Malformations In Patients Research Articles

Arnold-Chiari Malformations in Pediatric Patients After Fetal Surgery for Meningomyelocele.

(1) Background: Fetal surgery for meningomyelocele (MMC) should reduce the occurrence of Arnold-Chiari malformations, hydrocephalus, the associated need for craniocervical decompression, and the need for cerebrospinal fluid shunt insertion. Fetal surgery should improve ambulatory status. (2) Methods: We used retrospective analysis of the documentation and descriptive statistics to summarize the clinical data and measured MRI parameters. The neurosurgical results are presented as the frequency of findings in percentages and compared with the results of the Management of Myelomeningocele Study (MOMS). (3) Results: A total of eight patients who underwent prenatal correction of MMC between 2016 and 2020 participated. MRI detected Chiari II malformation in all patients during prenatal imaging and in 87.5% of the patients at the age of 12 months. Craniocervical decompression was used in 25% of the patients. Shunt-dependent hydrocephalus occurred in 50% of the cases. In 87.5% of the cases, the functional level exceeded the expected ambulatory status. (4) Conclusions: We present the clinical status of our patients. Analysis of the complete cohort confirmed that prenatal surgery is associated with a reduced occurrence of Chiari malformations and reduced associated occurrence of hydrocephalus. Specific lesion levels are not associated with the need for craniocervical decompression. The results of our study are valuable in prenatal counseling and important for treatment planning.

Treatment of iliac arteriovenous malformation associated with trisomy 21: a case report

Both arteriovenous malformation (AVM) and trisomy 21 are rare diseases. Studies have shown that individuals with trisomy 21 may have potential vascular malformations, with the main site of onset being the portal system. This case involved an adult patient with trisomy 21 who presented with pelvic iliac arteriovenous malformations. The patient underwent interventional treatment, and the prognosis was favorable. It is important to enhance the screening for vascular malformations in patients with trisomy 21 syndrome. At the same time, interventional treatment for AVMs is effective and increasingly important for managing AVMs.

6912 Nail Fold Capillary Findings In Patients With Somatic EPAS1 Pathogenic Variants

Abstract Disclosure: H. Alkaissi: None. B. Turturice: None. J.S. Rosenblum: None. A.S. Alzahrani: None. S. Talvacchio: None. A. Derkyi: None. M. Nazari: None. H. Wang: None. I. Pinal Fernandez: None. Z. Zhuang: None. K. Pacak: None. We recently discovered a new syndrome characterized by a triad of pheochromocytoma/paraganglioma, polycythemia, and somatostatinoma (so called Pacak-Zhuang syndrome) caused by somatic gain-of-function pathogenic variants in the EPAS1 gene, encoding hypoxia-inducible factor 2α (HIF-2α). Recently, we have described additional features of this syndrome, including systemic developmental vascular malformations in patients and the mouse model [1]. Here we evaluated vascular changes in the nailfold capillaries by using video capillaroscopy in four patients, three of whom were female and carried the same pathogenic somatic EPAS1 variant allele (EPAS1A530V). The first patient is an 18-year-old female with a history of ventricular septal defect since birth, acrocyanosis, abdominal paraganglioma, left adrenal pheochromocytoma, and polycythemia. The second patient is a 64-year-old female who presented with paraganglioma without polycythemia, in whom we found the EPAS1A530V variant from hair sample, and an additional variant (EPAS1P53[1]A) in a resected paraganglioma, confirming the diagnosis. The third patient is a 33-year-old female had polycythemia, right adrenal pheochromocytoma, abdominal paragangliomas and duodenal somatostatinoma. The fourth patient is a 25-year-old male with PZS bearing a somatic EPAS1M535V pathogenic variant and an additional D536_L542 deletion, with hypoplastic left ventricle and metastatic paraganglioma who never developed polycythemia due to concomitant sickle cell-thalassemia traits. Despite the notable differences in genotype between the first three patients compared to the fourth patient, whose genotype is more complex, nailfold video capillaroscopy of all these patients showed similar phenotype—abnormal capillary structure marked by widespread dilations, megacapillaries, sporadic capillary hemorrhages, and regions with diminished capillary density. While polycythemia has been implicated in megacapillaries phenotype, two of our patients did not have polycythemia at the time of evaluation, further supporting the role of HIF-2a in angiogenesis. In conclusion, we describe nailfold capillary changes on video capillaroscopy as a non-invasive clinical sign in patients with EPAS1 pathogenic variants. Whether this finding is due to circulating angiogenic factors secreted by the tissues harboring HIF-2α mutation, or a direct effect of HIF-2α on angiogenesis remains to be determined.

Multimodal ultrasound imaging for patent foramen ovale and pulmonary arteriovenous malformation in patients with cryptogenic stroke or migraine: A prospective diagnostic study.

Right-to-left shunt (RLS) caused by patent foramen ovale (PFO) and pulmonary arteriovenous malformations (PAVM) have been associated with a variety of diseases, and reliable techniques for detecting RLS are essential for diagnosis. This study aimed to compare the diagnostic accuracy of multimodal ultrasound imaging, including transthoracic echocardiography (TTE) plus contrast transthoracic echocardiography (CTTE) and transesophageal echocardiography (TEE) plus contrast transesophageal echocardiography (CTEE) for PFO and PAVM in patients with cryptogenic stroke or migraine. This prospective study enrolled patients with cryptogenic stroke or migraine admitted to First Hospital of Shanxi Medical University between July 2018 and April 2023. The TTE + CTTE + TEE + CTEE multimodal ultrasound imaging was defined as the gold standard. A total of 230 patients with cryptogenic stroke (108) or migraine (122) were enrolled. The TEE + CTEE generated a better area under the receiver operator characteristic (ROC) curves (AUC) than TTE + CTTE [0.995 (0.988-1.000) vs 0.975 (0.767-0.984), P < .001], indicating better identification of PFO and PAVM. The sensitivity and specificity of the TTE + CTTE were 89.4% and 85.7%, respectively, whereas the sensitivity and specificity of TEE + CTEE were 99.1% and 100%, respectively. The missed diagnosis rate of TTE + CTTE and TEE + CTEE was 65.7 % and 12.5%, respectively. The combination of TEE + CTEE may be a more reliable and sensitive tool to detect PFO and PAVM than TTE + CTTE in patients with cryptogenic stroke or migraine.

Arterial Spin-Labeling MR Imaging in the Detection of Intracranial Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that causes vascular malformations in a variety of organs and tissues, including brain AVMs. Because brain AVMs have the potential to cause disabling or fatal intracranial hemorrhage, detection of these lesions before rupture is the goal of screening MR imaging/MRA examinations in patients with HHT. Prior studies have demonstrated superior sensitivity for HHT-related brain AVMs by using postcontrast MR imaging sequences as compared with MRA alone. We now present data regarding the incremental benefit of including arterial spin-labeling (ASL) perfusion sequences as part of MR imaging/MRA screening in patients with this condition. We retrospectively analyzed 831 patients at the UCSF Hereditary Hemorrhagic Telangiectasia Center of Excellence. Of these, 42 patients had complete MR imaging/MRA, ASL perfusion scans, and criterion-standard DSA data. Two neuroradiologists reviewed imaging studies and a third provided adjudication when needed. Eight patients had no brain AVMs detected on DSA. The remaining 34 patients had 57 brain AVMs on DSA. Of the 57 identified AVMs, 51 (89.5%) were detected on ASL and 43 (75.4%) were detected on conventional MR imaging/MRA sequences (P = .049), with 8 lesions detected on ASL perfusion but not on conventional MR imaging. ASL provides increased sensitivity for brain AVMs in patients with HHT. Inclusion of ASL should be considered as part of comprehensive MR imaging/MRA screening protocols for institutions taking care of patients with HHT.

Characteristics and Clinical Features of Anorectal Malformations Without Fistula: A Systematic Literature Review

Anorectal malformation (MA) without fistula is a form of congenital abnormality that is often found in newborn babies. This study aims to identify the characteristics and clinical features of MA without fistula based on the latest scientific evidence. A systematic search was conducted on the PubMed, Scopus, and Web of Science databases using relevant keywords. Inclusion criteria included observational studies reporting the characteristics and clinical features of MA without fistula in humans. Two independent researchers conducted study selection, data extraction, and study quality assessment using the JBI Critical Appraisal Checklist tool. A total of 25 studies (2018-2024) involving 1548 MA patients without fistula met the inclusion criteria. The majority of patients were male (62%). The average age at diagnosis is 2 days. The most frequently reported clinical symptoms were absence of anus (100%), abdominal distension (78%), and vomiting (65%). The most common classification of MA without fistula was perineal (45%), followed by vestibular (30%) and cloacal (25%). The most frequently performed definitive surgery was perineal anoplasty (55%), followed by posterior sagittal anorectoplasty (PSARP) (35%) and laparoscopic-assisted anorectoplasty (10%). The most frequently reported postoperative complications were anal stenosis (15%), surgical wound infection (10%), and rectal prolapse (5%). MA without fistula is more common in male babies. The main clinical symptoms are absence of anus, abdominal distension, and vomiting. The perineal classification is the most common. Perineal anoplasty is the most frequently performed definitive surgery. Post-operative complications that need to be watched out for are anal stenosis, surgical wound infection, and rectal prolapse.

Identification and Analysis of Atrial-Bronchial-Abdominal Disharmony in Patients with Isomeric Atrial Appendages.

Ideally, the morphology of atrial appendages should solely be used to identify and differentiate patients with isomeric right and left atrial appendages. However, in clinical practice, the segregation is often indirectly based on the arrangement of thoraco-abdominal structures. The correlation between thoraco-abdominal arrangement and atrial appendages, however, is imperfect. In this study, we sought to clarify the cardiovascular malformations in patients with isomeric atrial appendages with an emphasis on atrial-thoracic-abdominal disharmony. A retrospective review of all patients who underwent cardiac CT angiography between January 2014 and June 2023 and identified to have isomeric atrial appendages was performed. Of the 366 cases (median age: 2years [interquartile range: 11months-7years]), 247 (67.5%) patients had isomeric right atrial appendages while 119 (32.5%) patients had isomeric left atrial appendages. In 316 (86.3%) patients, the thoraco-abdominal arrangement was as per atrial appendage morphology while the remaining 50 (13.6%) patients had disharmonious patterns. Compared to isomeric left atrial appendages, the disharmonious pattern was more frequent with isomeric right atrial appendages (5.9% vs. 17.4%; p 0.003). Irrespective of the type of isomerism, disharmony was mostly confined to the level of the abdomen. Not all patients with isomeric atrial appendages have a harmonious thoraco-abdominal arrangement. The atrial-bronchial-abdominal disharmony is more frequent with isomeric right atrial appendages and is mostly present at the level of the abdomen. A detailed sequential segmental analysis with an independent description of each organ system is, therefore, essential for the complete evaluation of patients with isomeric atrial appendages.

Surgical treatment of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia: a single-center experience.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder characterized by multiple vascular malformations. Brain arteriovenous malformations (bAVMs) are a significant manifestation of HHT. The surgical management of these lesions in patients with HHT remains debated, with limited literature on postoperative outcomes. The goal of this study was to evaluate the safety and efficacy of surgical treatment for bAVMs in patients with HHT and propose a treatment rationale based on a single-center experience. This retrospective review included 20 patients diagnosed with HHT who underwent resection of 23 bAVMs at the Stanford University Medical Center between January 2007 and September 2023. Data were also collected on bAVMs treated conservatively, with embolization, or with radiosurgery at the authors' institution, for comparison. There were 16 Spetzler-Martin (SM) grade I, 6 SM grade II, and 1 SM grade IV bAVM. Six of the bAVMs presented with neurological symptoms (3 with hemorrhage and 3 with focal neurological deficits), while the rest were detected on routine screening. Complete excision was angiographically confirmed in all patients, with a mean overall hospital stay of 2.1 days and a mean follow-up of 36 months. Postoperative complications were limited to transient mild weakness in 2 patients, 1 of whom also had transient speech deficits, and visual field deficits in 3 patients, 2 of whom improved on long-term follow-up. In this most extensive surgical series published to date, resection of bAVMs in patients with HHT showed favorable outcomes with a low complication rate, suggesting that the benefits of surgery outweigh the risks, especially considering the potential cumulative lifetime risk of hemorrhage. MR arterial spin labeling was found to be the most sensitive noninvasive measure of detecting bAVMs in patients with HHT.

Angiographic tool to detect pulmonary arteriovenous malformations in single ventricle physiology.

Individuals with single ventricle physiology who are palliated with superior cavopulmonary anastomosis (Glenn surgery) may develop pulmonary arteriovenous malformations. The traditional tools for pulmonary arteriovenous malformation diagnosis are often of limited diagnostic utility in this patient population. We sought to measure the pulmonary capillary transit time to determine its value as a tool to identify pulmonary arteriovenous malformations in patients with single ventricle physiology. We defined the angiographic pulmonary capillary transit time as the number of cardiac cycles required for transit of contrast from the distal pulmonary arteries to the pulmonary veins. Patients were retrospectively recruited from a single quaternary North American paediatric centre, and angiographic and clinical data were reviewed. Pulmonary capillary transit time was calculated in 20 control patients and compared to 20 single ventricle patients at the pre-Glenn, Glenn, and Fontan surgical stages (which were compared with a linear-mixed model). Correlation (Pearson) between pulmonary capillary transit time and haemodynamic and injection parameters was assessed using angiograms from 84 Glenn patients. Five independent observers calculated pulmonary capillary transit time to measure reproducibility (intraclass correlation coefficient). Mean pulmonary capillary transit time was 3.3 cardiac cycles in the control population, and 3.5, 2.4, and 3.5 in the pre-Glenn, Glenn, and Fontan stages, respectively. Pulmonary capillary transit time in the Glenn population did not correlate with injection conditions. Intraclass correlation coefficient was 0.87. Pulmonary angiography can be used to calculate the pulmonary capillary transit time, which is reproducible between observers. Pulmonary capillary transit time accelerates in the Glenn stage, correlating with absence of direct hepatopulmonary venous flow.

Genital Malformations in Children With VACTERL – Has Time Come to Include “G” in the Acronym?

BackgroundGenital malformations are frequently diagnosed in patients with VACTERL, but are currently not included in the acronym. This study aimed to analyze the frequency of genital anomalies in patients with esophageal atresia (EA) and/or anorectal malformation (ARM), with a subgroup analysis of children fulfilling the VACTERL criteria. MethodThis was a cross-sectional retrospective analysis of two prospectively collected registries of patients operated on for ARM and EA between 2012 and 2022 at a specialized national center. Children were screened routinely for malformations according to the VACTERL acronym. ResultsA total of 174 children were included in the study. VACTERL was diagnosed in 60 children (34%), while 114 children (66%) were defined as non-VACTERL. Genital malformations were diagnosed in 38% (23/60) of the children with VACTERL, and in 11% (13/114) of the children without VACTERL (p < 0.001). The presence of genital malformations correlated linearly with the number of diagnosed component features (CFs). In boys with VACTERL, the most common genital malformation was undescended testes present in 10/27 (21%) compared to 1/71 (1%) in non-VACTERL boys (p < 0.001). Müllerian duct anomalies were found in 26% of girls with VACTERL vs. 7% in non-VACTERL girls (p < 0.05). ConclusionThere was a higher frequency of genital malformations in patients with VACTERL emphasizing the importance of genital assessment for these patients. We propose VACTERL-G as an extension of the current acronym aiming to reduce the risk of long-term morbidity due to delayed diagnosis of reproductive anomalies. Level of Evidence4.

Computed tomography multi-planar and 3D image assessment protocol for detailed analysis of inner ear malformations in patients undergoing cochlear implantation counseling.

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Congenital inner ear malformations resulting from embryogenesis may be visualized in radiological scans. Many attempts have been made to describe and classify the defects of the inner ear based on anatomical and radiological findings.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; The aim was to propose and discuss computed tomography multi-planar and 3D image assessment protocols for detailed analysis of inner ear malformations in patients undergoing cochlear implantation counseling.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Material and methods:&lt;/b&gt; A retrospective analysis of 22 malformed inner ears. CT scans were analyzed using the Multi-Planar Reconstruction (MPR) option and 3D reconstruction.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; The protocol of image interpretation was developed to allow reproducibility for evaluating each set of images. The following malformations were identified: common cavity, cochlear hypoplasia type II, III, and IV, incomplete partition type II and III, and various combinations of vestibule labyrinth malformations. All anomalies have been presented and highlighted in figures with appropriate descriptions for easier identification. Figures of normal inner ears were also included for comparison. 3D reconstructions for each malformation were presented, adding clinical value to the detailed analysis.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; Properly analyzing CT scans in cochlear implantation counseling is a necessary and beneficial tool for appropriate candidate selection and preparation for surgery. As proposed in this study, the unified scans evaluation scheme simplifies the identification of malformations and reduces the risk of omitting particular anomalies. Multi-planar assessment of scans provides most of the necessary details. The 3D reconstruction technique is valuable in addition to diagnostics influencing the decision-making process. It can minimize the risk of misdiagnosis. Disclosure of the inner ear defect and its precise imaging provides detailed anatomical knowledge of each ear, enabling the selection of the appropriate cochlear implant electrode and the optimal surgical technique.&lt;/br&gt.

Zebrafish as a model to investigate a biallelic gain-of-function variant in MSGN1, associated with a novel skeletal dysplasia syndrome

Background/ObjectivesRare genetic disorders causing specific congenital developmental abnormalities often manifest in single families. Investigation of disease-causing molecular features are most times lacking, although these investigations may open novel therapeutic options for patients. In this study, we aimed to identify the genetic cause in an Iranian patient with severe skeletal dysplasia and to model its molecular function in zebrafish embryos.ResultsThe proband displays short stature and multiple skeletal abnormalities, including mesomelic dysplasia of the arms with complete humero-radio-ulna synostosis, arched clavicles, pelvic dysplasia, short and thin fibulae, proportionally short vertebrae, hyperlordosis and mild kyphosis. Exome sequencing of the patient revealed a novel homozygous c.374G > T, p.(Arg125Leu) missense variant in MSGN1 (NM_001105569). MSGN1, a basic-Helix–Loop–Helix transcription factor, plays a crucial role in formation of presomitic mesoderm progenitor cells/mesodermal stem cells during early developmental processes in vertebrates. Initial in vitro experiments show protein stability and correct intracellular localization of the novel variant in the nucleus and imply retained transcription factor function. To test the pathogenicity of the detected variant, we overexpressed wild-type and mutant msgn1 mRNA in zebrafish embryos and analyzed tbxta (T/brachyury/ntl). Overexpression of wild-type or mutant msgn1 mRNA significantly reduces tbxta expression in the tailbud compared to control embryos. Mutant msgn1 mRNA injected embryos depict a more severe effect, implying a gain-of-function mechanism. In vivo analysis on embryonic development was performed by clonal msgn1 overexpression in zebrafish embryos further demonstrated altered cell compartments in the presomitic mesoderm, notochord and pectoral fin buds. Detection of ectopic tbx6 and bmp2 expression in these embryos hint to affected downstream signals due to Msgn1 gain-of-function.ConclusionIn contrast to loss-of-function effects described in animal knockdown models, gain-of-function of MSGN1 explains the only mildly affected axial skeleton of the proband and rather normal vertebrae. In this context we observed notochord bending and potentially disruption of pectoral fin buds/upper extremity after overexpression of msgn1 in zebrafish embryos. The latter might result from Msgn1 function on mesenchymal stem cells or on chondrogenesis in these regions. In addition, we detected ectopic tbx6 and bmp2a expression after gain of Msgn1 function in zebrafish, which are interconnected to short stature, congenital scoliosis, limb shortening and prominent skeletal malformations in patients. Our findings highlight a rare, so far undescribed skeletal dysplasia syndrome associated with a gain-of-function mutation in MSGN1 and hint to its molecular downstream effectors.

Pulmonary arteriovenous malformations in patients with previous brain abscess: a cross-sectional population-based study.

Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right-to-left shunts was also assessed post hoc. This was a cross-sectional population-based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble-echocardiography to detect vascular right-to-left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble-echocardiography. The median age of participants was 54 years (IQR 45-62) and 19/57 (33%) were females compared with 59 years (IQR 48-68, p = 0.05) and 41/85 females (48%, p = 0.22) in non-participants. Bubble-echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06-11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right-to-left shunts amongst brain abscess patients corresponds to the prevalence in the general population.

#382 : Congenital Adrenal Hyperplasia with Concomitant Mullerian Agenesis: A Rare Occurance in 46 XX Disorders of Sexual Development (DSD)

Background and Aims: The most common cause of 46 XX DSD is due to congenital adrenal hyperplasia with varying degree of virilization. Females with CAH do not produce anti mullerian hormone (AMH), therefore the internal genitalia, which are mullerian derivatives, are develop normally. We report a unique case of CAH with absent uterus, cervix, and fallopian tube. Method: The clinical, laboratory, and imaging findings of the patient are presented with literature review. Results: We report an ongoing case of a 20-year-old patient with ambiguous genitalia and primary amenorrhea. She was born from a healthy mother and raised as a female. There was no family history of the same disorder. On physical examination we found that she had normal height, normal blood pressure, palatoschizis, undeveloped breast (Tanner stage 1), and clitoral virilization with single urovaginal opening (Prader stage 3). We performed a G-Banded chromosome analysis, with 46 XX results. Laboratory test showed her 17-hidroxyprogesterone level was 176,93 ng/ml, FSH level was 3,06 mIU/ml, LH level was 2,21 mIU/ml, and estradiol level was 18,0 pg/mL. Ultrasound imaging revealed the absence of uterus, cervix, and vagina, as well as abnormal appearance of ovarium. We have planned to perform a complete MRI study for other anomalies as we suspected this patient had Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome type II. Conclusion: In the presence of external genitalia and urinary tract malformations in patients with CAH, it is important to investigate for possible associated mullerian anomalies. A comprehensive approach in diagnosis could lead to a better outcome in a patient’s treatment and wellbeing.

Direct Transverse Sinus Puncture for Transvenous Coil Embolization of Vein of Galen Malformations: Innovating Existing Techniques.

Vein of Galen malformations (VOGMs) are complex arteriovenous malformations in neonates and young children. Recent advances in endovascular interventions have drastically improved treatment and clinical outcomes in what was previously high-morbidity, high-mortality disease. The high-flow shunt pathophysiology in VOGMs can lead to dynamic changes in the malformation angioarchitecture, and over time patients can develop jugular bulb stenosis. In the setting of inaccessible transvenous access to the malformation for endovascular embolization in cases where transarterial embolization is inadequate, a combined surgical and endovascular technique must be used. We present the first successful modern-day application of direct puncture through transverse sinus for transvenous embolization of a VOGM. We present 2 unique cases of complex VOGM malformations in patients who had previously undergone staged endovascular embolization for reduction of flow within the malformation. On follow-up, in both cases, there was development of severe sigmoid sinus and jugular bulb stenosis, increasing intracranial venous congestion and causing marked clinical deterioration. The stenosis prevented traditional transvenous access and treatment. We describe a direct puncture transverse sinus access using a burr hole approach for endovascular transvenous embolization in both cases with successful clinical outcomes. Direct access using burr hole craniotomy to the transverse sinus for transvenous endovascular embolization is a safe approach in the setting of severe jugular bulb stenosis for treatment of VOGMs. This technique can be done efficiently to achieve complete flow elimination in the malformation, in cases where that is called for, without significant risks or complications related to the approach.

Profile of cardiac lesions among laboratory confirmed congenital rubella syndrome (CRS) infants: a nationwide sentinel surveillance, India, 2016-22.

The phenotypical profile of cardiovascular malformations in patients with congenital rubella syndrome (CRS) is varied. We aimed to describe the profile of cardiac defects among CRS patients detected in the sentinel CRS surveillance in India during 2016-22. Sentinel sites enrolled infants with suspected CRS based on presence of cardiac defects, hearing impairment, eye signs, or maternal history of febrile rash illness. Suspected CRS cases underwent detailed systemic examination, including echocardiography and serological investigation for rubella. Cardiac defects were categorized as 'Simple' or 'Complex' as per the National Heart, Lung, and Blood Institute classification. We compared the distribution of cardiac defects among laboratory confirmed CRS cases and seronegative discarded cases. Of the 4578 suspected CRS cases enrolled by 14 sites, 558 (12.2%) were laboratory confirmed. 419 (75.1%) laboratory confirmed cases had structural heart defects (simple defects: n=273, 65.2%, complex defects: n=144, 34.4%), with ventricular septal defect (42.7%), atrial septal defect (39.4%), patent ductus arteriosus (36.5%), and tetralogy of Fallot as the commonest defects (4.5%). Laboratory confirmed CRS cases had higher odds of left to right shunt lesions (OR=1.58, 95% CI: 1.15-2.17). This was mainly on account of a significant association of PDA with CRS (OR=1.77, 95% CI: 1.42-2.21). Mortality was higher among CRS patients with complex heart defects (HR=2.04, 95% CI: 1.26-3.30). Three-fourths of the laboratory confirmed CRS cases had structural heart defects. CRS patients with complex cardiac defects had higher mortality. Detecting CRS infection early and providing timely intervention for cardiovascular defects is critical for the management of CRS patients. Ministry of Health and Family Welfare, Govt of India, through Gavi, the Vaccine Alliance.

Heterogeneity of Orofacial Clefts and Associated Anomalies in China.

Despite the large number of affected individuals in China, information on the descriptive epidemiology of orofacial clefts in the Chinese population remains limited. Therefore, the authors aimed to report a detailed clinical classification of orofacial clefts, including microform cleft lip (CL), and associated malformations in patients from a major cleft surgical unit in China. The authors reviewed the medical records of 718 patients who underwent primary cleft repair surgery at their center between December 2016 and April 2023. The sex distribution varied with cleft type and extent, and males had a higher proportion of clefts with increased severity than females. In patients with a unilateral CL, the ratio of left-to-right-sided clefts was 1.85:1. The frequency of associated congenital malformations in patients with microform CL only, overt CL only, CL and palate, and cleft palate only was 8.0%, 7.6%, 14.9%, and 30.9%, respectively. A total of 98 malformations were observed in 69 patients with congenital anomalies of unknown origin. Among these, cardiovascular anomalies were the most common, identified in 27 patients (39.1%), followed by head and neck and musculoskeletal anomalies. The high risk of heart defects highlights the importance of routine echocardiography. Microform CL exhibited increased prevalence and a similar frequency of associated malformations with overt CL, suggesting that this mild phenotype requires further attention by clinicians.

Prevalence of Retinal Venous Malformations in Patients With Cerebral Cavernous or Arteriovenous Malformations.

Cerebral vascular malformations (CVMs) may result in hemorrhage, seizure, neurologic dysfunction, and death. CVMs include capillary telangiectasias, venous malformations, cavernous malformations, and arteriovenous malformations. Cavernous and arteriovenous malformations carry the highest risk of complications. Retinal venous malformations (RVMs) have been proposed as an associated finding. Our objective was to determine the prevalence of RVMs in patients with high-risk CVMs. We retrospectively reviewed patients diagnosed with cerebral cavernous or arteriovenous malformations (high-risk CVMs) who were evaluated by the ophthalmology service at Northwestern University between 2017 and 2020. Patients were stratified into 3 cohorts based on level of certainty: dilated funduscopic examination (DFE), DFE with any form of ocular imaging, and DFE with complete imaging of the macula. We recorded ophthalmic examination abnormalities, ocular imaging findings, and major CVM complications. We evaluated 156 patients with high-risk CVMs who had undergone DFE. Ocular imaging of any type was performed in 56 patients, of whom 46 had complete imaging of the macula. Zero RVMs were identified in any cohort (95% confidence interval: 0%-1.9% for the entire cohort, 0%-5.4% for any ocular imaging cohort, and 0%-6.5% for the complete macular imaging cohort). Cerebral hemorrhage or seizure occurred in 15%-33% of patients. Associated visual field defects or cranial nerve palsies were found in 14%-20% of patients. Zero RVMs were identified in patients with high-risk CVMs. However, neuro-ophthalmic findings were common. Therefore, we recommend neuroimaging for patients with RVMs and neuro-ophthalmic signs or symptoms. In asymptomatic patients with RVMs, a potential algorithm for neuroimaging is proposed.

Identification of novel mutations in patients with Diamond-Blackfan anemia and literature review of RPS10 and RPS26 mutations.

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome characterized by erythroid aplasia, physical malformation, and cancer predisposition. Twenty ribosomal protein genes and three non-ribosomal protein genes have been identified associated with DBA. To investigate the presence of novel mutations and gain a deeper understanding of the molecular mechanisms of disease, targeted next-generation sequencing was performed in 12 patients with clinically suspected DBA. Literatures were retrieved with complete clinical information published in English by November 2022. The clinical features, treatment, and RPS10/RPS26 mutations were analyzed. Among the 12 patients, 11 mutations were identified and 5 of them were novel (RPS19, p.W52S; RPS10, p.P106Qfs*11; RPS26, p.R28*; RPL5, p.R35*; RPL11, p.T44Lfs*40). Including 2 patients in this study, 13 patients with RPS10 mutations and 38 patients with RPS26 mutations were reported from 4 and 6 countries, respectively. The incidences of physical malformation in patients with RPS10 and RPS26 mutations (22% and 36%, respectively) were lower than the overall incidence in DBA patients (~50%). Patients with RPS26 mutations had a worse response rate of steroid therapy than RPS10 (47% vs. 87.5%), but preferred RBC transfusions (67% vs. 44%, p = 0.0253). Our findings add to the DBA pathogenic variant database and demonstrate the clinical presentations of the DBA patients with RPS10/RPS26 mutations. It shows that next-generation sequencing is a powerful tool for the diagnosis of genetic diseases such as DBA.

Lower urinary tract dysfunction in cases of anorectal malformations

Association of genitourinary anomalies in patients with ano-rectal malformations (ARM) is well known and its incidence is reported to be 30 -50%. Many of these anomalies either have less number of functioning renal units or have conditions with risk of continuous damage to renal units, increasing the risk of developing End stage renal disease (ESRD) in adolescence or adulthood. Although frequently described as associated malformations but few of these entities like Vesico ureteric reflux (VUR) could be the result of lower urinary tract dysfunctions.: To study incidence and spectrum of Lower urinary tract dysfunction in toilet trained patients of ARM. To find whether LUTD is the cause of worsening of VUR/HUN/ renal functions in patients with ARM. 2 years (October 2018 to 30 September 2020): Department of Paediatric surgery, Chacha Nehru Bal Chikitsalaya, Geeta Colony Delhi Prospective observational study. : Forty-two patients of ARM, meeting all inclusion criteria were enrolled in the study. All the following criteria were checked for enrolment of patient in the study. 1. Patients of all categories of anorectal malformations who were toilet trained; 2. Age more than 4 years; 3. Completed set of investigations planned for diagnosis of LUTD. 4. Consented to participate in the study and for follow up as and when required.Central cause of neurological deficits.A total of 125 patients who underwent PSARP during our study period. However only 42 patients met the inclusion criteria and got their work up completed for urological problems. 1.LUTD and renal failure can be seen even in absence of spinal malformations in patients with ARM; 2. Severity of LUTD in absence of neurological involvement changes with time; 3. Thorough history and clinical evaluation may provide important clues in suspecting presence of occult LUTD.