Genetic Spectrum and Clinical Characteristics of Patients with Primary Ciliary Dyskinesia: a Belgian Single Center Study.

PURPOSE: We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD). METHODS: We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes. RESULTS: We enrolled 74 patients with a median age of 25.58 years. The most frequently involved genes were DNAH11 (n = 23) and DNAH5 (n = 19). The most frequent types of pathogenic variants were missense (n = 42) and frameshift variants (n = 36) and most patients had compound heterozygous variants (n = 44). Ciliary ultrastructure (p < 0.001), situs (p = 0.015) and age at diagnosis (median 9.50 vs 4.71 years, p = 0.037) differed between DNAH11 and DNAH5. When correcting for situs this difference in age at diagnosis was no longer significant (p = 0.973). Patients with situs inversus were diagnosed earlier (p = 0.031). Respiratory tract microbiology (p = 0.161), lung function (cross-sectional, p = 0.829 and longitudinal, p = 0.329) and chest CT abnormalities (p = 0.202) were not significantly different between DNAH11 and DNAH5 variants. CONCLUSION: This study suggests a genotype-phenotype correlation for some of the evaluated clinical characteristics of the two most frequently involved genes in this study, namely DNAH11 and DNAH5.

Clinical Presentation and Therapy of Anomalies of the Situs.

Situs abnormalities may occur in many and most often more complex congenital cardiac malformations. These conditions are collectively referred to as heterotaxy syndromes, derived from the Greek words "heteros" meaning different and "taxos" meaning orientation or arrangement. Clinically, heterotaxy spectrum encompasses defects in the left-right laterality and arrangement of visceral organs. "Situs" is derived from Latin and is the place where something exists or originates. In human anatomy, situs can be solitus (derived from Latin, meaning "normal"), inversus, or ambiguus. Heterotaxy syndrome represents an intermediate arrangement of internal organs between situs solitus and situs inversus, also known as "situs ambiguous." Situs ambiguus describes an abnormal distribution of major visceral organs within the chest and abdomen. The determination of situs as normal, inversus, or ambiguus is primarily based on the location of unpaired organs such as the spleen, liver, stomach, and intestines. Diagnosis is made by clinical examination, echocardiography, a chest X-ray (position of the heart, stomach, and liver), and ultrasound of the abdominal organs. Situs is considered solitus if the left atrium, spleen, stomach, and the trilobed lung are on the left side and the liver and bilobed lung are on the right side. Situs ambiguus is present if the location of unpaired structures is random or indeterminate even after detailed and appropriate imaging. Situs inversus results when the arrangement of the thoracic and abdominal organs is mirrored. Individuals with situs inversus or situs solitus do not experience fatal dysfunction of their organ systems, as general anatomy and morphology of the abdominothoracic organ-vessel systems are conserved.

Radiofrequency ablation of persistent atrial fibrillation in a patient with situs inversus totalis and interrupted inferior vena cava.

INTRODUCTION: Catheter ablation of atrial fibrillation (AF) has emerged as the most effective therapy. However, rare anatomical abnormalities such as situs inversus totalis, dextrocardia, or interrupted inferior vena cava can make ablation challenging. METHODS AND RESULTS: We report a case of a 55-year-old woman with situs inversus totalis, dextrocardia, surgical atrial septal defect repair, left-sided dual chamber pacemaker in place, and symptomatic recurrent persistent AF who underwent successful pulmonary vein and posterior wall isolation by the superior access from the left internal jugular vein. CONCLUSIONS: It is a feasible and safe approach with support of transesophageal echocardiography and multiple emerging technologies.

Robotic magnetic navigation-guided pulmonary vein isolation in an atrial fibrillation patient with dextrocardia situs inversus: techniques and potential advantages.

BACKGROUND: Dextrocardia with situs inversus (DSI) is a very rare congenital anomaly. Catheter manipulation and ablation of atrial fibrillation (AF) in patients with this anatomical variant is challenging for the operators. This case report presents a safe and effective AF ablation guided by the robotic magnetic navigation (RMN) system in combination with intracardiac echocardiograhy (ICE) in a patient with DSI. CASE PRESENTATION: A 64-year-old male with DSI was referred for catheter ablation of symptomatic, drug-refractory paroxysmal AF. One transseptal access was achieved via the left femoral vein under the guidance of ICE. The three-dimensional reconstruction of the left atrium and the pulmonary veins (PVs) were performed by the magnetic catheter using the CARTO and the RMN system. Then, the electroanatomic map and pre-acquired CT images were merged. Finally, bilateral circumferential ablation lines were delivered around the ipsilateral PV ostia to achieve complete PV isolation (PVI). CONCLUSIONS: This case demonstrates that AF catheter ablation under the guidance of the RMN system using ICE is feasible and safe in a patient with DSI. Moreover, the combination of these technologies broadly facilitates treatment of patients with complex anatomy, while reducing the risk of complications.

Situs inversus totalis with local metastasis of gallbladder carcinoma and variation of the common hepatic artery.

BACKGROUND: Situs inversus totalis (SIT) is a rare congenital anomaly characterized by a complete transposition of all the viscera. SIT cases were usually reported because of the presence of tumors, leading to false association between them. Therefore, any research that advances our understanding on SIT is highly required. This study firstly describes a very rare case of SIT with "jumping" metastasis to pancreas of gallbladder carcinoma. CASE PRESENTATION: A 69-year-old female patient presented at our hospital with complaints of one month of epigastric pain was studied. She had not sought for treatment prior the visit. Imaging examinations of this patient revealed SIT and a variation of the common hepatic artery with concomitant tumors of gallbladder and pancreas. However, there was no evidence of distant metastases beyond the abdominal cavity. She underwent a combination of radical cholecystectomy, total pancreatectomy, splenectomy and hepatic artery-splenic artery reconstruction. Histological analyses revealed metastasis of the gallbladder carcinoma in to the pancreas. Although the patient opted against chemotherapy, she survived without tumor for 16 months following the surgery. A review of the current literature on association with SIT and tumor occurrence was presented. CONCLUSIONS: It is a great surgical challenge for the resection of multicenter hepatobiliary and pancreatic tumors in such rare SIT anatomical abnormalities with vascular variants. A reliable surgical plan based on detailed preoperative imaging and intraoperative anatomical exploration is crucial to achieving radical resection.

Successful management of ectopic kidney stones in a patient with situs inversus totalis: a rare case report.

BACKGROUND: Situs inversus totalis is a very rare congenital anatomical variation, in which all thoracic and abdominal organs are right-left inverted. This condition is associated with an increased risk of organ malformations including ectopic kidney, which is a very rare combination. CASE PRESENTATION: A 56-year-old male presented with colicky left iliac pain associated with nausea, vomiting, and irritative lower urinary symptoms. The patient has a medical history of recurrent lower urinary infections and a family history of situs inversus totalis. Radiological images demonstrated dextrocardia, situs inversus totalis of all the abdominal organs, and an ectopic pelvic kidney on the left side, with 4 stones inside it. Left nephrectomy was performed due to extensive renal damage. At discharge and during follow-up, the patient's condition was satisfactory and stable. CONCLUSIONS: The ectopic kidney may present diagnostic and therapeutic challenges when associated with situs inversus.

ERCP and situs inversus.

An 85-year-old female with situs inversus totalis was admitted due to obstructive jaundice, secondary to multiple choledocholithiasis and distal biliary stenosis due to adenocarcinoma of the head of the pancreas, with duodenal infiltration and metastatic liver disease. An endoscopic retrograde cholangiopancreatography (ERCP) was attempted in the supine position but bile duct cannulation was not possible due to duodenal infiltration. Finally, a palliative biliary stent was placed percutaneously, with resolution of the jaundice.

[Stanford Type A Aortic Dissection with Tricuspid Regurgitation in a Patient with Situs Inversus Totalis].

Situs inversus totalis is a congenital anomaly characterized by a mirror image transposition of the normal visceral organs, which makes it difficult to perform aortic surgery accurately. Stanford type A aortic dissection in patients with this condition is very rare and difficult to assess and manage. We report a case of Stanford type A aortic dissection with situs inversus totalis. The patient presented with severe tricuspid regurgitation with annulus enlargement due to chronic atrial fibrillation, requiring ascending aortic replacement and tricuspid annuloplasty. These procedures were performed after the operator swapped the left and right positions during the operation. Postoperative course was uneventful. By carefully checking the preoperative computed tomography images and changing the operator's position during the operation, it is possible to safely perform Stanford type A aortic dissection surgery in patients with situs inversus totalis.

Aortic valve replacement for dextrocardia with situs inversus totalis.

Dextrocardia is a rare congenital cardiac positional anomaly. A 74-year-old woman was referred for aortic regurgitation (AR). Chest X-ray revealed a mildly enlarged heart that directed to the right side. Transthoracic echocardiography showed AR due to cusp prolapse with a dilated left ventricle and reduced wall motion. Computed tomography demonstrated the heart and great vessels in a mirror image of their normal positions. A median sternotomy performed by the surgeon standing on the right side of the patient. After establishing a cardiopulmonary bypass, the surgeon moved to the left side of the patient, and then performed aortic valve replacement.

Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia: a case report.

BACKGROUND: Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies. CASE PRESENTATION: Here, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified. CONCLUSIONS: We identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed.

Dextrocardia, situs solitus, inlet ventricular septal defect (VSD), and iatrogenic tricuspid regurgitation (TR)-A surgical perspective.

Dextrocardia with situs solitus is a rare congenital anomaly, often associated with intra- or extracardiac malformations. A clear understanding of the spatial orientation of the chambers of the heart for planning surgical approach, is imperative. Access to the right side of the heart, especially for repair of the tricuspid valve can be challenging. We describe a case of dextrocardia, situs solitus, inlet ventricular septal defect (VSD) with iatrogenic tricuspid regurgitation (TR) in an adult patient, highlighting the surgical aspects essential for a successful outcome.

Transseptal Approach for Mitral Valve Replacement in Dextrocardia with Situs Inversus Totalis: A Case Report and Review of the Literature.

We consider mitral valve disease requiring surgery in a patient with dextrocardia and situs inversus totalis to be an exceptional finding. The transseptal approach for mitral valve surgery in dextrocardia represents a technical challenge owing to its anatomic particulars. We present the case of a 56-year-old female patient who had been diagnosed with situs inversus totalis in childhood and with chronic atrial fibrillation in adulthood and was under oral anticoagulant treatment. She was referred to our hospital for increasing dyspnea and palpitation. Transthoracic echocardiography detected severe mitral regurgitation associated with moderate tricuspid regurgitation, with normal left and right ventricular function. Contrast chest computed tomography (CT) and preoperative abdominal CT showed both dextrocardia and situs inversus totalis, with normal continuity of the inferior vena cava. Biatrial cannulation was performed with the surgeon standing on the right side of the patient, and mitral valve replacement using a transseptal approach was performed with the surgeon standing on the left side of the patient. In this case report, we emphasize the rarity of mitral valve disease in a patient with dextrocardia and the inherent potential difficulty that can appear in this particular anatomic condition.

Stress cardiomyopathy in dextrocardia with situs inversus and anomalous coronary arteries.

We present a 53-year-old male with the rare constellation of stress cardiomyopathy, dextrocardia with situs inversus and anomalous coronary anatomy. This case highlights the difficulties faced when managing patients with uncommon disorders and demonstrates a rare overlap of acquired and CHD.

Ductus arteriosus location in relation to aortic arch position, branching pattern, and viscero-atrial situs.

AIM: To investigate ductus arteriosus (DA) location in relation to viscero-atrial situs and branching pattern of the right aortic arch (RAA). MATERIALS AND METHODS: Computed tomography (CT) images of paediatric patients (May 2015 to July 2017, n=352) referred for evaluation of cardiovascular malformations were reviewed retrospectively. Patients with RAA were identified and images were analysed for documentation of the viscero-atrial situs, the branching pattern, DA location, and associated malformations. RESULTS: The study included 64 RAA patients, 45 situs solitus, 11 situs ambiguous, and eight situs inversus. Mirror-image branching was observed in 34 situs solitus, 11 situs ambiguous, and seven situs inversus patients. Aberrant left subclavian artery (ALSCA) was present in 10 situs solitus and one situs inversus patient. One patient with situs solitus had isolated left subclavian artery. The location of the DA was identifiable in 32 patients (19 left and 13 right). In situs solitus with mirror-image branching, the DA was left in 10, right in four patients. In situs inversus and ambiguous with mirror-image branching, the DA was right in eight and left in two patients. In patients with ALSCA, the DA was left in seven and right in one patient. The location of the DA was identifiable in 85 patients with left aortic arch (left-sided in 84, right-sided in only one patient). CONCLUSION: The location of DA in RAA varies according to viscero-atrial situs and branching pattern. In mirror-image branching, the DA is more commonly left-sided with situs solitus and more right-sided with abnormal viscero-atrial situs.

There are more anatomical variants in heaven and earth, Horatio, than are dreamt of in our philosophy: the precaval left renal artery.

AIM: To describe the CT findings in eight patients with left-sided inferior vena cava (IVC) in whom the left renal artery presented a precaval course (pLRA). MATERIALS AND METHODS: We searched the teaching files of six radiology departments for patients with pLRAs. Eight patients were found, and the available imaging studies and clinical histories were reviewed. Associated vascular and renal anomalies were noted. RESULTS: No patient had been examined for problems related to the vascular anomaly found. Four had a double IVC and two a solitary left IVC; in all, the left-sided IVCs had hemiazygos continuation. One patient had situs viscerum inversus. In one case, there was a left kidney in left iliac fossa. CONCLUSION: Although rare and probably overlooked, a pLRAs can be encountered in patients with situs viscerum inversus or presenting a left-sided IVC with hemiazygos continuation. These vessels can cause technical problems during surgery at the left renal hilum and should be specifically searched for in patients with vascular anomalies.

STEMI in a patient with mirror-image dextrocardia.

ST-segment elevation myocardial infarction (STEMI) is a potentially life-threatening diagnosis that cannot be missed on ECG interpretation. However, ECG interpretation may not be straightforward in patients with dextrocardia. This case report discusses the presentation of a patient with situs inversus with dextrocardia who was found to have an acute inferior MI, and how this anatomical change results in an atypical ECG and clinical presentation.