Moderate altitude as a risk factor for isolated congenital malformations. Results from a case-control multicenter-multiregional study.

BACKGROUND: Living in high-altitude regions has been associated with a higher prevalence of some birth defects. Moderate altitudes (1500-2500 m) have been associated with some congenital heart diseases and low birth weight. However, no studies have been conducted for other isolated congenital malformations. OBJECTIVES: To estimate the prevalence at birth of isolated congenital malformations in low and moderate altitudes and to determine if moderate altitudes are a risk factor, such as high altitudes, for isolated congenital malformations adjusted for other factors. METHODS: The study consisted of a case-control multicenter-multiregional study of 13 isolated congenital malformations. Cases included live births with isolated congenital malformations and controls at low (10-1433 m) and moderate altitudes (1511-2426 m) from a Mexican registry from January 1978 to December 2019. Prevalence per 10,000 (95% CI) per altitude group was estimated. We performed unadjusted and adjusted logistic regression models (adjusted for maternal age, parity, malformed relatives, socioeconomic level, and maternal diabetes) for each isolated congenital malformation. RESULTS: Hydrocephaly and microtia had a higher at-birth prevalence, and spina bifida, preauricular tag, and gastroschisis showed a lower at-birth prevalence in moderate altitudes. Moderate altitudes were a risk factor for hydrocephaly (aOR 1.39), microtia (aOR 1.60), cleft-lip-palate (aOR 1.27), and polydactyly (aOR 1.32) and a protective effect for spina bifida (aOR 0.87) compared with low altitudes. CONCLUSIONS: Our findings provide evidence that moderate altitudes as higher altitudes are an associated risk or protective factor to some isolated congenital malformations, suggesting a possible gradient effect.

The downregulation of genes encoding muscle proteins have a potential role in the development of scrotal hernia in pigs.

BACKGROUND: Testicular descent is a physiological process regulated by many factors. Eventually, disturbances in the embryological/fetal development path facilitate the occurrence of scrotal hernia, a congenital malformation characterized by the presence of intestinal portions within the scrotal sac due to the abnormal expansion of the inguinal ring. In pigs, some genes have been related to this anomaly, but the genetic mechanisms involved remain unclear. This study aimed to investigate the expression profile of a set of genes potentially involved with the manifestation of scrotal hernia in the inguinal ring tissue. METHODS AND RESULTS: Tissue samples from the inguinal ring/canal of normal and scrotal hernia-affected male pigs with approximately 30 days of age were used. Relative expression analysis was performed using qPCR to confirm the expression profile of 17 candidate genes previously identified in an RNA-Seq study. Among them, the Myosin heavy chain 1 (MYH1), Desmin (DES), and Troponin 1 (TNNI1) genes were differentially expressed between groups and had reduced levels of expression in the affected animals. These genes encode proteins involved in the formation of muscle tissue, which seems to be important for increasing the resistance of the inguinal ring to the abdominal pressure, which is essential to avoid the occurrence of scrotal hernia. CONCLUSIONS: The downregulation of muscular candidate genes in the inguinal tissue clarifies the genetic mechanisms involved with this anomaly in its primary site, providing useful information for developing strategies to control this malformation in pigs and other mammals.

Surgical Management of Bilateral Single-System Ectopic Ureters (BSSEUs) in a Pediatric Patient: A Report of a Rare Case and Literature Review.

Bilateral single-system ectopic ureters (BSSEUs) are among the rarest entities encountered in pediatric urology. A BSSEU occurs when the ureteric buds originate cranially from the mesonephric ducts, causing a delay in their integration into the urogenital sinus. It presents as continuous incontinence in females, whereas symptoms like infection and discomfort are present in males. We describe a case involving a BSSEU opening into the vagina and urethra, with the patient experiencing continuous urinary incontinence, and its diagnosis and management. Here, We discuss a rare case of a four-year-old girl exhibiting continuous urinary incontinence or dribbling associated with recurrent urinary tract infections (UTIs) attributed to bilateral ectopic ureters. Imaging modalities, including contrast-enhanced computed tomography(CECT) and MRI, revealed the presence of BSSEUs accompanied by hydroureteronephrosis. The condition was managed with prompt surgical intervention involving bilateral ureteric reimplantation. Subsequent to the procedure, the patient experienced a significant improvement in continence mechanism and bladder capacity, obviating the requirement of urinary diversion procedure appendicovesicostomy or bladder neck reconstruction. Notably, while BSSEUs are an uncommon presentation, their timely and appropriate management is paramount in preventing potential renal damage. This case underscores the significance of vigilant monitoring and proactive intervention in addressing such complex urological anomalies in pediatric patients.

Congenital malformation in green turtle embryos and hatchlings.

Successful embryonic development depends on the interaction between genetic factors and environmental variables. Congenital malformations in sea turtles can result from extreme conditions during the incubation period, reducing hatching success and potentially impeding population recovery. We aimed to characterize the congenital malformations found in green turtle nests, determine their prevalence and severity, and understand their drivers during the 2022 nesting season on Samandag beach on northern Mediterranean nesting beaches. A total of 2986 examples of congenital malformations were observed in 362 out of 907 green turtle nests. The prevalence of congenital malformations per nest was 39%, and the severity (the number of malformed individuals per nest) was 3.8%. Nests with congenital malformations exhibited a lower mean distance from the sea, a shorter incubation duration (a proxy for incubation temperature), lower hatching success, a larger clutch size, and higher mortality at late embryonic and hatchling stages than nests without congenital malformations. There was no significant difference in total mortality between these two nest types. A total of 52 different congenital malformations were recorded, 2 of which were observed for the first time in sea turtles and 28 for the first time in green turtles. The results suggest that congenital malformations may be related to nest temperature and clutch size, while overall mortality may be independent of malformations. Pigmentation disorders and craniofacial malformations typically coexist in cases of multiple malformations. Long-term monitoring of congenital malformations is crucial, as it can provide clues about the health status of the nesting beach and nesting colony.

Pediatric Limb Asymmetry: A Unique Presentation of Angioosteohypertrophic Syndrome.

Parks-Weber syndrome (PWS), also known as Klippel-Trenaunay-Weber syndrome, is a rare congenital bone vascular syndrome first described in 1900. It is characterized by arteriovenous malformations in a limb, leading to disproportionate limb growth and potential heart failure. Unlike Klippel-Trenaunay syndrome, PWS manifests arteriovenous malformations with abnormal connections between the arteries and veins of the affected limb. The management of this syndrome, similar to that of Klippel-Trenaunay syndrome, relies mainly on symptomatic treatment. We report the first case of angioosteohypertrophic syndrome diagnosed at CHU Med VI Oujda, in a patient aged seven years and eight months. This syndrome manifested primarily in the right upper limb, characterized by asymmetry in both upper limbs, thermal disparity, a cutaneous nevus, and venous ectasia in the right arm. The diagnosis was further substantiated through arteriography, confirming the presence of an arteriovenous fistula.

Ectopic right coronary artery arising from the pulmonary artery: a rare congenital malformation.

An ectopic origin of the right coronary artery from the pulmonary artery is an extremely rare congenital malformation. This case report aimed to review our experience in the diagnosis and treatment of coronary artery anomalies. We report a case of ectopic origin of the right coronary artery from the pulmonary artery. We analyzed the taxonomy and clinical implications of the ectopic origin of the coronary artery. The findings of this case may increase patients' and clinicians' awareness of this anomaly.

Thoracolumbar myelocele repair: how I do it.

BACKGROUND: Myelocele is a rare form of open spina bifida. Surgical repair is recommended prenatally or in the first 48 h. In some cases, the repair may be delayed, and specific surgical factors need to be considered. METHOD: We give a brief overview of the surgical anatomy, followed by a description of the surgical repair of a thoracolumbar Myelocele in an 11-month-old child. CONCLUSION: Surgical repair of the Myelocele stabilizes the neurological status, prevents local and central nervous system infections. The understanding of Myelocele anatomy enables its removal while preserving as much healthy tissue as possible and restoring normal anatomy.

Ectopic Ureter Opening in Vagina: A Rare Cause of Nonfunctional Kidney and Urinary Incontinence in a Pediatric Patient.

An ectopic ureter is a condition characterized by a ureter, whether single or duplex, that fails to open in the trigone area of the urinary bladder but instead drains outside of it. This anomaly arises congenitally due to abnormal migration of the ureteric bud during its insertion into the urinary bladder. Here, we present a case involving an ectopic ureter draining into the vagina, with continuous urinary incontinence. We discuss the diagnosis, evaluation, and management of urinary incontinence in a female because of an ectopic ureter. A 9-year-old girl child presented with a continuous urinary leak or incontinence requiring the use of one to two pads per day that progressively became wetter throughout the day. Physical examination revealed a normal urethral meatus and vagina without obvious visible dribbling of urine at the introitus. CT urography showed significant dilation of the right ureter, causing hydroureter and ectopic insertion of the tortuous right ureter near the external urethral orifice at the vaginal vestibule, along with an atrophic right kidney. A DTPA (diethylenetriamine pentaacetate) scan indicated the nonfunctional status of the right kidney. The patient underwent a right nephroureterectomy, leading to a complete resolution of urinary incontinence. Ectopic ureter causing nonfunctional kidney and urinary leak or incontinence is rare. This case emphasizes the importance of a comprehensive diagnostic workup for achieving a better prognosis and initiating early treatment of ectopic ureter.

Liver Transplantation as a Treatment for Unresectable Hepatic Adenoma in a Patient With Abernethy Syndrome.

Abernethy syndrome is a rare congenital anomaly characterized by an intrahepatic or extrahepatic portosystemic shunt. Most patients are asymptomatic; however, due to the alteration in, or lack of, a portovenous flow, patients with Abernethy syndrome are at high risk of developing sequelae of liver failure. Once these complications develop, the only definitive treatment is transplantation. Patients with Abernethy syndrome are also at a higher risk of developing benign and malignant liver lesions, including hepatic adenomas. Here, we describe the first case of deceased donor liver transplantation as a treatment for a patient with type 1 Abernethy syndrome complicated by large, unresectable hepatic adenoma, found to have focal hepatocellular carcinoma on pathologic examination. Our male patient was found to have elevated liver enzymes at age 33, during a routine outpatient medical appointment. Despite being asymptomatic, his history of prior liver resection prompted CT imaging, which revealed two large liver lesions concerning for hepatic adenomas. When surveillance imaging showed a significant growth of the liver lesions, biopsy was pursued, which confirmed a diagnosis of hepatic adenomas. However, given the size of these lesions, resection was not a viable option for the patient. Instead, the patient underwent liver transplantation at age 41, which he tolerated well. Our case demonstrates the utility of deceased donor liver transplantation as a treatment for patients with Abernethy syndrome complicated by unresectable adenomas.

Clinical and Imaging Characteristics of Herlyn-Werner-Wunderlich Syndrome: a Comprehensive Analysis.

PURPOSE: To describe the clinical and imaging characteristics of Herlyn-Werner-Wunderlich syndrome (HWWS). METHODS: This study presented an observational case series involving consecutive patients diagnosed with HWWS, whose medical records were retrospectively reviewed. From June 2012 to December 2022, there were a total of 85 patients with HWWS enrolled in our study. We obtained the medical history, including demographic characteristics, clinical presentation, treatment, complications, and radiologic examinations performed. Patients > 18 years of age (n = 58) were recontacted. RESULT: In our analysis, 27 patients were categorised as having complete obstruction, and 58 were categorised as having incomplete obstruction. The mean age at the onset of symptoms and diagnosis of complete obstruction was significantly younger than incomplete obstruction (P < 0.05). For complete obstruction, the median time between menarche and the onset of symptoms was 2.1 years, while for incomplete obstruction, it was 5.3 years. There was a significantly lower incidence of intermittent mucopurulent discharge, irregular vaginal haemorrhage, and occasional examination findings of complete obstruction than incomplete obstruction (P < 0.05). Complete obstruction was significantly associated with dysmenorrhea and pelvic endometriosis compared with incomplete obstruction (P < 0.05). CONCLUSIONS: There are distinct clinical differences between patients with complete obstruction of the hemivagina and those with incomplete obstruction. HWWS can manifest as various combinations of uterine anomalies, communications anomalies, and renal anomalies. Early recognition and treatment can avoid complications and preserve fertility. KEYSWORDS: Herlyn-Werner-Wunderlich syndrome (HWWS); complete obstruction; incomplete obstruction; obstructed hemivagina; congenital malformation.

Prenatal detection and management challenges of a huge cystic hygroma of the neck in a resource-constraint setting: A case report.

INTRODUCTION AND IMPORTANCE: Cystic hygroma is a benign congenital malformation of lymphatic and blood vessels, with an incidence of 1 in 6000 live births. Most cases are associated with genetic syndromes and can compromise fetal viability. Due to its rarity, comprehensive data is limited, mainly relying on case reports. CASE PRESENTATION: A 21-year-old pregnant woman at 27 weeks' gestation presented to triage with abdominal pain. Abdominal ultrasound revealed a single living female fetus with an estimated fetal weight of 734 g and a complex cystic mass causing hyper-extension of the neck. The pregnancy was terminated given the poor prognosis. Histopathology of the mass confirmed it to be a cystic hygroma. CLINICAL DISCUSSION: In limited-resource settings, management of huge cystic hygromas often necessitates termination of pregnancy due to a lack of sufficient resources for complex interdisciplinary interventions for the mother and infant after birth. In such cases, focus should be shifted toward promoting shared decision-making and sensitive patient counseling. CONCLUSION: Cystic hygromas that are diagnosed prenatally generally have a poorer prognosis than those diagnosed after birth. The management of cystic hygramas, particularly those diagnosed prenatally, represents a persistent challenge in low-resourced settings. Counseling and treatment recommendations must be tailored based on tumor characteristics, the expected prognosis, and the feasibility of medical or surgical intervention in a given clinical environment.

CT findings of an incidental segmental aplasia of the caudal vena cava with azygos continuation in a guinea pig (Cavia porcellus).

Background: Segmental aplasia of the caudal vena cava (CVC) with azygos continuation is a congenital malformation macroscopically described in mammals including humans, dogs, and rodents. It is usually detected as an incidental finding and the final diagnosis is reached by computed tomography (CT), fluoroscopy, or post-mortem dissection. Case Description: A 3-year-old guinea pig (Cavia porcellus) presented with subacute dyspnea. A computed tomographic examination was performed for the evaluation of subtle pulmonary changes previously suspected on conventional radiography, and a segmental aplasia of the CVC with azygos continuation was identified as an incidental finding. Conclusion: According to database negative results, this is the first report describing a segmental aplasia of the CVC and azygos continuation in a guinea pig by CT.

Sirenomelia or mermaid syndrome with a cleft lip in a Tanzanian newborn: a case report.

BACKGROUND: Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized by partial or complete fusion of lower extremities, renal agenesis, absent urinary tract, ambiguous external genitalia, imperforate anus, and single umbilical artery. Sirenomelia is often associated with several visceral congenital malformations, rendering it invariably incompatible with extrauterine life. CASE PRESENTATION: We present the case of 22-year-old Black African woman who delivered a term newborn by caesarean section at a gestation age of 37 weeks due to obstructed labor with fetal distress. The newborn was a fresh stillbirth weighing 2100 g and had fusion of the lower extremities, a single upper limb, ambiguous genitalia, imperforate anus, and a cleft lip. The mother had made only two prenatal visits, at which she was found to be normotensive and normoglycemic. She was not screened for routine fetomaternal infections and missed supplementation for folic acid during the critical first trimester. She did not undergo any obstetric ultrasonography. The parents of the newborn were not close relatives and there was no family history of consanguinity. Further genetic testing was not performed due to lack of laboratory capacity, and post mortem examination was not permitted due to cultural taboo and restrictions relating to handling of deceased newborns. CONCLUSION: Sirenomelia is a rare congenital malformation with very poor prognosis. Specific interventions during pre-conception and early prenatal care are critical in the prevention of specific congenital anomalies. Early obstetric ultrasonography is invaluable for diagnosis of sirenomelia as well as counseling for possible termination of pregnancy.

The Approach to a Child with Dysmorphic Features: What the Pediatrician Should Know.

The advancement of genetic knowledge and the discovery of an increasing number of genetic disorders has made the role of the geneticist progressively more complex and fundamental. However, most genetic disorders present during childhood; thus, their early recognition is a challenge for the pediatrician, who will be also involved in the follow-up of these children, often establishing a close relationship with them and their families and becoming a referral figure. In this review, we aim to provide the pediatrician with a general knowledge of the approach to treating a child with a genetic syndrome associated with dysmorphic features. We will discuss the red flags, the most common manifestations, the analytic collection of the family and personal medical history, and the signs that should alert the pediatrician during the physical examination. We will offer an overview of the physical malformations most commonly associated with genetic defects and the way to describe dysmorphic facial features. We will provide hints about some tools that can support the pediatrician in clinical practice and that also represent a useful educational resource, either online or through apps downloaded on a smartphone. Eventually, we will offer an overview of genetic testing, the ethical considerations, the consequences of incidental findings, and the main indications and limitations of the principal technologies.

Lung Underdevelopment: Case Reports and a Literature Review.

Lung underdevelopment is a rare congenital anomaly with variable clinical significance and presenting symptoms. It usually manifests during childhood. We present two cases of developmental lung anomaly subtypes and discuss clinical presentation and outcomes in such patient populations. LEARNING POINTS: Pulmonary underdevelopment is a challenging diagnosis and should be considered in patients with unilateral opacification on chest radiograph.Childhood developmental history is critical for diagnosis as delayed, or misdiagnoses are common. Definitive diagnosis can be made by computed tomography scan.Management is watchful waiting with close monitoring, with long term prognosis remaining unclear.

Incidental diagnosis of silent extrahepatic portosystemic shunt.

Extrahepatic portosystemic shunts are a very rare disease. Early diagnosis and appropriate treatment are needed to prevent serious complications. In asymptomatic patients, conservative treatment is an option.

A rare tale of an extralobar pulmonary sequestration as a cause of hemoptysis not often contemplated: a case report.

Background: A rare congenital malformation of the respiratory tract, bronchopulmonary sequestration (BPS), may present symptomatically early on in childhood or adolescent years. Adult BPS is typically an incidental finding found on thoracic imaging. There are currently four known types of BPS. Intralobar sequestrations (ILSs) are the most common of them and the most commonly reported form in literature. In our case report, we report of a healthy adult female who presented with hemoptysis that resulted in the diagnosis of the rarest form of BPSs; extralobar sequestration (ELS). One that is not commonly described in literature, especially of one reported in late adulthood. This case report aims to educate and elude clinicians to this rare cause as a differential and guidance on its investigation and management. Case Description: In this case report, a 56-year-old woman who presented to an outpatient respiratory clinic after being referred by her general practitioner (GP) of a queried BPS. A thorough workup was done by the respiratory team that derived at the final diagnosis of an ELS. The patient's autonomy was adhered to along with risks and benefits which resulted in a non-surgical approach to management. One that she remarkably achieved a resolution of her symptoms. Conclusions: An awareness and familiarity of this rare disease, ELS, should prompt one to consider its' diagnosis when no other common causes are apparent. Often the diagnosis can be made radiologically. Treatment of ELSs should depend on multiple factors.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). METHODS: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. RESULTS: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. CONCLUSIONS: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.

Fbrsl1 is required for heart development in Xenopus laevis and de novo variants in FBRSL1 can cause human heart defects.

De novo truncating variants in fibrosin-like 1 (FBRSL1), a member of the AUTS2 gene family, cause a disability syndrome, including organ malformations such as heart defects. Here, we use Xenopus laevis to investigate whether Fbrsl1 plays a role in heart development. Xenopus laevis fbrsl1 is expressed in tissues relevant for heart development, and morpholino-mediated knockdown of Fbrsl1 results in severely hypoplastic hearts. Our data suggest that Fbrsl1 is required for the development of the first heart field, which contributes to the ventricle and the atria, but not for the second heart field, which gives rise to the outflow tract. The morphant heart phenotype could be rescued using a human N-terminal FBRSL1 isoform that contains an alternative exon, but lacks the AUTS2 domain. N-terminal isoforms carrying patient variants failed to rescue. Interestingly, a long human FBRSL1 isoform, harboring the AUTS2 domain, also did not rescue the morphant heart defects. Thus, our data suggest that different FBRSL1 isoforms may have distinct functions and that only the short N-terminal isoform, appears to be critical for heart development.