Haemophilia B, severe childhood obesity and other extra-haematological features associated with similar 4Mb-deletions on Xq27: Clinical findings, molecular insights and literature update.

INTRODUCTION: Haemophilia B (HB) is associated with pathogenic variants in F9. Hemizygous deletions encompassing the entire F9 and proximate genes may express extra-haematological clinical phenotypes. AIM: To analyse the genotype/phenotype correlations in two unrelated boys with severe early childhood obesity (SCO), global developmental delay (GDD) and similar bleeding phenotype associated with comparable Xq27 deletions spanning the entire F9 and proximate genes, and characterise the pathogenic events estimating the most likely mutational mechanism involved. METHODS: Entire F9-deletions were detected in three hemizygous unrelated probands with HB: two cases, C#1/C#2, presented SCO and GDD and a control patient (Co), who only had severe bleeding symptoms. Dense SNP-array and case-specific STS walking scan allowed characterisation of the deletion breakpoints. Extensive use of bioinformatics, statistics and clinical databases allowed the investigation of genotype-phenotype associations. RESULTS: Patients C#1/C#2 and Co resulted in a complete F9 and additional gene deletions of variable extensions on Xq26.3-Xq27.2 (C#1/C#2/Co: 4.3Mb/3.9Mb/160Kb). C#1/C#2 common deleted gene SOX3 is directly associated with SCO, GDD and pituitary hypothyroidism (PH) whilst C#2 extra-deleted gene MAGEC2 indirectly relates to anal atresia (AA). Breakpoint analysis revealed the involvement of the mechanisms of Alu/Alu recombination for the first time in HB and non-homologous or alternative end-joining. CONCLUSION: Our results represent the first report of unrelated patients with HB, SCO and GDD. This study and the literature update expand the spectrum of clinical findings and molecular insights observed in patients with HB caused by complete F9 and nearby SOX3 and MAGEC2 gene deletions, which may configure a contiguous gene syndrome.

Prenatal ultrasound manifestations of partial urorectal septum malformation sequence from the first trimester to postnatal: a case report.

BACKGROUND: Urorectal septum malformation sequence (URSMS) is characterized by incomplete partitioning of the genital, rectal, and urinary tracts, resulting in a severe form of anorectal malformation. The partial URSMS, also known as the persistent cloaca, represents a milder variant where a single perineal opening serves as a passage for the urinary, gastrointestinal, and reproductive tracts. CASE PRESENTATION: We present a rare case of partial URSMS accompanied by duplicated vagina and uterus, hydronephrosis, ascites, and anal atresia. CONCLUSIONS: This case report describes the sonographic findings at different stages of pregnancy and their changes throughout gestation.

Outcome after vaginal delivery of women with a previous medical history of surgically corrected anorectal malformations: a systematic review.

OBJECTIVE: Discussion remains on how to advise women with a past medical history of surgically corrected anorectal malformations (ARMs) regarding vaginal delivery. The aim of this review is to evaluate and review the reported obstetrical complications and outcomes after vaginal delivery for these women. DATA SOURCES: A systematic search was performed from inception up to 25 July 2022 in PubMed, Embase.com and Clarivate Analytics/Web of Science Core Collection, with backward citation tracking. STUDY ELIGIBILITY CRITERIA/APPRAISAL: All articles reported on the outcomes of interest in women with a past medical history of surgically corrected anorectal malformation and had a vaginal delivery were included with the exception of editorial comments or invitational commentaries. Screening, data extraction and risk of bias assessment was done by two authors independently with a third and fourth reviewer in case of disagreement. Tool for Quality assessment depended on the type of article. As low quality evidence was expected no meta-analysis was performed. RESULTS: Only five of the 2377 articles screened were eligible for inclusion with a total of 13 attempted vaginal deliveries in eight women. In three patients complications were reported: failed vaginal delivery requiring urgent cesarean section in two patients, and vaginal tearing in one patient. CONCLUSION: High quality evidence regarding outcomes and complications after vaginal delivery in women with a history of surgically corrected anorectal malformation is lacking. Therefore, based upon this systematic review no formal recommendation can be formulated regarding its safety. Future studies are essential to address this problem. TRIAL REGISTRATION: CRD42020201390. Date: 28-07-2020s.

Fetal Sacral Ratio: A Novel Method for Prenatal Sonographic Assessment of Sacral Abnormalities.

OBJECTIVES: The sacral ratio (SR) was described as a postnatal X-ray-based method to detect sacral abnormalities and predict functional prognosis for fecal continence in children with anorectal malformations (ARMs). The present study aimed to describe a novel method of assessing sonographic fetal sacral ratio (f-SR) in a normal population of fetuses. METHODS: Sixty three-dimensional (3D) ultrasound reconstruction images of the sacrum obtained from routine low-risk scans performed between 21 and 26 weeks of gestation served for measurement. The f-SR was calculated in a coronal view as the ratio between lines drawn at the upper and lower levels of the iliac bone and the 5th sacral vertebra. Bland-Altman plots assessed the inter- and intrareader variabilities of measurements. RESULTS: The f-SR in the normal population of fetuses was 0.913 (±0.094). During the study period, three cases with ARM were examined and had a mean f-SR of 0.55. There was good repeatability of measurements and between readers' agreement. CONCLUSIONS: The present study introduces a novel prenatal sonographic f-SR that can be reliably calculated on prenatal 3D ultrasound with good reliability and reproducibility. Future research will identify the clinical significance of f-SR abnormalities in ARM and their long-term impact on continence.

A CLINICAL CASE OF ARTERIAL THROMBOSIS IN A PREMATURE BOY WITH NEONATAL SEPSIS AND HIGH RECTAL ATRESIA.

Occlusion of the venous or arterial vessels in childhood is rather rare but dangerous complication. Occurrence of neonatal thrombosis is 0.5 per 10 000 of live newborns. Promoting factors include congenital defects of coagulation, maternal diabetes, neonatal sepsis, necrotic enterocolitis, asphyxia, and metabolic diseases. More than 90 % cases of neonatal thrombosis are associated with catheterization (umbilical arterial or venous, other central venous lines). Acute arterial thrombosis caused by a peripheral venous catheter is very rare complication, but it can result in severe consequences. The article contains a clinical case of right brachial artery thrombosis in a premature boy with extremely low body weight complicated by development of dry gangrene and amputation of the limb. Complex risk factors promoting development of neonatal arterial thrombosis were found: preterm birth, neonatal sepsis, possible incorrect insertion of a peripheral venous catheter. Associative factors were congenital developmental defects of the intestine (high rectal atresia) and heart (bicuspid aortal valve, open oval foramen), and maternal factors. The authors emphasize their attention on the necessity to continuous education of the medical staff concerning the technique of catheter insertion and care of them, absolute implementation of safety policy concerning nosocomial infection, adequate provision of ultrasound examination devices with high rarefaction sensors, involvement of a multi-disciplinary team of specialists to manage complicated clinical cases.

Anal atresia as the diagnostic clue in VACTERL association: A first-trimester case report.

Anal atresia is the most common malformation occurring in VACTERL association, but it is difficult to diagnose antenatally. We herein present a case of fetal anal atresia in VACTERL association diagnosed by ultrasonography and supported by autopsy. This case emphasizes the clues to ultrasonographic diagnosis of anal atresia at 11-13+6 weeks of gestation, promoting increased awareness of VACTERL association during first-trimester screening.

VACTERL Association with Situs Inversus Totalis: A Unique Combination.

BACKGROUND: VACTERL association is a sporadic, nonrandom series of congenital malformations diagnosed by the presence of three or more of the following: vertebral malformations, anal atresia, cardiac defects, tracheoesophageal fistula, renal malformations, and limb malformations. Situs inversus totalis (SIT) and esophageal malformations are rarely associated. This is the first reported case in North America of VACTERL association with SIT. IMPLICATIONS FOR PRACTICE: Respiratory distress in the term infant requires full exploration of all possible causes because the etiology may be far more complex than routinely diagnosed respiratory distress syndrome. This particular case demonstrates physical exam findings and supportive imaging that would be observed in infants with VACTERL association and with SIT, highlighting considerations when, rarely, both occur simultaneously.

Associated anomalies in cases with anorectal anomalies.

Anorectal anomalies (ARA) are common congenital anomalies. The etiology of ARA is unclear and its pathogenesis is controversial. Cases with ARA often have other non-ARA-associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with ARA were collected in all live births, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 202 cases with ARA, representing a prevalence of 5.21 per 10,000, 100 (49.5%) had associated anomalies. There were 7 (3.3%) cases with chromosomal abnormalities, and 31 (15.3%) nonchromosomal recognized dysmorphic conditions, including 17 cases with Vertebral defects, Anal atresia, Cardiac septal defects, esophageal atresia or TracheoEsophageal fistula, Renal anomalies and radial Limb defects association. Sixty two (30.7%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the urogenital, the musculoskeletal, the cardiovascular, the digestive, and the central nervous systems were the most common other anomalies in the cases with MCA. The anomalies associated with ARA could be classified into a recognizable malformation syndrome or pattern in 38 out of the 100 cases (38%) with associated anomalies. This study included special strengths: each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion, the overall prevalence of associated anomalies, which was close to one in two cases, emphasizes the need for a routine screening for other anomalies in cases with ARA.

Underdiagnosis of Mild Congenital Anorectal Malformations.

OBJECTIVE: To determine whether the frequency and severity of congenital anorectal malformations (CARMs) differs by sex. STUDY DESIGN: We included 129 patients (0-319 weeks old) diagnosed with CARMs, who had been referred to our Department of Pediatric Surgery between 2004 and 2013. Rectoperineal and rectovestibular fistulas were classified as mild CARMs, all others as severe. If a patient was diagnosed with CARM within 48 hours after birth, this was considered an early diagnosis, all others as late. RESULTS: Seventy-five (58%) girls and 54 (42%) boys were diagnosed with different forms of CARM. More patients had mild rather than severe forms of CARM (67% and 33%, respectively, P <.001). We found that 89% of girls had a mild form of CARM, whereas 65% of boys had severe forms (P <.001). All severe forms were diagnosed early, whereas 54% mild forms were diagnosed early and 46% were diagnosed late. CONCLUSIONS: Girls more often have mild forms of CARM, whereas boys more often have severe forms. Overall, the distribution across the sexes is equal. Because chronic constipation can be the only symptom of mild CARMs, it often requires more time to diagnose than severe forms. Many women are, therefore, diagnosed with CARMs at an older age, or they may go undiagnosed altogether. Subsequently, these women have a greater risk of full rupture during vaginal delivery.

Previous miscarriages and GLI2 are associated with anorectal malformations in offspring.

STUDY QUESTION: Are anorectal malformations (ARMs) associated with previous miscarriages or single nucleotide polymorphisms (SNPs) in the Bone Morphogenetic Protein 4 (BMP4) and GLI family zinc finger 2 (GLI2) genes? SUMMARY ANSWER: The SNP rs3738880 in GLI2 and miscarriages were associated with ARM, especially in patients with multiple congenital anomalies (MCA). WHAT IS KNOWN ALREADY: ARM are one of the most common birth defects of the gastrointestinal tract. The etiology is likely to be multifactorial, involving both environmental and genetic factors. SNPs in BMP4 and GLI2 genes were associated with ARM in non-Caucasian populations. During a patient information day, several mothers of ARM patients reported their concerns about previous miscarriages. STUDY DESIGN, SIZE, DURATION: A case-control study was performed among 427 ARM patients and 663 population-based controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined the associations of ARM with SNPs in GLI2 and BMP4 using DNA samples of the children and associations with previous miscarriages using parental questionnaires. In addition, gene-gene and gene-environment interaction analyses were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The SNP rs3738880 in GLI2 was associated with ARM, especially in patients with MCA (homozygous GG-genotype: odds ratio (OR): 2.1; 95% CI: 1.2, 3.7). We identified previous miscarriages as a new risk factor for ARM, especially when occurring in the pregnancy directly preceding the index pregnancy and in patients with MCA (OR: 2.1; 95% CI: 1.3, 3.5). No association with rs17563 in BMP4, nor gene-gene or gene-environment interactions were found. LIMITATIONS, REASONS FOR CAUTION: The possibility of recall errors for previous miscarriage, but we expect these errors to be limited, as a miscarriage is a major life event. In addition, potential misclassification regarding miscarriages and stillbirth, but sensitivity analyses showed that this did not influence our results. WIDER IMPLICATIONS OF THE FINDINGS: This study showed associations of ARM with rs3738880 in GLI2 and with previous miscarriages. Both associations were stronger in patients with MCA, showing the importance of stratifying the analyses by patients with isolated ARM or MCA. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Radboudumc. The authors have no conflict of interest to disclose.

Temporary occipital fixation in young children with severe cervical-thoracic spinal deformity.

OBJECTIVE The long-term effects of instrumentation and fusion of the occipital-cervical-thoracic spine on spinal growth in young children are poorly understood. To mitigate the effects of this surgery on the growing pediatric spine, the authors report a novel technique used in 4 children with severe cervical-thoracic instability. These patients underwent instrumentation from the occiput to the upper thoracic region for stabilization, but without bone graft at the craniovertebral junction (CVJ). Subsequent surgery was then performed to remove the occipital instrumentation, thereby allowing further growth and increased motion across the CVJ. METHODS Three very young children (15, 30, and 30 months old) underwent occipital to thoracic posterior segmental instrumentation due to cervical or upper thoracic dislocation, progressive kyphosis, and myelopathy. The fourth child (10 years old) underwent similar instrumentation for progressive cervical-thoracic scoliosis. Bone graft was placed at and distal to C-2 only. After follow-up CT scans demonstrated posterior arthrodesis without unintended fusion from the occiput to C-2, 3 patients underwent removal of the occipital instrumentation. RESULTS Follow-up cervical spine flexion/extension radiographs demonstrated partial restoration of motion at the CVJ. One patient has not had the occipital instrumentation removed yet, because only 4 months have elapsed since her operation. CONCLUSIONS Temporary fixation to the occiput provides increased biomechanical stability for spinal stabilization in young children, without permanently eliminating motion and growth at the CVJ. This technique can be considered in children who require longer instrumentation constructs for temporary stabilization, but who only need fusion in more limited areas where spinal instability exists.

Transient Distention of Right Posterior Located Sigma, a New Sonographic Sign for the Prenatal Diagnosis of Anal Atresia.

We describe a new sonographic sign for the detection of anal atresia in the early midtrimester on transvaginal sonography. In six cases of fetal anal atresia, the finding of a transient, distended, and right-sided sigmoid colon was observed at 13-16 weeks' gestation. Three cases have undergone pregnancy termination due to multiple anomalies. In the other three, the colonic distension resolved by 19 weeks' gestation. In two of these, the finding was isolated, and no other anomalies were detected. In all six cases, anal atresia or cloaca was confirmed on postabortal autopsy or after delivery. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:160-162, 2017.

Prenatal Diagnosis of Anal Atresia - A Case Report.

Anal atresia can be divided into high type and low type depending on the relationship between the distal rectal pouch and the puborectalis muscle. Prenatal diagnosis of anal atresia is very challenging. Indirect findings include dilated distal bowel segments and calcified intraluminal meconium in 2nd & 3rd trimester. Direct findings include no PAMC (perianal muscular complex) and no target sign (hypoechoic anal sphincter and echogenic anal mucosa). PAMC is intact in low atresia, no PAMC can only be applied to high atresia. A visible echogenic anal mucosa excludes all cases of high atresia and most cases of low atresia, with the exception of the mildest cases with only a thin membrane covering the anal opening.

Congenital Anorectal Malformation Severity Does Not Predict Severity of Congenital Heart Defects.

OBJECTIVE: To determine the prevalence of congenital heart defects (CHDs) in patients with mild or severe congenital anorectal malformations (CARMs), and whether all patients with CARM need pediatric cardiology screening. STUDY DESIGN: We included 129 patients with CARM born between 2004 and 2013, and referred to University Medical Center Groningen. Recto-perineal and recto-vestibular fistulas were classified as mild CARMs, all others as severe. Significant patent foramen ovale, secundum atrial septal defect, and small ventricular septum defect were classified as minor CHDs, all others as major. RESULTS: Of 129 patients with CARM, 67% had mild CARM, 33% severe CARM, and 17% were additionally diagnosed with CHD. CHDs were distributed equally in patients with mild or severe CARMs. Patients with multiple congenital abnormalities were more frequently diagnosed with CHD (n = 16, 36%) than patients without multiple congenital malformations (n = 5, 9%, P = .001). Patients with CARM diagnosed with CHD using pediatric cardiac echo screening were younger than 3 months of age at diagnosis. Earlier general pediatric examinations missed 7 (50%) children with mild and 4 (50%) with severe CHDs. CONCLUSIONS: The severity of CARM could predict neither prevalence nor severity of CHD. More than one-half of CHDs were missed during the first physical examination. No new CHDs were found in patients older than 3 months of age at the time CARMs were diagnosed. We recommend screening all patients with CARM younger than 3 months of age for CHD at the time CARM is diagnosed. Preoperative echocardiography should be the rule in children younger than 3 months of age and with multiple congenital anomalies.

Low vertebral ano-rectal cardiac tracheo-esophageal renal limb screening rates in children with anorectal malformations.

BACKGROUND: The aim of this study was to establish the rate of screening for associated cardiac, vertebral, spinal cord, urologic, and limb anomalies vertebral ano-rectal cardiac tracheo-esophageal renal limb (VACTERL) in children with anorectal malformation (ARM). METHODS: We performed a retrospective cohort study using the Medicaid Analytic eXtract database which contains enrollment and utilization claims and demographic information from all Medicaid enrollees. Patients born between January 2005 and December 2008 with International Classification of Diseases, Ninth Revision codes for a diagnosis of ARM within 30 days of life, an ARM procedure code during the first year of life, and a minimum of 12 months of continuous enrollment were included. VACTERL screening was determined using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes for diagnostic tests used to detect these anomalies. RESULTS: A total of 406 patients were identified (231 males). Evaluation of the spinal vertebrae was performed in 94% of patients (381 of 406). Spinal cord evaluation was performed in 57% (231 of 406): 52% (121 of 231) received spinal ultrasound (US), 24% (56 of 231) received spinal magnetic resonance imaging, and 23% (54 of 231) received both. Sacral radiographs were performed in 8% (32 of 406) and 77% (313 of 406) underwent an echocardiogram. Genitourinary evaluation was performed in 84% (341 of 406): 67% (229 of 341) received renal US, 8% (27 of 341) received abdominal US, and 25% (85 of 341) received both. Limb evaluation was recorded in 19% (76 of 406). Multiple screening including an echocardiogram, spinal radiograph, spinal cord evaluation, and renal evaluation was performed in 45% (181 of 406); 2% (7 of 406) did not receive any screening tests. CONCLUSIONS: Low VACTERL screening in children with ARM suggests that associated anomalies may be undiagnosed which may lead to increased long-term morbidity.

Sonographic Determination of Type in a Fetal Imperforate Anus.

OBJECTIVES: The purpose of this study was to determine the type of an imperforate anus by using sonography in the prenatal period. METHODS: This retrospective study evaluated the fetal anus in all pregnant women, including low- and high-risk populations, between February 2010 and November 2013. High-type imperforate anuses were diagnosed by prenatal sonography when the anal sphincter muscles and anal canal mucosa were not visible. Low-type imperforate anuses were prenatally suspected when at least 1 of the following was present: (1) a small anus; (2) no visible anal mucosa; or (3) close location of the genitalia by the anus without a visible perineal body, particularly in a female fetus. RESULTS: Among the 9499 fetuses, 41 were prenatally suspected of having an imperforate anus, and 32 were confirmed to have this disorder. During the same study period, there were 11 false-negative cases, for a diagnostic sensitivity rate of 74%. All 9 fetuses who were confirmed to have a normal anus were prenatally suspected of having a low-type imperforate anus. Among the 32 fetuses with a confirmed imperforate anus, 19 were confirmed to have a high or intermediate type and 13 to have a low type. The type in 3 fetuses was incorrectly determined prenatally. CONCLUSIONS: Although an imperforate anus is not always diagnosed prenatally, its type can be determined by prenatal sonography.

Genetic and nongenetic etiology of nonsyndromic anorectal malformations: a systematic review.

Congenital anorectal malformations (ARMs) are one of the most frequently observed birth defects of the digestive system. However, their etiology remains elusive. Therefore, we aim to summarize and critically appraise all existing literature on the genetic and nongenetic etiology of nonsyndromic ARM and to conclude with unifying hypotheses and directions for future research. A structured literature search on English language human studies was conducted in PubMed and Embase up to October 1, 2013, resulting in 112 included articles. Research on the identification of genes underlying nonsyndromic ARM is remarkably scarce. Most studies were focused on screening of candidate genes for mutations or single-nucleotide polymorphisms, which did not yield any substantial evidence. Nongenetic factors fairly consistently found to be associated with ARM are assisted reproductive techniques, multiple pregnancy, preterm delivery, low birth weight, maternal overweight or obesity, and preexisting diabetes. This review provides indications for the involvement of both genes and nongenetic risk factors in the etiology of ARM. In future studies, large cohorts of patients with ARM from national and international collaborations are needed to acquire new hypotheses and knowledge through hypothesis-generating approaches. Challenges for future studies may also lie in the investigation of gene-gene and gene-environment interactions.

Blepharo-cheilo-dontic (BCD) syndrome: expanding the phenotype, case report and review of literature.

The combination of lagophthalmia, euryblepharon, ectropion of lower eyelids, distichiasis, bilateral cleft lip and palate, and oligodontia comprises the blepharo-cheilo-dontic (BCD) syndrome. This combination has been found sporadically or with positive family history and inherited as an autosomal dominant condition with variable expression. We described a Saudi boy with the cardinal signs consistent with the BCD syndrome. In addition to the common components of BCD syndrome that involve eyelids, lip, and teeth abnormalities, this patient is the third reported BCD case with imperforate anus, the second with thyroid agenesis, and the first with lumbosacral meningomyelocele.

No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations.

BACKGROUND: Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM. METHODS: A case-control study was conducted among 371 nonsyndromic ARM cases and 714 population-based controls born between 1990 and 2012 using maternal questionnaires and DNA samples from mother and child. Cases were treated for ARM at departments of Pediatric Surgery of the Radboud university medical center, Sophia Children's Hospital-Erasmus MC Rotterdam, and the University Medical Center Groningen in The Netherlands and hospitals throughout Germany. RESULTS: No association with folic acid use was present (odds ratio = 1.1; 95% confidence interval: 0.8-1.4) for ARM as a group. Infant and maternal MTHFR C677T polymorphisms were weakly associated with isolated ARM in particular. Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFR C677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM. The relative excess risks due to interaction did not clearly indicate interaction on an additive scale either. CONCLUSION: This first study investigating interactions between periconceptional folic acid supplement use and infant and maternal MTHFR C677T polymorphisms in the etiology of ARM did not provide evidence for a role of this gene-environment interaction.

Spondylocostal Dysostosis with Anal Atresia and Urogenital Anomalies in a Young Infant: First Case Entity of Casamassima-Morton-Nance Syndrome from Asia.

Casamassima-Morton-Nance syndrome (CMNS) includes a heterogeneous group of spondylocostal dysostosis along with anal atresia and genitourinary abnormalities. In 1981, Casamassima et al first described the syndrome in a fetus, and since then, only seven such cases have been reported so far. CMNS phenotype shows a significant clinical variability as documented in the reported cases. Etiology remains unknown yet, and it carries a poor prognosis. Here, we reported on a young female infant born out of nonconsanguineous marriage with normal karyotype and spondylocostal dysostosis, anal and genitourinary malformations suggesting CMNS. Ours is the eighth, and first case entity of CMNS reported from Asia as per the literature search. In our case, the additional feature of bilateral clubfoot has not been documented earlier in the literature. It extends the clinical spectrum of the syndrome and prompts us to consider it a close differential diagnosis to VACTERL (vertebral defects, anal atresia, cardiac malformations, tracheoesophageal fistula/esophageal atresia, renal anomalies, limb abnormalities) syndrome, which is commonly known and diagnosed. It also raises the question of whether cases of CMNS are being misdiagnosed as VACTERL syndrome due to its rarity.