Rare Malformation Research Articles

Alobar holoprosencephaly: A case report

Introduction: Holoprosencephaly (HPE) is a rare brain malformation, which results from a cleavage defect of the prosencephalon. Three forms have been described as: alobar, semi-lobar, and lobar forms. Case Report: We report a rare case of holoprosencephaly, diagnosed at the maternity of the Ibn Rochd Hospital Center in Casablanca. Conclusion: Holoprosencephaly is secondary to a cleavage anomaly of the prosencephalon, the diagnosis is based on echotomography, computed tomography (CT) scan and nuclear magnetic resonance imaging (MRI). It is important to perform a karyotype to look for a chromosomal anomaly. Holoprosencephaly, although rare, should be recognized and diagnosed; minor forms are likely to benefit from medical replacement therapy or ventricular shunting.

A case of successful treatment of an isolated tracheoesopha- geal fistula in a 2-month-old child

Isolated tracheoesophageal fistula is a very rare malformation, which is a pathological communication between the walls of the esophagus and the trachea. The entry of food into the trachea causes severe obstructive and ventilatory disorders in infants. Surgical treatment of developmental anomalies includes open thoracic or transsternal access, which is traumatic, often complicated by pleurisy and mediastinitis in the postoperative period and long-term musculoskeletal deformities. Purpose. To demonstrate the effectiveness of minimally invasive surgery in the correction of this defect. Fibro-tracheo-bronchoscopy confirmed an isolated tracheoesophageal fistula in a 2-month-old child. Thoracoscopic intervention using 3 ports was chosen and performed as a surgical method of treatment. A large tracheoesophageal fistula, up to 10 mm, was found. The tracheal end of the fistula was sutured with 2 ligatures, tied and cut off. The defect in the wall of the esophagus was hermetically sutured. The postoperative period proceeded without complications. Enteral nutrition through the nipple started on the 10th day. Control examination after 1 and 6 months: the child has no anxiety; psychomotor development corresponds to age, on esophagoscopy the esophagus is freely passable, constrictions and defects were revealed . Conclusion. The high resolution and ergonomics of modern endoscopic equipment made it possible to visualize the malformation in an infant in detail, to separate pathological communication with minimal trauma and to avoid early and long-term complications.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

BackgroundKlippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS.ResultsParticipants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1.ConclusionsThe PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

A case report of prenatal diagnostics and surgical correction of pulmonary agenesis associated with total anomalous pulmonary venous connection and vascular ring

Abstract Pulmonary agenesis is a rare malformation associated with congenital heart disease and may lead to a life-threatening condition and death without pre-planned surgical and medical support. We report an unusual case of unilateral pulmonary agenesis in combination with total anomalous pulmonary venous connection, complete vascular ring, retroaortic, retroesophageal innominate vein, secondary atrial septal defect, which was prenatally identified by fetal ultrasound and magnetic resonance imaging, later confirmed by postnatal computed tomography.

Analysis of the distribution and orientation of oxygenated and non-oxygenated blood in a double outlet right ventricle

Double outlet right ventricle (DORV) is a malformation of the fetal heart in utero that affects the ventricular chambers. It usually presents with a displacement of the aorta and more than half the circumference of both arterial valves in the right ventricle. A peculiar characteristic is given by an interventricular septal defect (VSD), which allows communication between the left ventricle and the right with consequent mixing of oxygenated and non-oxygenated blood inside the cavities. A crucial question in assessing the degree of severity of functional dysfunction concerns the percentage of oxygenated blood that is ejected into the primary circulation via the aorta, a result that depends on the details of the vortex flow pattern within the two ventricular chambers. This study analyzes a complete DORV case through the use of numerical simulations that allow to identify the concentrations of oxygenated and non-oxygenated blood passing through this geometry. Results show that the VSD presents a significant impact on the fluid dynamic performance of the two ventricles. The analysis of blood concentration allowed to quantify the presence of oxygenated blood ejected into the pulmonary artery and of non-oxygenated blood into the aortic artery. The analysis of this specific case aims to demonstrate how the fluid dynamics analysis of this rare malformation, properly coupled with imaging technology, can provide information that could not be obtained otherwise and that are relevant for a careful clinical management including timely therapeutic intervention.

Verification of the efficacy of topical sirolimus gel for systemic rare vascular malformations: a pilot study.

Numerous clinical trials of sirolimus, an inhibitor of mechanistic/mammalian target of rapamycin complex 1, for the treatment of vascular malformations have been conducted. However, aside from lymphatic malformations, the efficacy of sirolimus for venous and capillary malformations has not been established. Moreover, no generalized venous or capillary malformations have been treated with topical sirolimus. To evaluate the safety and efficacy of topical sirolimus for venous and capillary malformations and to compare the efficacy of topical and systemic sirolimus therapy, an open-label single-arm pilot study with 0.2% sirolimus gel was conducted from July 19, 2019, to January 30, 2020, in four patients diagnosed with different vascular malformations (blue rubber bleb nevus syndrome, common venous malformation, phakomatosis pigmentovascularis type IVb, and angiokeratoma in Fabry disease). The primary endpoint was the safety evaluation of sirolimus gel. The main secondary endpoint was the improvement rate evaluated by the Central Judgment Committee at 12 weeks using photographs. No adverse events were observed. Blood sirolimus was not detected in any patient. Two patients (50%) had mild improvement, and the remaining two patients (50%) showed no change after 12 weeks of treatment. Blue rubber bleb nevus syndrome, a generalized venous malformation, showed the greatest response. In conclusion, 0.2% sirolimus gel was found to be as clinically effective as systemic sirolimus treatment in patients with venous and capillary malformations and more effective for early active lesions, even systemic venous malformations.

Successful non-surgical endodontic management of type III dens invaginatus by using cone-beam computed tomography: a case report

Dens invaginatus (DI) is a rare malformation of a tooth caused by the invagination of tooth crown before biological mineralization occurs. In DI type III invagination extends beyond the cementum-enamel junction, with the second foramen extending into the periapical tissues or into the periapical area. DI type III may pose real challenges for the clinician, especially when endodontic treatment is required. Objective: The present case report describes the successful non-surgical endodontic management of a tooth with DI type III with the aid of cone-beam computed tomography (CBCT). Case report: A 20-year-old male patient was referred for endodontic evaluation and treatment of the left maxillary lateral incisor (tooth #22), which presented a darker and unusual crown shape. Periapical radiography and CBCT scans revealed the presence of a type III DI, and a larger periapical lesion associated with external root resorption and discontinuous buccal cortical plate Results: The diagnosis of Oehlers type III DI with asymptomatic apical periodontitis was established, and non-surgical endodontic treatment was initiated. After 5 months, a decrease in the periapical lesion and arrest of external resorption was detected. The root canals were then filled, and the tooth restored. At the 3-years follow-up, clinical and imaging assessments revealed successful outcome of the treatment. Conclusion: CBCT is an inestimable tool for non-surgical endodontic management of teeth with complex internal anatomy, such as DI type III with associated large periapical lesion.

Surgical treatment of anomalous right upper lobe pulmonary vein obstruction caused by compression between pulmonary artery and trachea: a case report.

The normal anatomical course of right upper lobe pulmonary vein involves drainage anteriorly to the pulmonary artery, ultimately reaching the left atrium. However, anomalies can occur with the most common variation involving the convergence of the right upper lobe pulmonary vein with the superior vena cava. In a rare pulmonary vascular malformation, the anomalous right upper lobe pulmonary vein takes a path between the right pulmonary artery and right main bronchus [1]. During a clinical consultation, a patient presented in our hospital with this specific anomalous right upper lobe pulmonary vein, along with an atrial septal defect and a patent ductus arteriosus. As a consequence of this aberrant positioning, the right upper lobe pulmonary vein was compressed between the pulmonary artery and trachea, leading to pulmonary vein obstruction. Thus, a successful pulmonary vein replantation was performed to correct the congenital malformation.

Herlyn-Werner-Wunderlichov sindrom s piohematokolposom

Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare malformation syndrome of the women reproductive tract characterized by uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. We report here a case of a 20 year-old patient presented to the emergency department with pain in the right lower quadrant. The clinical exam showed a vaginal fluctuant painful mass obliterating the right part of the vagina. Transvaginal ultrasound showed uterus didelphys, the right uterus was dilated with a dense fluid collection which corresponded to pyohematometra. It also revealed a dense vaginal collection which corresponded to pyohematocolpos. Abdominal ultrasound showed the absence of a right kidney. The laparoscopy showed uterus didelphys with a large right uterus. We performed the resection of the vaginal septum to reconstruct one vagina. The first follow-up visit revealed a healthy wound with no adhesion of the vaginal wall. Prompt and accurate diagnosis of female reproductive tract disorders, including HWWS, is necessary to prevent complications and preserve future fertility.

Open surgical ligation of a thoracic spinal epidural arteriovenous fistula causing thoracic myelopathy: illustrative case.

Spinal epidural arteriovenous fistulas (eAVFs) are rare spinal vascular malformations characterized by an abnormal connection from the paraspinal and paravertebral system to the epidural venous plexus. This contrasts with the more frequently seen spinal dural AVF, where the fistula is entirely intradural. Although endovascular repair is commonly performed for spinal eAVF, few cases require open surgical ligation. The authors present a case of a 74-year-old male with progressive thoracic myelopathy secondary to a spinal eAVF. Thoracic magnetic resonance imaging (MRI) showed intramedullary T2 signal hyperintensity from T8 to T12. Spinal angiography revealed a primary arterial supply from the right T11 segmental artery and minor supply from the left T11 branches with drainage into the ventral epidural space. The patient underwent T11-12 laminectomy and complete right T11-12 facetectomy for ligation of the fistula with T11-L1 fusion. A postoperative spinal angiogram showed resolution of the fistula. Postoperatively, the patient's myelopathy improved, and MRI showed a decrease in T2 cord intensity. Spinal eAVFs are rare lesions that differ from the more commonly seen intradural dural AVF in that the abnormal connection is in the epidural space, and they are often associated with a dilated epidural venous pouch. Treatment involves endovascular, open surgical, or combined approaches.

Abstract P1115: Epicardial Signaling Regulates Myocardial Contractility Via Mirna

Background: A congenital left ventricular aneurysm is a rare cardiac malformation that maycause heartfailure, ventricular wall rupture, ventricular arrythmia or sudden cardiac death. However, mechanisms of congenital left ventricular aneurysm are not known. Paracrinesignals from cardiomyocytes, such as a cardiokine, prokineticin-2, can activate EPDCsdifferentiation in adult heart to promote neovascularization. How the reciprocal interaction viaprokineticin and miRs from epicardium to cardiomyocytes affect heart growth and function,and how EMT-related events contributecardiomyocyte proliferation and function areunknown. MicroRNA (miR124) has an important role in the adult heart, however, its role incardiac development is unknown. Results: Here in this study, by deletion of a prokineticin-2 receptor PKR1 through epicardialcell linage tracing at the different developmental stages of mice embryos, we found that thesemice exhibited ventricular rupture and embryonic lethality. Indeed, miR-124 was significantlyupregulated in PKR1 -deficient epicardial cells both in vitro and in vivo , whereas ectopicexpression of these miRs in epicardial cells resulted in the reduced expression of SNAI2 andsubsequently led to impaired EMT and EMT-related events such impaired migration andincreased apoptosis. Wild type mice cardiomyocytes that were cultured in condition mediumderived from PKR1-deficient epicardial cells had a lower beating rate and contractility. Treatment of the cardiomyocytes with miR-124mimic exhibited the same phenotype, that wasrestored by miR-124 inhibitor, indicating involvement of mir124 in epicardium-cardiomyocyte communication and regulation of cardiomyocyte contractility. Conclusion: These finding reveals a key signaling pathway in which a cardiokine,prokineticin-2 promotes EMT to form EPDCs and their migration in an autocrine manner, andsupports myocardial growth and contractility through repressing miR124. Our study mayprovide novel insight in etiology of congenital defects and new strategies to promotemyocardial regeneration.

Surgical Treatment of Cerebral cavernous Malformations: Report of 6 Cases and pertinent Literature review

Cerebral cavernous Malformation (CCM) is a rare neurovascular malformation accounting 0.5% to 4% of all intracranial vascular malformations. People harboring CCM may be symptomatic or may present with seizure, hemorrhage or progressive neurological deficit. Asymptomatic CCM needs no treatment. The symptomatic CCM may or may not require intervention. The best treatment for symptomatic CCM is microsurgical excision. Over a period of five years we have been managing I2 patients with CCM, and out of them 6 patients who were symptomatic required microsurgical excision. Here, we discuss these 6 surgically managed patients and appropriate literature related to CCMs would be reviewed.

Odontoma and other congenital dental anomalies: Implications for forensic identification.

Forensic odontology plays a crucial role in establishing the identity in mass disasters and criminal cases with high accuracy. Dental anomalies and features help in such situations. Congenital and developmental dental anomalies can be easily documented to establish distinctive and individualistic characteristics of an individual. The location, number of teeth involved, and the type of anomaly vary between individuals. Similarly, dental malformations also assist greatly in the identification process. Many types of dental anomalies have been studied in the past for their individualistic characteristics in forensic examinations. One such dental anomaly is odontoma, which is a benign odontogenic malformation. This malformation may also help in the identification of the deceased, when recorded and examined accurately. An odontome is a malformed teeth-like structures consisting of enamel, dentin, and pulpal tissue, formed due to the growth of completely differentiated epithelial and mesenchymal cells. If antemortem (AM) dental records incorporate information regarding odontomes and other dental anomalies, including in radiographs, orthopantomograms or microradiographs, positive identification may be established by comparison of these records with postmortem (PM) records. In the present communication, a rare case of compound composite odontoma in the anterior mandible with multiple denticles has been discussed with a brief overview of congenital and developmental dental anomalies. The authors emphasize the importance of such rare dental anomalies and malformations which may be used for identifying the deceased in mass disasters and forensic identification.

Idiopathic enlargement of the right atrium masking left atrial aneurysm in a neonate.

An idiopathic enlargement of the right atrium is an extremely rare cardiac malformation. There are no established guidelines for the management of this disease, especially concerning medical versus surgical therapeutic approach and the timing for an operation. We report in this case about a neonate that first was treated conservatively until the age of 5 month and finally got an operative resection of the aneurysm. After surgery, unexpected complications occurred. A second aneurysm in the left atrium was demasked. Furthermore, a progressive dilatation of both atrial chambers after resection required regular follow-up and ongoing evaluation of treatment.

“Leopard skin” sign: Magnetic resonance imaging appearance of Lhermitte-Duclos disease with histopathologic correlation

Dysplastic cerebellar gangliocytoma or Lhermitte-Duclos disease (LDD) is a rare hamartomatous malformation of cerebellum that can occur in isolation or as a component of Cowden syndrome. Although uncommon, the characteristic clinical symptoms and magnetic resonance imaging (MRI) features are highly suggestive of the condition and histopathological features confirm the diagnosis. We report a case of LDD, presenting with “Leopard skin” appearance of the lesion on MRI with a brief review of imaging, clinical, and histopathological features.

Vein of Galen aneurysmal malformation in newborns: a retrospective study to describe a paradigm of treatment and identify risk factors of adverse outcome in a referral center.

Vein of Galen aneurysmal malformation (VGAM) is a rare cerebral vascular malformation associated with significant morbidity and mortality. Newborns with VGAM without adequate treatment may develop rapidly deteriorating high output heart failure (HOHF) and are at risk for severe neurological outcomes. To describe the clinical course and management of newborns with VGAM, and identify which echocardiographic and neuroradiologic factors may be associated with severe heart failure at birth and adverse short term outcomes. This is a single center retrospective cohort study including all consecutive newborns with VGAM admitted to Gaslini Children's Hospital between 2009 and 2022. We reviewed clinical data, intensive care support, fetal and neonatal cardiologic and neuroradiologic findings and we studied the association with severe HOHF, endovascular complications and death. Out of 40 newborns, 17 (42.5%) developed severe HOHF requiring early endovascular procedures. Medical treatment was focused on the main components of HOHF by providing inotropic support and peripheral vasodilation. Pulmonary vasodilators were avoided to reduce the negative effects of pulmonary overflow and prevent vascular remodeling. Reduction of the obligatory left to right shunt through the VGAM was possible only through endovascular treatment. Fetal cardiothoracic ratio was significantly associated with severe HOHF at birth and death. Cardiologic parameters of right ventricular overload, pulmonary hypertension and systemic steal were the leading findings associated with haemodynamic compromise at birth. The mediolateral diameter of the straight or falcine sinus at its shortest section (SS-MD), and arterial pseudofeeders were significantly associated with severe HOHF at birth in prenatal and postnatal assessments. None of the postnatal echocardiographic and MRI variables, nor a higher inotropic support were associated with major periprocedural complications or death. Mortality was due to palliation for congenital severe brain damage (4/40, 10%), or major periprocedural complications (3/40, 7.5%). None of the patients died due to HOHF and multiorgan failure. Overall survival at discharge was 82.5% (33/40). The complexity of neonatal VGAM pathophysiology requires a multidisciplinary approach, specialized intensive care management, and early endovascular treatment to reduce mortality and optimize clinical outcomes. Cardiologic and neuroradiologic parameters are key to define risk stratification and treatment strategies.

Intrahepatic portosystemic shunts, from prenatal diagnosis to postnatal outcome: a retrospective study

ObjectiveCongenital intrahepatic portosystemic shunts (IHPSS) are rare vascular malformations resulting in blood bypassing the liver to the systemic circulation. Previous studies included symptomatic patients diagnosed postnatally, but the outcome of...

Congenital Cystic Adenomatoid Malformation: A Case Report

The case report is being done to increase the knowledge of Congenital Cystic Adenomatoid Malformation (CCAM) along with to better understand about the disease and its management & raise awareness. A female infant (aged 9 months and birth weight 2500 gm) was selected as participant. After physical examination, the state of the participant was good (fever:37.6ºC, heart rate: 120/min, respiratory rate: 40/min). Holding a good health certificate, a cystic image was identified at pulmonary artery in chest X-ray report. The histology findings were consistent with CPAM Type I. CPAM surgery, generally favorable, results in low postoperative morbidity and mortality. CPAM is a rare developmental malformation of lung that causes pulmonary compression and hypoplasia leading to respiratory distress but the postnatal management of asymptomatic CPAM remains controversial.

Consensus recommendations on the evaluation and treatment of congenital laryngeal clefts

Congenital laryngeal cleft is a rare airway malformation, mainly manifested as choking, feeding difficulties, which affects the growth and development of children. Patients with a severe laryngeal cleft may have recurrent aspiration, leading to cyanotic spells, or even death. Advances in development of endoscopic techniques have made early diagnosis possible. Depending on the degree of cleft, management may involve a variety of approaches ranging from medical management alone to open repair. Therefore, it is important for pediatric ENT doctors to diagnose and evaluate in clinical practice. This consensus statement, developed by the Pediatric otorhinolaryngology Professional Committee of the Pediatrician Branch of the Chinese Medical Doctor Association, provides comprehensive recommendations and standardized guidance on diagnosis and management of laryngeal cleft, based on symptomatology, physical examinations, and laboratory tests.

Anesthetic challenges in a child with congenital pulmonary airway malformation for right lower lobectomy

Abstract Congenital pulmonary airway malformation is a rare benign airway malformation, affecting the trachea, bronchi, bronchiolar, or alveolar systems with cystic and adenomatous lesions. This sequestered part of the lung becomes nonfunctioning and causes recurrent pulmonary infections. The definitive treatment is surgical resection of the diseased segments by thoracotomy requiring general anesthesia and controlled ventilation. The anesthetic challenges in pediatric lung surgeries are airway management, the requirement of one-lung ventilation, and maintaining saturation. The lung separation maneuvers in pediatric patients are difficult due to the nonavailability of appropriate size double-lumen endotracheal tube (ETT) or one-lung ventilation with bronchial blockers. We present how we managed to provide general anesthesia and controlled ventilation using single-lumen ETT to provide a good operating condition for right lower lobectomy.