Initially suspected case of prenatal VACTERL association ultimately diagnosed as Currarino syndrome via magnetic resonance imaging: a case description

Introduction

The prenatal differentiation between Currarino syndrome (CS) and VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, esophageal atresia, renal anomalies, and limb abnormalities) represents a significant diagnostic challenge with profound clinical implications. Despite both entities sharing overlapping features such as vertebral and anal anomalies, the presence of a presacral mass is pathognomonic for CS (1,2). However, the exact prevalence of CS is difficult to determine due to its phenotypic variability. The estimated global prevalence ranges between 1 and 9 per 100,000 individuals (3). Ultrasonography, as the primary screening tool for CS, may occasionally fail to detect this mass, particularly when its echogenicity mimics adjacent bowel loops. Although specific quantitative data on ultrasound’s diagnostic sensitivity and specificity for CS are lacking in the literature, it remains a crucial initial screening modality (4,5). This diagnostic uncertainty underscores the critical role of complementary fetal magnetic resonance imaging (MRI). Fetal MRI is widely regarded as the definitive imaging modality for prenatal evaluation in such complex cases. Its superior soft-tissue contrast resolution, multiplanar capability, and large field of view can confirm the presence and nature of a presacral mass with high confidence, accurately delineate complex vertebral anomalies, and critically assess the associated spinal cord abnormalities, most notably tethered cord. These capabilities are often unmatched by ultrasound. Therefore, despite the lack of formally quantified accuracy metrics, fetal MRI serves as the cornerstone and best available tool for definitive diagnosis and differential diagnosis, directly guiding subsequent management (5-8). Achieving a precise prenatal diagnosis is not merely an academic exercise: it is essential for accurate genetic counseling, prognostication, and the formulation of a targeted multidisciplinary management plan, thereby directly influencing parental decision-making and perinatal care pathways.

Case presentation

A 32-year-old woman (gravida 2 and para 1) conceived via in vitro fertilization (IVF). She had a history of hypothyroidism and anticardiolipin syndrome, with thyroid function being well controlled both before embryo transfer and throughout the pregnancy (see Table S1 for detailed serial thyroid function tests). First-trimester ultrasound revealed an increased nuchal translucency of 3.3 mm. A detailed ultrasound scan (Figure 1A-1C) at 25 weeks of gestation identified a constellation of findings including sacrococcygeal hypoplasia, anorectal agenesis, butterfly vertebrae, left renal hypoplasia with hydronephrosis, ambiguous external genitalia, gallbladder agenesis, a single umbilical artery, and a persistent left superior vena cava. The multisystem involvement from the initial prenatal findings suggested VACTERL association. A definitive presacral mass was not confidently identified on ultrasound, as its echoes were difficult to distinguish from the surrounding bowel. To further characterize the complex anatomy, fetal MRI was subsequently performed. The MRI (Figure 1D-1F) clearly identified a well-defined presacral mass, separate from the rectal pouch and spinal canal, and further confirmed all other sonographic findings. This critical observation redirected the diagnosis to CS. Chromosomal microarray analysis yielded a normal result, and trio-based whole-exome sequencing did not reveal any pathogenic variants, including within the motor neuron and pancreatic homeobox 1 gene (MNX1). Following multidisciplinary counseling, the pregnancy was terminated at 27 weeks. Postmortem examination (Figure 1G) and histopathological analysis (Figure 1H-1J) confirmed all prenatal findings and definitively diagnosed the presacral mass as a mature cystic teratoma. All procedures described in this article were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Pre- and postnatal images of Currarino syndrome. (A) Sacrococcygeal bone defect below the S2 vertebra (arrow) revealed by ultrasound. (B) Ambiguous external genitalia (arrow) revealed by ultrasound. (C) Presacral mass (*) retrospectively identified on ultrasound after MRI diagnosis. (D) External genital abnormalities (arrow) and a presacral mass (*) on MRI (T2-weighted sagittal view). (E) Butterfly vertebrae (arrow) on MRI (T2-weighted coronal view). (F) Hypoplasia of the left kidney with hydronephrosis and a cyst (arrow) on MRI (T2-weighted coronal view). (G) Butterfly vertebrae and sacrococcygeal bone defect (arrow) confirmed by postmortem X-ray. (H) Sacrococcygeal hypoplasia, lumbar widening, and vertebral fusion confirmed by autopsy (arrow). (I) Imperforate anus (arrow). (J) Abnormal external genitalia (arrow). MRI, magnetic resonance imaging.

Discussion

This case vividly illustrates a common diagnostic pitfall in prenatal imaging—the sonographic masking of a presacral mass—and demonstrates how fetal MRI can decisively resolve such ambiguity. The initial diagnosis of VACTERL association was logical given the broad spectrum of observed anomalies; however, the subsequent MRI identification of the characteristic presacral mass was pivotal in establishing the correct diagnosis of CS (2,9). This distinction carries substantial clinical weight. From a genetic counseling perspective, while this specific case was sporadic and MNX1 [formerly known as human lymphocyte homeobox 9 (HLXB9)]-negative, CS can follow an autosomal dominant inheritance pattern in familial cases, conferring a significantly higher recurrence risk as compared to the typically sporadic VACTERL association. Pathogenic mutations in this gene are identified in nearly all familial cases and approximately 30% of sporadic cases (3,6,10). This information is fundamental for families considering future pregnancies.

Accurate differentiation between CS and VACTERL also critically informs prognosis and underscores the importance of timely intervention. Regarding the specific risks associated with CS, while an overall population-based mortality rate is not well established, the literature highlights significant mortality risks associated with life-threatening complications. These include severe infections, such as recurrent meningitis from fistulous tracts (with the reported mortality being as high as 56%), and the potential for malignant transformation of presacral teratomas (11,12). Furthermore, the precise diagnosis critically informs prognosis and postnatal management strategy. A diagnosis of CS specifically alerts the clinical team to the presence of the presacral mass, which may necessitate neurosurgical evaluation for potential cord tethering and requires a different initial surgical focus (e.g., addressing of the anorectal malformation and potential resection of the mass), which contrasts with the more varied and system-specific interventions required for VACTERL (e.g., for tracheoesophageal fistula or cardiac defects). For families deciding upon whether to continue the pregnancy, a definitive diagnosis allows for more accurate and detailed counseling regarding the likely sequence of interventions, long-term functional outcomes, and quality-of-life projections. This clarity is therefore essential for supporting truly informed decision-making and parental autonomy.

The conception of this patient via IVF raises the question of a potential link to CS. Isolated case reports, including a prior description of CS following IVF, exist in the literature (12). Furthermore, a large case–control study demonstrated that assisted reproductive techniques (ARTs), including IVF, significantly increase the risk for anorectal malformations—a defining component of CS (13). Our case constitutes further clinical evidence for this possible association, and continued attention and further investigation are warranted to clarify the potential role of ART as a risk factor for CS.

Consequently, in cases of suspected caudal regression or VACTERL spectrum with sacral/anal involvement, proceeding to fetal MRI for dedicated evaluation of the presacral space is not only beneficial but often necessary. It ensures diagnostic accuracy, which in turn, forms the indispensable foundation for appropriate counseling, tailored multidisciplinary planning, and optimized perinatal management, regardless of the ultimate pregnancy outcome.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2639/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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