving.

The retrospective design of the study carries inherent limitations that the authors acknowledge. Because the analysis relied on medical records from a single tertiary referral center, it captures children who reached specialized care, potentially missing those who died or deteriorated before referral, which could mean the true burden of advanced disease is even higher. Missing data on antenatal screening, laboratory values and follow-up duration are common in retrospective cohorts drawn from resource-limited settings, and the logistic regression can adjust only for variables that were reliably recorded. Still, the sixteen-year span and the size of the cohort make this one of the most substantial datasets on pediatric CAKUT from the region, and the consistency of the infection signal with findings from other settings strengthens its credibility.

The authors’ conclusion is a call for structural change rather than a single clinical fix. They argue that strengthening early detection, through wider antenatal ultrasound coverage and postnatal screening of at-risk infants, combined with structured follow-up strategies, is essential to mitigate progression in resource-limited settings. In practical terms, that means training more sonographers to recognize fetal urinary tract dilatation, ensuring that newborns with identified malformations receive timely postnatal imaging and antibiotic prophylaxis where indicated, building referral pathways so that infants reach pediatric surgical services before infections accumulate, and establishing long-term surveillance of kidney function so that progression is caught at reversible stages. Each of these steps is far cheaper than a lifetime of dialysis, and each addresses a point in the disease trajectory where the Senegalese data show the system currently losing children.

For the global nephrology community, the study adds weight to a growing consensus that the pediatric chronic kidney disease burden in sub-Saharan Africa is driven less by biology than by systems. The same malformations that progress to kidney failure in Dakar are frequently corrected in infancy in Europe or North America, with most children retaining adequate kidney function into adulthood. The difference lies in when the anomaly is found, how quickly infections are treated, and whether corrective surgery is performed in time. The Senegalese cohort, with nearly one in five children reaching advanced disease and more than one in ten reaching kidney failure, quantifies precisely what is at stake when those steps are delayed, and it provides a baseline against which future improvements in screening, surgical access and follow-up can be measured.

Subject of Research: Progression to advanced chronic kidney disease among children with congenital anomalies of the kidney and urinary tract in Senegal

Article Title: Advanced chronic kidney disease in children with CAKUT: a retrospective cohort study in Senegal

Article References: Cissé, L., Lo, F. B., Mbaye, P. A., Guèye, D., Ndoye, M., Ndiaye, G., Ndongo, A., Keïta, Y., Ndoye, N. A., Ndour, O., Sylla, A., & Ngom, G. (2026). Advanced chronic kidney disease in children with CAKUT: a retrospective cohort study in Senegal. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07458-2

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07458-2

Keywords: CAKUT, chronic kidney disease, pediatric nephrology, Senegal, urinary tract infection, congenital anomalies, end-stage kidney disease, KDIGO, antenatal diagnosis, low-resource settings, retrospective cohort, pediatric surgery

The research team conducted the study in 2022 at the Upper East Regional Hospital, using a qualitative phenomenological design known as Interpretative Phenomenological Analysis, or IPA. Unlike survey-based approaches that measure prevalence or quantify stress scores, IPA is built to excavate the texture of personal experience. Researchers conduct in-depth interviews, then systematically analyze transcripts to identify how participants make sense of what has happened to them. The method is particularly suited to questions where meaning, not frequency, is the object of study: how a mother interprets her child’s condition, what she believes caused it, and whom she blames or forgives for it.

What emerged from the analysis was a picture in which cultural belief systems function as a kind of interpretive operating system for the mothers involved. Congenital anomalies, which are structural malformations that develop in utero, were frequently attributed to spiritual causes rather than biomedical ones. This attribution was not merely an intellectual position; it had material consequences. For some mothers, the spiritual framing invited stigma from their communities, compounding the practical difficulties of raising a child with complex medical needs. For others, the same spiritual framework became a source of coping strength, a way to make sense of an otherwise inexplicable event and to find meaning in the caregiving role.

The study’s findings on gender roles are perhaps its most pointed contribution to the global literature on caregiver burden. While the challenges faced by caregivers of children with congenital anomalies have been researched extensively worldwide, the authors note that limited work has examined how that experience depends on the specific sociocultural environment, particularly through the intersecting perspectives of religion, gender, and culture. In the Upper East Region, caregiving fell predominantly on mothers, producing emotional strain that was intensified by limited spousal support. Fathers, in the accounts analyzed, were largely absent from the day-to-day labor of care, a pattern consistent with broader findings in global health research on the gendered distribution of unpaid caregiving in many parts of sub-Saharan Africa.

This gendered asymmetry matters clinically, not just sociologically. Caregiver burden in pediatric congenital anomaly contexts is associated with maternal mental health outcomes, treatment adherence, and the consistency of follow-up care that children with chronic structural conditions require. A mother who is simultaneously navigating community stigma, managing appointments and medications alone, and absorbing the emotional weight of a diagnosis without a partner’s support is operating under conditions that health systems rarely account for when they design pediatric services. The study’s authors argue that this is precisely why culturally sensitive support programmes are needed rather than generic caregiver interventions imported from other contexts.

Religious belief emerged as a third, interlocking force in the mothers’ experiences. Faith shaped how mothers coped with their children’s conditions and how they made care decisions, but it sometimes brought them into direct conflict with medical advice. The study does not frame this as a simple clash between tradition and science; rather, it documents how religious frameworks provided genuine psychological resources for endurance while simultaneously creating decision-making pathways that could diverge from clinical recommendations. For health workers in the region, this means that effective communication with mothers requires understanding the religious logic behind their choices, not simply correcting it.

The methodological choice to use IPA rather than a quantitative burden scale is significant for what it allows the study to capture. Because the analysis centers on how mothers themselves interpret their situations, it surfaces contradictions that standardized instruments tend to flatten. The same cultural belief system that stigmatized one mother strengthened another. The same religious conviction that guided one mother toward acceptance led another to decline a recommended intervention. These variations, which the researchers identified as commonalities alongside unique differences across participants, are exactly the kind of findings that population-level surveys are structurally unable to detect.

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, with ethical clearance obtained from the Regional Health Directorate under approval number GHS/UE/RS/11/001 before data collection began. Participation was voluntary, respondents were given full information about the study’s purpose, and participants retained the right to withdraw at any point. The authors declare no competing interests and note that the research received no external funding. Artificial intelligence tools were used only for language editing and readability, with all intellectual content, interpretation, analysis, and conclusions remaining the responsibility of the authors.

The research team spans multiple Ghanaian institutions, reflecting the interdisciplinary nature of the question. Adongo is based in the Department of Public Health Education at the University of Skills Training and Entrepreneurial Development in Mampong-Ashanti. Vincent de Paul Kanwetuu brings a sociological perspective from the Department of Sociology and Social Work at Kwame Nkrumah University of Science and Technology in Kumasi. Dominic Nabil Bodpii is affiliated with the School of Business at the University for Development Studies in Tamale, Robert Kuchengye Mokulogo with the University of Business and Integrated Development Studies in Wa, and James Akazili with the School of Public Health at the University of Technology and Applied Sciences in Navrongo. This composition signals that the authors view maternal caregiving not as a narrow clinical problem but as one sitting at the intersection of public health, sociology, and development studies.

The study’s implications reach beyond the Upper East Region. Congenital anomalies occur globally, and the caregiver burden they generate is a recognized challenge in health systems everywhere. But the Ghanaian findings underscore a point that global health researchers have increasingly emphasized: the experience of caregiving is not universal. It is filtered through local beliefs about causation, local expectations about who bears responsibility for a child’s wellbeing, and local religious frameworks that define what acceptance and action look like. For practitioners, the authors conclude that empathetic, culturally sensitive approaches are essential for supporting mothers within this distinct sociocultural setting. For researchers, the study demonstrates that phenomenological methods remain a powerful tool for surfacing the lived realities that shape health outcomes long before any clinical measurement begins.

Subject of Research: Mothers' lived experiences caring for children with congenital anomalies in Ghana's Upper East Region

Article Title: Lived experiences of mothers caring for children with congenital anomalies at the Upper East Regional Hospital, Ghana: an interpretative phenomenological analysis

Article References: Adongo, A. A., Kanwetuu, V. D. P., Bodpii, D. N., Mokulogo, R. K., & Akazili, J. (2026). Lived experiences of mothers caring for children with congenital anomalies at the Upper East Regional Hospital, Ghana: an interpretative phenomenological analysis. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07593-w

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07593-w

Keywords: congenital anomalies, maternal caregiving, Ghana, interpretative phenomenological analysis, sociocultural factors, disability stigma, gender roles, religious belief, BMC Pediatrics, qualitative research, Upper East Region, caregiver burden

The urachus is a fibromuscular tubular structure that links the dome of the bladder to the umbilicus, derived from the cloaca and allantois during embryonic development. In most people it obliterates in infancy, collapsing into the fibrous median umbilical ligament. When that obliteration fails, a spectrum of anomalies results: a patent urachus accounts for roughly half of all urachal malformations, urachal sinuses about 15 percent, vesicourachal diverticula 3 to 5 percent, and urachal cysts around 30 percent. These remnants are usually silent, but they can become complicated by infection, malignant transformation, or, as in this case, stone formation. Urachal calculi are exceptionally rare, and their clinical and radiological appearances overlap with bladder calculi, vesicourachal diverticula, infected urachal cysts, and calcified urachal tumors, creating what the authors describe as a genuine diagnostic pitfall.

The patient’s story began with more than six months of intermittent, dull lower abdominal pain. The pain did not radiate and bore no relationship to urination. He denied urinary frequency, urgency, dysuria, blood in the urine, lumbar pain, fever, chills, and any discharge from the umbilicus. At a local hospital, cystoscopy had revealed bladder inflammation but no stone, a negative finding that would later prove misleading. On admission, the umbilicus appeared entirely normal, with no discharge, erythema, or visible sinus, and physical examination showed only mild suprapubic tenderness without a palpable mass. Laboratory work was similarly unrevealing: urinalysis showed red blood cells but no pyuria, urine culture was negative, procalcitonin measured just 0.061 ng/mL, and interleukin-6 and C-reactive protein were not elevated.

The turning point came with computed tomography. Non-contrast CT demonstrated a 1.2 by 0.9 centimeter densely calcified nodular lesion at the anterior bladder wall near the dome, with an attenuation of approximately 1112 Hounsfield units, a value firmly in the territory of true calculus rather than soft tissue. The lesion appeared to lie within the bladder outline, and no separate diverticular neck was identified on the available images. That combination, a midline calcification that looked intravesical but lacked any visible tract or neck, initially suggested a bladder diverticular calculus. The authors note that urachal stones are rare, have diverse clinical manifestations, and are easily misdiagnosed or missed entirely.

Definitive answers came only in the operating room. After preoperative evaluation and informed consent, the team performed combined transurethral and laparoscopic surgery under general anesthesia. Repeat cystoscopy systematically evaluated the bladder neck, trigone, ureteric orifices, lateral walls, anterior wall, and dome, and this time identified a calculus at the junction of the bladder dome and anterior wall, with an intravesical component and a residual component embedded in the urachal tract. Holmium laser lithotripsy was used to fragment and remove the visible intravesical portion. Because the residual stone was embedded within the urachus in an inaccessible location, and because of concerns about potential recurrence and malignant transformation, the surgeons converted to laparoscopic resection. A cord-like urachal remnant was identified at the bladder dome, the embedded calculus was palpable within the tract, and the involved remnant, residual stone, and a cuff of the bladder dome were excised en bloc with an ultrasonic device before the bladder was closed.

Histopathological examination confirmed a urachal remnant associated with calculus formation and inflammation, with no intestinal metaplasia, dysplasia, or malignancy, a reassuring result given that urachal remnants carry a recognized risk of cancerous transformation. Recovery was swift: the urinary catheter was removed on postoperative day 2, and the patient was discharged after a 7-day hospitalization. However, the follow-up story is incomplete. The patient was subsequently lost to follow-up, no post-discharge imaging or cystoscopy was available, and his symptom status and recurrence risk could not be assessed, a limitation the authors acknowledge candidly.

To place the case in context, the team conducted a structured search of PubMed updated through 18 July 2026, using combinations of terms including urachal stone, urachal calculus, urachovesical calculus, vesicourachal diverticulum, and urachal calcification, and screening reference lists of relevant reports. Because of heterogeneous terminology and incomplete reporting, they treated the effort as a structured literature review rather than a systematic review. The comparison with previously published cases is instructive. A 1994 report described a 59-year-old man with lower abdominal pain and radiopaque suprapubic shadows whose stone sat in a urachal sac near the anterior bladder; he remained asymptomatic four years after excision. A 2002 case involved a 55-year-old man with irritative voiding symptoms whose CT showed a midline urachal tract containing a cylindrical calculus extending into the bladder as a pedunculated stone, treated with combined endoscopic and laparoscopic removal. Other reports have described an inflamed urachal cyst containing multiple calculi in an adult woman, a vesicourachal diverticulum with a stone in a 24-year-old man, urachal remnant calcification discovered incidentally on trauma imaging, and an infected urachal sinus with a de novo stone presenting with fever and localized peritonitis in a young athlete.

What distinguishes the present case, the authors argue, is the combination of an atypical symptom profile and a misleading anatomical appearance, rather than the surgical technique alone. Unlike the 2002 patient whose CT revealed an obvious midline tract, this patient had isolated intermittent lower abdominal pain with no lower urinary tract or umbilical symptoms, and an initially negative cystoscopic examination. The calcification appeared to lie within the bladder outline without an obvious tubular tract or diverticular neck, creating a realistic risk of misclassification as a bladder diverticular stone. Epidemiologically, urachal abnormalities are rare congenital anomalies with an incidence of approximately 2 per 100,000 hospitalized adults, and while urachal cysts and urachal carcinoma represent the most common urachal pathologies in adults, urachal calculi are exceptionally rare. Their formation is thought to result from prolonged retention of residual urine within the urachal tract, combined with repeated urine reflux, urinary tract inflammation, epithelial cell shedding, and urate deposition; the relatively narrow lumen of urachal remnants and an alkaline urinary environment may further promote stone formation and growth.

The differential diagnosis of a densely calcified lesion at the anterior bladder wall includes several entities that demand careful separation. Bladder diverticular stones share the location and calcified density but sit within a diverticulum that communicates with the bladder lumen, and such stones are typically mobile, changing in size after voiding on CT. Distal ureteral stones produce peri-bladder calcified lesions but are accompanied by proximal ureteral dilatation and hydronephrosis, and lie along the ureteral course rather than in the midline. Urachal carcinoma with calcification presents as a midline supravesical mass with a soft tissue component that enhances, irregular margins, and calcification within the tumor matrix. Urachal cysts or infections produce midline supravesical lesions with cystic or inflammatory components, wall thickening, and surrounding fat stranding. In this case, the key distinguishing features were the midline location at the bladder dome, the very high CT attenuation of 1112 HU consistent with a calculus rather than tumor calcification, the absence of soft tissue enhancement on contrast CT, and intraoperative confirmation that the stone was embedded at the base of the urachus.

For diagnosis, ultrasonography can identify a fixed echogenic focus with posterior acoustic shadowing and may reveal a cystic remnant, while CT provides a broader assessment of the lesion’s relationship to the bladder dome, the median umbilical ligament, surrounding soft tissue, and any enhancing component. Sagittal and coronal reformations are particularly useful when axial images make a lesion appear intravesical, a point the authors emphasize as central to avoiding the misdiagnosis seen here. Cystoscopy remains important for assessing the bladder mucosa and any intravesical component, but a small lesion at the anterior dome can be overlooked, so systematic inspection of the dome and correlation with cross-sectional imaging are essential. Management should be individualized according to symptoms, infection, communication with the bladder, the possibility of malignancy, and the extent of the remnant. Symptomatic or complicated adult urachal remnants are commonly managed by excision, often with a bladder cuff when the lesion involves the dome, and transurethral lithotripsy alone may remove an exposed intravesical component while leaving an embedded calculus and the underlying remnant in place. Published outcomes after removal of the calculus and treatment of the underlying abnormality are generally favorable, though the small number of heterogeneous cases does not permit a reliable recurrence rate. The authors’ conclusion is straightforward: a midline calcification at the bladder dome should prompt consideration of a urachal origin even when it appears intravesical, and a high index of clinical suspicion, careful multiplanar CT evaluation, thorough cystoscopic examination, and histological evaluation of the excised remnant remain essential for accurate diagnosis and complete management.

Subject of Research: Diagnosis and surgical management of a rare urachal calculus with an atypical intravesical CT appearance

Article Title: Case Report: Urachal calculus with an atypical intravesical CT appearance and literature review

Article References: Long, X., Zhi, Y., Zhou, Y., Wang, D., & Guo, H. (2026). Case Report: Urachal calculus with an atypical intravesical CT appearance and literature review. Frontiers in Urology, 6, Article 1899074. https://doi.org/10.3389/fruro.2026.1899074

Image Credits: AI Generated

DOI: 10.3389/fruro.2026.1899074

Keywords: urachal calculus, urachus, bladder dome, computed tomography, cystoscopy, holmium laser lithotripsy, laparoscopic partial cystectomy, urachal remnant, differential diagnosis, urology, case report, congenital anomalies

The research team, led by Huiyun Ding and Weishun Lan of the Maternal and Child Hospital of Hubei Province in Wuhan, together with colleagues in Tangshan and the hospital’s own pathology department, reviewed every case of intestinal duplication that had been imaged by fetal MRI between September 2018 and May 2025 and later confirmed postnatally. Confirmation was not left to impression alone: each lesion was verified surgically and classified pathologically after birth. This design matters because prenatal imaging studies of rare congenital anomalies frequently rely on imaging findings alone, leaving open the possibility that some of the lesions described were never actually duplications at all. By anchoring every MRI feature to a pathologically verified diagnosis, the study provides an unusually solid evidentiary foundation for its descriptive claims.

The thirty-six fetuses underwent MRI at gestational ages ranging from twenty-six to thirty-nine weeks, a window late enough in pregnancy for fetal anatomy to be resolved in detail. Twenty-one of the fetuses were female and fifteen were male, a distribution that reflects the slight female predominance often noted for this anomaly. In the overwhelming majority of cases, thirty-one of thirty-six, or 86.1 percent, the duplication was an isolated finding, with no other structural malformations detected. The remaining five fetuses, 13.9 percent, carried additional anomalies, a reminder that enteric duplications can occur as part of broader developmental disturbances even when most appear alone.

On imaging morphology, the lesions split into two broad categories. Twenty-nine cases, 80.6 percent, appeared cystic, while seven cases, 19.4 percent, were tubular. This distinction is more than cosmetic. Cystic duplications behave as discrete fluid-filled masses that can exert mass effect on neighboring structures, whereas tubular duplications often run along a segment of bowel and may communicate with the intestinal lumen, sometimes causing obstruction, bleeding, or inflammation after birth. Postnatal surgical pathology added a second axis of classification: ten cases, 27.8 percent, were intraluminal, meaning the duplication lay within the bowel lumen itself, while twenty-six cases, 72.2 percent, were extraluminal, sitting outside the lumen as a separate cystic structure adjacent to the intestine.

Perhaps the most striking statistic in the study concerns location. Twenty-eight of the thirty-six lesions, 77.8 percent, were found in the ileum or ileocecal region, the distal portion of the small intestine where it meets the colon. The remaining lesions were scattered across the digestive tract: one in the duodenum, three in the jejunum, one in the ascending colon, and three in the descending colon. This distal small bowel predominance is consistent with the embryology of enteric duplications, which are thought to arise from errors in intestinal recanalization, abnormal persistence of the neurenteric canal, or partial twinning of the gut during early development. Whatever the precise mechanism, the practical implication for prenatal imaging is clear: a well-defined cystic mass on the mesenteric side of the distal ileum should immediately place enteric duplication high on the differential diagnosis.

The characteristic MRI appearance described by the authors follows a consistent pattern. The lesions present as well-defined, unilocular cystic masses within the fetal abdomen, showing homogeneous long T1 and long T2 signals on conventional sequences. In the language of MRI physics, long T1 means the fluid content appears dark on T1-weighted images, while long T2 means it appears bright on T2-weighted images, the classic signature of simple or near-simple fluid. This signal profile helps distinguish duplications from lesions containing blood products, fat, or calcification, which produce different combinations of T1 and T2 signal. The cyst walls, however, are not thin and delicate: the study emphasizes that duplications exhibit a thick wall, a feature that reflects their genuine intestinal lining, complete with mucosa and muscular layers, rather than the thin serosal covering of a simple mesenteric cyst.

The relationship between the cyst and the adjacent bowel emerged as a defining feature. The lesions were locally either sharing a common wall with the neighboring intestine or directly continuous with it, and they consistently sat on the mesenteric side of the bowel, in close contact with the intestinal wall. This mesenteric location is a key discriminator: many other abdominal cystic lesions in the fetus, such as ovarian cysts in female fetuses or meconium pseudocysts, do not share this intimate anatomical relationship with the bowel. The morphology itself proved variable, appearing as round, oval, tubular, bilobed, or even multilocular cysts, and the lesions could exert mass effect on adjacent bowel loops, a finding that may presage postnatal complications such as obstruction or volvulus.

Why does this descriptive catalog matter for clinical practice? Prenatal counseling depends heavily on what the imaging suggests. A lesion correctly identified as an enteric duplication allows the clinical team to plan delivery at an appropriate facility, arrange postnatal surgical evaluation, and counsel parents about a condition that is generally amenable to complete surgical resection with an excellent prognosis. A misdiagnosis, by contrast, can lead to inappropriate expectations, unnecessary anxiety, or missed planning for associated anomalies. The authors argue that systematic evaluation of four elements on fetal MRI, the relationship to the bowel, the size of the lesion, its morphology, and its signal characteristics, is crucial for accurate prenatal diagnosis and for distinguishing duplications from the long list of conditions that can mimic them.

The study also illustrates the complementary roles of ultrasound and MRI in fetal abdominal imaging. Ultrasound remains the first-line tool for detecting cystic abdominal masses in fetuses, but its ability to characterize wall thickness, tissue composition, and precise anatomical relationships is limited by acoustic windows and operator dependence. MRI, with its multiplanar capability and superior soft tissue contrast, can resolve features that ultrasound cannot, such as the thick cyst wall, the shared wall with adjacent bowel, and the homogeneous fluid signal within the lesion. The late gestational timing of the MRI examinations in this cohort, from twenty-six weeks onward, reflects the practical reality that many duplications are detected or further characterized in the third trimester, when the lesion has grown large enough to be conspicuous.

For a condition that affects an estimated one in several thousand live births, enteric duplication has long suffered from a paucity of systematically collected, pathologically anchored imaging data. This study, funded by the Joint Funding Program of Hubei Provincial Health Commission and conducted under ethics approval from the Maternal and Child Hospital of Hubei Province, adds a carefully described dataset to that literature. Its findings, that duplications are typically isolated, cystic, extraluminal, located in the ileocecal region, and characterized by a thick wall sharing a common boundary with the adjacent bowel on the mesenteric side, give radiologists a concrete checklist for the prenatal evaluation of fetal abdominal cysts. As fetal MRI becomes more widely available, the ability to recognize these signatures before birth may translate into better counseling, better surgical planning, and better outcomes for the children who carry these hidden duplications of the gut.

Subject of Research: Prenatal MRI features of pathologically confirmed fetal enteric duplication cysts

Article Title: Descriptive analysis of prenatal MRI features of pathologically confirmed enteric duplication cysts

Article References: Ding, H., Lan, W., Yang, W., Zuo, B., Yang, X., Liu, F., & Hong, Y. (2026). Descriptive analysis of prenatal MRI features of pathologically confirmed enteric duplication cysts. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07861-9

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07861-9

Keywords: fetal MRI, enteric duplication cyst, prenatal diagnosis, BMC Pediatrics, congenital anomalies, pediatric radiology, ileocecal duplication, abdominal cysts, Descriptive, analysis, prenatal, features

The research, published as an open-access article in BMC Pediatrics, was carried out by a team led by pediatric urology specialists at Hainan Women and Children’s Medical Center in Haikou, with additional participation from the Children’s Hospital of Fudan University in Shanghai. Between 2019 and 2021, the investigators retrospectively enrolled women who had delivered newborns with hypospadias at Hainan Maternal and Child Health Hospital as cases, while randomly selecting mothers of normal newborn male infants as controls. The final analysis included 96 infants with hypospadias and 480 male controls, a one-to-five matching ratio that gives the study reasonable statistical power for a single-center investigation.

Methodologically, the team relied on archived clinical records for maternal demographic and clinical characteristics, with the underlying information originally gathered through face-to-face or telephone communication as part of routine clinical care. Birth outcomes and maternal complications were verified directly from medical records, a step intended to reduce recall bias, a persistent weakness in retrospective case-control designs. Because the study was a secondary analysis of de-identified archived data, the hospital’s ethics committee formally waived the requirement for written informed consent, and the work was conducted in accordance with the principles of the Declaration of Helsinki. The statistical backbone of the analysis was multivariable conditional logistic regression, a technique well suited to matched case-control data because it allows researchers to estimate the independent effect of each exposure while holding other measured variables constant.

The results are striking for what they did not find. Maternal weight before pregnancy, weight gain during pregnancy, body mass index at delivery, maternal age, and infection with hepatitis B virus all showed no association with hypospadias in offspring. This is notable because maternal pre-pregnancy BMI, gestational weight gain, BMI at delivery, and gestational diabetes mellitus have all been proposed as modifiable factors independently linked to the condition, yet previous studies have reported mixed and sometimes contradictory results. The Hainan findings suggest that some of these commonly hypothesized metabolic pathways may not withstand scrutiny, at least in this population, and that the search for modifiable risk factors may need to look elsewhere.

Where associations did emerge, they clustered around maternal pregnancy complications and fetal characteristics. Maternal education showed a strong inverse relationship with hypospadias: compared with the reference group, higher education levels carried adjusted odds ratios of 0.35 (95 percent confidence interval 0.18 to 0.68) and 0.18 (95 percent confidence interval 0.07 to 0.50), meaning that children of more highly educated mothers were substantially less likely to be represented among the cases. Whether this reflects genuine biological protection, differences in health care access, nutritional patterns, or unmeasured confounding remains an open question that the authors themselves frame as hypothesis-generating rather than definitive.

Among the maternal complications, three stood out with particularly large effect sizes. Gestational hypertension was associated with an adjusted odds ratio of 6.27 (95 percent confidence interval 2.44 to 16.13), while intrahepatic cholestasis of pregnancy, a liver disorder characterized by impaired bile flow that typically presents with intense maternal itching, carried an adjusted odds ratio of 13.86 (95 percent confidence interval 3.00 to 64.03). Most dramatic of all was maternal hypothyroidism, with an adjusted odds ratio of 16.63 (95 percent confidence interval 5.01 to 55.20). The thyroid connection is biologically plausible: thyroid hormones play a role in fetal growth and development, and disruptions to the maternal endocrine milieu during the critical window of genital development in the first trimester have long been theorized to interfere with normal urethral fold fusion, the embryological process whose failure produces hypospadias.

On the fetal side, two factors were independently associated with the anomaly. Birth weight showed the largest effect in the entire study, with an adjusted odds ratio of 19.07 (95 percent confidence interval 6.58 to 55.25), and multiple gestation, meaning twin or higher-order pregnancies, carried an adjusted odds ratio of 7.89 (95 percent confidence interval 1.05 to 59.48). Both findings fit with a broader pattern in the hypospadias literature linking altered fetal growth and placental insufficiency to the malformation. Low birth weight and multiple pregnancies are both markers of a stressed intrauterine environment, and some researchers have proposed that compromised placental function may alter hormone signaling, including the production of human chorionic gonadotropin and the fetal testosterone surge that masculinizes the external genitalia in early gestation.

The wide confidence intervals on several of these estimates, particularly for multiple gestation and intrahepatic cholestasis, are a reminder of the study’s limitations. With only 96 cases, rare exposures produce imprecise estimates, and the very large odds ratios should be interpreted with caution. The retrospective design also means that only factors recorded in routine clinical records could be examined; unmeasured variables such as paternal factors, specific environmental endocrine disruptors, medication exposures, and detailed dietary patterns were outside the scope of the analysis. The authors are explicit that their findings may help generate hypotheses regarding maternal and fetal characteristics associated with hypospadias and warrant confirmation in larger prospective studies, a appropriately measured conclusion for a single-center dataset.

Nevertheless, the study’s clinical implications are worth taking seriously. Gestational hypertension, intrahepatic cholestasis, and hypothyroidism are all conditions that are routinely screened for or detectable during standard prenatal care, and hypothyroidism in particular is treatable with levothyroxine supplementation. If the association between maternal hypothyroidism and hypospadias is confirmed prospectively, it would raise the tantalizing possibility that a fraction of cases might be preventable through adequate preconception and first-trimester thyroid screening, especially in regions where iodine status and thyroid disease prevalence vary. Similarly, the strong birth weight signal suggests that clinicians caring for growth-restricted fetuses or multiple pregnancies might reasonably include genital examination in newborn assessment, since hypospadias can be missed in the immediate postpartum period.

For now, the Hainan study takes its place in a growing body of evidence that reframes hypospadias not as a mystery of genetics alone but as a developmental outcome shaped by the maternal and fetal environment. The work was funded by the Hainan Provincial Clinical Medical Center and related Hainan provincial science and health funds, and the authors declare no competing interests. As larger prospective cohorts are assembled, the specific odds ratios reported here will be tested and refined, but the study’s central message, that pregnancy complications and fetal growth parameters deserve a central place in hypospadias research, is likely to endure. For families and clinicians alike, that shift in focus from unmodifiable mystery to potentially actionable maternal health is the most consequential finding of all.

Subject of Research: Maternal and fetal risk factors for hypospadias in a Chinese case-control study

Article Title: Maternal and fetal risk factors for hypospadias: a hospital-based case-control study in Southern China

Article References: Bu, W., Li, X., Xuan, Y., Hu, X., & Zhao, Z. (2026). Maternal and fetal risk factors for hypospadias: a hospital-based case-control study in Southern China. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07724-3

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07724-3

Keywords: hypospadias, congenital anomalies, case-control study, maternal health, hypothyroidism, gestational hypertension, intrahepatic cholestasis of pregnancy, birth weight, multiple gestation, pediatric urology, BMC Pediatrics, China

The condition in question is 19p13.3 microdeletion syndrome, a rare and clinically heterogeneous genomic disorder caused by the loss of a small stretch of genetic material near the tip of the short arm of chromosome 19. Because the deleted segment can vary considerably in size from one patient to another, the syndrome does not present as a single recognizable disease. Instead, affected individuals may show global developmental delay, a range of congenital anomalies, and distinct craniofacial differences, with the precise combination and severity of symptoms depending heavily on which genes fall within the deleted region. This genotype-phenotype relationship is a central theme in the literature on the disorder and is precisely what makes each new case report valuable to clinicians trying to map the syndrome’s boundaries.

In the newly reported case, the infant was referred for evaluation of multisystemic complications that had already produced a daunting list of problems. Clinical examination revealed congenital heart defects and severe cardiomegaly, an abnormal enlargement of the heart that in this instance proved fatal. The child also presented with limb anomalies, macrocephaly, or an unusually large head, and recurrent pulmonary infections that compounded the clinical picture. Gastrointestinal manifestations, including vomiting and diarrhea, were a prominent feature of the illness. The authors note that digestive symptoms have rarely been reported in association with this condition, making their patient’s presentation particularly noteworthy for the expanding clinical record.

The diagnostic breakthrough came through a technique known as oligo-array comparative genomic hybridization, or oligo-array CGH. This laboratory method works by comparing a patient’s DNA against a reference genome on a microarray chip populated with thousands of short oligonucleotide probes covering the genome. Differences in fluorescence signal reveal regions where the patient has either lost or gained genetic material, often at a resolution far finer than a standard karyotype can achieve. In this case, the analysis uncovered a deletion measuring 1.8 megabases, a stretch of DNA encompassing 55 genes. Identifying the exact size and gene content of such a deletion is essential, because it allows clinicians to compare the patient against previously reported cases and to begin assigning specific features to specific genes.

Among the 55 genes within the deleted interval, several have already attracted attention in earlier studies of 19p13.3 deletions. The MAP2K2 gene, which encodes the kinase MEK2, a component of the RAS-MAPK signaling pathway that governs cell proliferation and differentiation, has been implicated in cases resembling cardiofaciocutaneous syndrome, a RASopathy characterized by heart defects, distinctive facial features, skin abnormalities, and developmental delay. Previous work has also suggested that PIAS4, a gene involved in sumoylation and the regulation of protein function, may be a major contributor to the proximal 19p13.3 microdeletion phenotype. Other genes in the region have been linked to cardiac development, including members of the ZBTB family of transcription factors, and to brain growth, such as the lamin genes whose variants cause primary microcephaly and the cell-cycle regulator CDH1, whose disruption has been associated with microcephaly, psychomotor retardation, and epilepsy.

The gastrointestinal findings in this case deserve particular emphasis. Although congenital heart disease and neurodevelopmental problems dominate the published literature on 19p13.3 microdeletions, digestive complications have appeared only sporadically. One earlier report described a newborn with a 19p13.3 deletion including MAP2K2 who had cardio-facio-cutaneous syndrome together with gastrointestinal defects, and another described a child with a chromosome 19p13.3 deletion in the context of Peutz-Jeghers syndrome and congenital heart defect. The vomiting and diarrhea observed in the Iranian infant, occurring alongside severe cardiac disease, suggest that the digestive system may be more frequently involved in this syndrome than the sparse literature indicates, and that the gene content of larger deletions may include factors necessary for normal gastrointestinal development or function.

The fatal outcome of the case also highlights the severity that 19p13.3 microdeletions can reach when the deleted segment is large. Severe cardiomegaly in an infant is a grave finding, often reflecting structural heart defects, myocardial dysfunction, or volume overload, and in combination with recurrent pulmonary infections it can create a lethal cycle in which cardiac compromise worsens respiratory disease and vice versa. The authors describe their patient’s phenotype as complex and multisystemic, and the report’s title explicitly characterizes the case as fatal. For clinicians, the message is that infants presenting with combinations of congenital heart defects, unusual head size, limb anomalies, and unexplained gastrointestinal symptoms may warrant genomic investigation even when the initial suspicion does not point to a chromosomal disorder.

The technique used to reach the diagnosis also carries a broader lesson for pediatric medicine. Oligo-array CGH has become a cornerstone of modern cytogenetics precisely because it can detect copy-number variants, deletions, and duplications that are invisible under the microscope. In rare syndromes such as this one, where the phenotype overlaps with many other conditions, genomic analysis is often the only route to a definitive answer. The authors of the report argue that their case underscores the importance of such analysis in understanding the underlying disease mechanisms of the syndrome. Each precisely characterized deletion narrows the search for the genes responsible for individual features, a process already illustrated in the literature by a case that narrowed the subtelomeric 19p13.3 microdeletion region to just 46 kilobases in a patient with cardiac, skeletal, speech, and motor traits.

The accumulated case reports on 19p13.3 deletions now paint a picture of remarkable phenotypic diversity. Published accounts include children with ocular manifestations, ptosis leading to the diagnosis of MAP2K2-linked cardiofaciocutaneous syndrome, lambdoid synostosis in combination with an inherited 16p13.11 microduplication, polyotia, high myopia, learning difficulties, and, in the mirror-image condition of 19p13.3 microduplication, nephrotic syndrome. Recent reports have expanded the spectrum further, describing feeding dysfunction and neurodevelopmental involvement in MAP2K2-related cardiofaciocutaneous syndrome type 4, and retinal development roles for genes such as RAX2. Against this backdrop, the new Iranian case, with its severe cardiomegaly and gastrointestinal manifestations, extends the known boundaries of the syndrome once again and reinforces the principle that deletion size and gene content are the primary determinants of clinical severity.

The research team, led by clinicians at Ali Asghar Children’s Hospital and Iran University of Medical Sciences in Tehran, obtained written informed consent from the parents and received ethics approval from their institution’s ethics committee. The authors declare no competing interests and no external funding for the work. While a single case cannot resolve which of the 55 deleted genes drives which symptom, reports of this kind serve as the raw material for that long-term effort, allowing researchers worldwide to align clinical features with genomic coordinates. For families affected by rare chromosomal disorders, and for the physicians who care for them, each carefully documented case shortens the diagnostic odyssey for the next child and brings the field a step closer to understanding how the loss of a tiny fragment of chromosome 19 can ripple through the development of the heart, the brain, the limbs, and the gut.

Subject of Research: 19p13.3 microdeletion syndrome and its clinical phenotype in a fatal infant case

Article Title: Phenotypic spectrum of 19p13.3 microdeletion: a fatal infant case with severe cardiomegaly and gastrointestinal manifestations

Article References: Eshghi, A., fargi, M. A., Pandi, M., & Tasharrofi, B. (2026). Phenotypic spectrum of 19p13.3 microdeletion: a fatal infant case with severe cardiomegaly and gastrointestinal manifestations. Molecular Biology Reports, 53(1), Article 1633. https://doi.org/10.1007/s11033-026-12791-x

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12791-x

Keywords: 19p13.3 microdeletion, chromosome 19, cardiomegaly, congenital heart defects, gastrointestinal manifestations, oligo-array CGH, MAP2K2, rare genetic disorder, developmental delay, recurrent pulmonary infections, copy-number variant, clinical genetics

The patient first came to medical attention at birth with a striking constellation of findings. He presented with hypotonia, meaning diminished muscle tone, along with bilateral talipes equinovarus, the clubfoot deformity in which both feet are twisted inward and downward. His hands showed adducted thumbs, held drawn in toward the palm, and camptodactyly of the index fingers, a permanent flexion contracture of those fingers. Craniofacial dysmorphic features completed the picture of a multisystem congenital syndrome. Taken together, these findings fall within the spectrum of arthrogryposis-like presentations, in which multiple joints are fixed in abnormal positions from before birth, typically reflecting reduced fetal movement or abnormalities of the neuromuscular system during development.

The clinical course that followed was demanding. The boy experienced delayed motor and speech milestones, meaning he reached the stages of sitting, walking, and speaking significantly later than typically developing children. He developed an abnormal gait and suffered from chronic constipation severe enough to require long-term laxative use, a detail that hints at involvement of the autonomic or enteric nervous system. Over the years he underwent multiple orthopedic and ophthalmologic surgeries to address the structural consequences of his condition, and he continues to receive supportive therapies. Notably, his cognitive development remains preserved, a feature that distinguishes his presentation from many other multisystem developmental syndromes in which intellectual disability is a core component.

The genetic explanation emerged through whole exome sequencing, the technique at the heart of modern rare disease diagnosis. Rather than reading the entire three-billion-letter genome, exome sequencing targets the roughly one to two percent of DNA that encodes proteins, where the majority of known disease-causing variants reside. This approach allows laboratories to scan thousands of genes simultaneously in a single test, and it has transformed the diagnosis of congenital disorders by uncovering variants in genes that no one would have suspected from the clinical picture alone. In this patient, sequencing revealed not one but two different variants in ERBB2, one inherited on each of the two copies of the gene, a configuration known as compound heterozygosity.

The two variants are molecularly distinct in ways that matter for interpreting their effects. The first, designated c.1018C>T, converts a cytosine to a thymine at position 1018 of the coding sequence, changing the codon for arginine at position 340 into a premature stop signal, an alteration annotated as p.Arg340Ter. A premature termination codon of this kind typically triggers nonsense-mediated mRNA decay, a cellular quality-control pathway that destroys transcripts containing early stop signals, or else produces a truncated protein lacking essential functional domains. The second variant, c.3412+1_3412+13del, is a deletion that removes the first nucleotide of intron 3412 together with twelve following intronic nucleotides, destroying the canonical splice donor site at that exon-intron boundary. Splice donor mutations of this type generally cause the splicing machinery to skip the preceding exon or retain intronic sequence, either outcome disrupting the reading frame and abolishing functional protein production. The predicted consequence of this second alteration is annotated as uncertain, denoted p.?, reflecting the difficulty of predicting the exact aberrant transcript.

ERBB2 is far better known to the public under another name: HER2, the growth factor receptor famous as a driver and drug target in certain breast cancers. The gene encodes a receptor tyrosine kinase that sits in the cell membrane and partners with the other three members of the ERBB family, EGFR, ERBB3, and ERBB4. When signaling molecules called neuregulins or other ligands engage these receptors, ERBB2 forms dimers with its partners and switches on intracellular cascades, including the MAP kinase and PI3K-AKT pathways, that tell cells to grow, differentiate, and survive. Unlike its relatives, ERBB2 is a preferred dimerization partner with no known soluble ligand of its own, making it a central hub of the signaling network. In developing tissues, particularly the nervous system and the heart, this signaling is essential, which helps explain why germline variants that cripple the gene can produce effects across multiple organ systems.

Before this report, the clinical literature on ERBB2-related congenital disease rested on a remarkably thin foundation: a single family in which two siblings carried a homozygous missense variant, meaning an identical single-letter protein-altering change on both gene copies. That first description established ERBB2 as a gene implicated in rare multisystem developmental disorders, but a phenotype defined by one family is inherently provisional. The new case changes the picture in two ways at once. First, it adds a second, unrelated family, confirming that ERBB2-associated disease is not confined to a single pedigree. Second, it demonstrates that the disorder can arise from a different genetic mechanism, compound heterozygosity for a nonsense variant and a splice-site deletion, rather than a homozygous missense change, and that the resulting phenotype can include features not observed in the original siblings.

The classification of the variants followed established standards. The report references the criteria jointly published by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, the framework used worldwide to grade sequence variants as pathogenic, likely pathogenic, uncertain, or benign. Under this system, evidence from population frequency databases such as dbSNP, curated mutation collections such as the Human Gene Mutation Database, computational predictions, and the observed segregation of variants within families all feed into the final classification. The authors’ conclusion that this case represents a possible phenotypic extension of the known disorder is deliberately measured: with only a handful of patients described, distinguishing which features are core to the syndrome and which are variable remains an ongoing challenge that each new case helps to resolve.

The diagnostic journey also illustrates why exome sequencing has become the decisive tool for conditions like this one. A presentation combining clubfoot, contractures, hypotonia, and dysmorphic features could plausibly be attributed to dozens of different genes, and for many years such children accumulated diagnoses of unspecified arthrogryposis or syndromic developmental delay. Sequencing collapses that diagnostic odyssey into a single analysis, and in this case it pinpointed a gene whose connection to congenital disease had been established only once before. The Lithuanian team, based at Vilnius University and Vilnius University Hospital Santaros Klinikos, conducted the work with ethics approval from the Vilnius Regional Biomedical Research Ethics Committee and with written informed consent from the patient’s parents for both participation and publication.

For the emerging field of ERBB2-related medicine, the case carries implications in two directions. In oncology, ERBB2 is one of the most intensively targeted genes in human disease, with engineered antibodies and small-molecule inhibitors transforming outcomes for HER2-positive cancers. In genetics, the same gene is now firmly on the map of recessive congenital disorders, and the new report suggests that the clinical spectrum may be wider than the first family implied, potentially including preserved cognition, chronic gastrointestinal involvement, and a pattern of contractures and deformities requiring serial surgical intervention. Every additional patient described sharpens the genotype-phenotype correlations that clinicians will need to counsel families, interpret future sequencing results, and, eventually, evaluate whether therapies aimed at ERBB2 pathways might one day extend from cancer wards to the care of children with rare developmental disease.

Subject of Research: ERBB2-associated multisystem congenital disorder and the expansion of its phenotypic and genetic spectrum through a novel case report

Article Title: Broadening the phenotypic and genetic spectrum of ERBB2-associated multisystem congenital disorder

Article References: Jakubėnaitė, A., Gurskaitė, G., Morkūnienė, A., & Burnyte, B. (2026). Broadening the phenotypic and genetic spectrum of ERBB2-associated multisystem congenital disorder. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07773-8

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07773-8

Keywords: ERBB2, HER2, whole exome sequencing, congenital anomalies, arthrogryposis, compound heterozygosity, rare disease, craniofacial dysmorphic features, receptor tyrosine kinase, hypotonia, genetics, pediatrics

Pulmonary agenesis is among the rarest congenital malformations of the respiratory system. It arises when the lung bud, the embryonic outgrowth of the foregut that normally branches into the airways and lung parenchyma, fails to develop on one side. The result is a complete absence of the affected lung tissue, airway, and vascular supply, rather than an underdeveloped lung that is merely small. The condition can affect either lung, and its reported incidence varies widely across older case series, in part because many affected infants die before a diagnosis is ever made. When one lung is missing, the remaining lung must carry the entire burden of gas exchange, and the cardiovascular system must adapt to a shifted distribution of blood flow. Survival is possible, particularly with unilateral agenesis and no other major anomalies, but the condition is frequently complicated by recurrent infections and, as in this case, pulmonary vascular disease.

The clinical course of the infant described in the report illustrates why the diagnosis is so often delayed. Shortly after birth she developed severe respiratory distress, a presentation that in a neonate is far more commonly explained by pneumonia, sepsis, transient tachypnea, or aspiration than by a missing lung. At the first facility she encountered, clinicians treated her for presumed pneumonia. When she failed to improve, she was referred onward to Tikur Anbessa Specialized Hospital, the tertiary referral center affiliated with Addis Ababa University, where the team led by pediatrician Beniam Tadewos Lamboro took a closer look at what her body was actually doing.

On admission, the physical examination offered the first decisive clues. The baby showed severe intercostal and subcostal retractions, the visible sinking of the chest wall between and beneath the ribs as she struggled to move air. More tellingly, auscultation revealed completely absent air entry on the left side of her chest. A silent hemithorax in a newborn is an alarming finding that demands an immediate explanation, whether that explanation is fluid, collapse, a diaphragmatic hernia, or the absence of lung tissue itself. The examining team recognized that a simple infection could not account for everything they were hearing and seeing.

Chest radiography then sharpened the picture considerably. The X-ray showed opacities in the right middle and lower lobes with air bronchograms, findings consistent with pneumonia, confirming that the infection was real. But it also showed complete opacification of the left hemithorax, together with two features that pointed away from infection and toward a structural problem: crowding of the ribs on the left side and a shift of the mediastinum, the central compartment of the chest containing the heart and great vessels, toward the left. These are classic signs of volume loss. When lung tissue is absent or collapsed, the structures around it fill the void, and the chest wall and mediastinum migrate toward the affected side. In pneumonia, by contrast, the affected side tends to hold its volume or even expand. The combination of infection on one side and volume loss on the other raised the suspicion of a congenital lung anomaly coexisting with pneumonia.

To settle the question, the team performed contrast-enhanced computed tomography of the chest. The CT scan delivered an unambiguous answer: the left main bronchus, the left lung, and the left pulmonary artery were completely absent. There was no vestige of left-sided pulmonary architecture at all. The scan also measured the ratio of the main pulmonary artery diameter to the aortic diameter, which exceeded 1, a radiographic marker associated with elevated pulmonary vascular resistance and pulmonary hypertension. This finding mattered enormously for prognosis and management, because it signaled that the single right lung was not only doing all the oxygenation work but was also facing abnormally high pressures in its circulation.

Echocardiography completed the hemodynamic assessment and revealed the downstream consequences of the missing lung. The right side of the heart, which pumps blood into the pulmonary arteries, was enlarged, a predictable consequence of pumping against increased resistance. The baby had a patent ductus arteriosus, a persistent fetal blood vessel connecting the aorta and the pulmonary artery, measuring 2.5 millimeters with bidirectional shunting, meaning blood was flowing back and forth across it rather than in a single direction. She also had severe tricuspid regurgitation, a leak of the valve between the right atrium and right ventricle, with a peak pressure gradient of 62 millimeters of mercury, a value that indicated severe pulmonary hypertension. In essence, the vascular bed of the lone right lung could not accommodate the entire cardiac output at normal pressures, and the heart was straining against that limitation.

Management proceeded along two parallel tracks. The team supported the infant’s breathing with continuous positive airway pressure, or CPAP, which keeps the airways and air sacs propped open and reduces the work of breathing without requiring invasive ventilation. At the same time, she received medical therapy aimed at lowering pulmonary vascular resistance and supporting cardiac function. This combination reflects the modern understanding of pulmonary agenesis as a cardiopulmonary condition rather than a purely anatomical one: the missing lung is fixed, but the pressures in the pulmonary circulation and the strain on the right heart are potentially modifiable with drugs. Notably, the infant survived the neonatal period, a stage at which many cases of pulmonary agenesis historically proved fatal.

Follow-up over the first nine months of life told a nuanced story. At six months, the child remained dependent on supplemental oxygen but had achieved age-appropriate growth and developmental milestones, an outcome the authors emphasize as meaningful given the severity of her initial presentation. Repeat echocardiography, however, showed that the patent ductus arteriosus had enlarged to 6 to 7 millimeters with persistent bidirectional shunting, indicating that the pulmonary vascular disease had not resolved and may have progressed. By nine months of age she was still on home oxygen and continuing medical therapy, but she had required no further hospitalizations. The report thus documents both the resilience of a child living with a single lung and the chronic, evolving nature of the pulmonary hypertension that accompanies it.

The authors draw a clear practical conclusion from this single case. Congenital lung agenesis can coexist with ordinary respiratory infections, and those infections can mask the underlying anomaly, delaying diagnosis and appropriate counseling. They argue that clinicians in resource-limited settings, where advanced imaging is not always available at first contact, should suspect congenital lung anomalies whenever a neonate or infant presents with persistent respiratory distress accompanied by radiographic signs of volume loss, specifically mediastinal shift and rib crowding on chest radiography. In such circumstances, they recommend considering CT imaging for confirmation. The case is also a broader argument for the value of publishing detailed clinical observations from settings where rare diseases are underreported: every documented case sharpens the pattern recognition of clinicians who may otherwise encounter such a presentation only once in a career, and for the family in this report, that sharpened recognition is what transformed a treatment-resistant pneumonia into a defined, manageable diagnosis.

Subject of Research: A rare case of neonatal left lung agenesis initially misdiagnosed as pneumonia in a resource-limited setting

Article Title: Neonatal left lung agenesis presenting as pneumonia in a resource-limited setting: a case report

Article References: Lamboro, B. T., Girma, S. M., Temesgen, N. E., Mengistu, A. G., & Mamo, Z. B. (2026). Neonatal left lung agenesis presenting as pneumonia in a resource-limited setting: a case report. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07723-4

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07723-4

Keywords: lung agenesis, neonatal respiratory distress, congenital anomalies, pulmonary hypertension, pneumonia, patent ductus arteriosus, chest CT, echocardiography, resource-limited settings, neonatology, case report, BMC Pediatrics