Sudden death due to Takayasu arteritis complication associated with situs inversus totalis: A case discovered at autopsy.

Takayasu arteritis is a rare pathology that usually has general and atypical signs that make its diagnosis difficult. These characteristics can delay diagnosis, thus leading to complications and death. We, herein, report an autopsy case of a 25-year-old female patient with a history of multiple consultations for dyspnea. During these consultations, no diagnosis was made. She was found unconscious near her home and shortly after, she was declared dead. Forensic autopsy revealed superficial traumatic lesions. Internal examination revealed complete situs inversus. Multiple bilateral pleural adhesions and bilateral moderate effusion were found. The heart was heavy with thickening of the aortic wall (1.1cm), carotid arteries, and pulmonary trunk, associated with a large aortic valve and evidence of leakage. Histological examination of the aorta and its major branches showed features of panarteritis with segmental involvement. The vascular wall was thick with lymphoplasmacytic infiltrate and giant cells involving mainly the medio-adventitial junction. Disruption of the elastic lamina and reactive fibrosis in the intima were also noted. Diagnosis of large vessel vasculitis and particularly Takayasu arteritis was made. Death was therefore attributed to heart failure due to aortic insufficiency as a complication of Takayasu arteritis.

Infrarenal abdominal aortic aneurysm in a patient with situs inversus totalisand its therapeutic implications / Aneurisma de aorta abdominal infrarrenal en paciente con situs inversus totalisy sus implicaciones terapéuticas

Background: situs inversus totalis (SIT) is a congenital pathology where the organs acquire a disposition contraryto the usual, “mirror image”.Case report: we present a 58-year-old man with known SIT, followed-up by the vascular surgery service for aninfrarenal abdominal aortic aneurysm (AAA) with a transverse diameter of 42 mm with growth to 56 mm, repairedby transabdominal approach, and with satisfying results.Discussion: the coexistence of SIT and AAA is extremely rare, its prevalence being unknown. This publicationdiscusses the possible therapeutic implications of AAA in this situation.(AU)

Introducción: el situs inversus totalis (SIT) es una patología congénita en la que los órganos adquieren una dispo-sición contraria a la habitual: “imagen en espejo”.Caso clínico: presentamos a un varón de 58 años con conocido SIT en seguimiento por el servicio de cirugía vas-cular por un aneurisma de la aorta abdominal (AAA) infrarrenal de 42 mm de diámetro transverso con crecimientohasta los 56 mm, reparado mediante abordaje transabdominal y con resultado final satisfactorio.Discusión: la coexistencia de SIT y AAA es extremadamente rara y su prevalencia se desconoce. La presente publi-cación trata las posibles implicaciones terapéuticas de los AAA en tal situación.(AU)

The second DDOST-CDG patient with lactose intolerance, developmental delay, and situs inversus totalis.

Congenital disorders of glycosylation (CDGs) are inherited metabolic diseases affecting protein and lipid glycosylation. DDOST-CDG is a rare, newly identified type of CDGs, with only one case reported so far. In this study, we report a Chinese patient with a homozygous pathogenic variant in DDOST (c.1187G>A) and who presented with feeding difficulty, lactose intolerance, facial dysmorphism, failure to thrive, strabismus, high myopia, astigmatism, hypotonia, developmental delay and situs inversus totalis. Serum transferrin isoelectrofocusing demonstrated defective glycosylation in our patient. This finding further identifies DDOST as a genetic cause of CDGs and expands the clinical phenotype of DDOST-CDG.

Choledochal cyst and aberrant biliary configuration along with situs inversus totalis: a case report.

Situs inversus totalis is the complete transpositioning of thoracoabdominal viscera into a mirror image of the normal configuration. Choledochal cyst is the congenital cystic dilation of the biliary tract. Both these conditions coexisting in a patient is extremely rare. We hereby present a case of type IC choledochal cyst in a patient with situs inversus totalis presenting with biliary sepsis secondary to choledocholithiasis. Also detailed are the management and operative strategies employed to deal with this rare entity.

Double rarity: malignant masquerade biliary stricture in a situs inversus totalis patient.

BACKGROUND: Situs inversus totalis is a rare anatomical variation of both the thoracic and the abdominal organs. Common bile duct strictures can be caused by malignant and benign diseases as well. 7-18% of the latter ones are 'malignant masquerade' cases, as pre-operative differentiation is difficult. CASE PRESENTATION: We present the case of a 68y male patient with known situs inversus totalis and a recent onset of obstructive jaundice caused by a malignant behaving common bile duct stricture. Technically difficult endoscopic retrograde cholangiopancreatography, brush cytology, magnetic resonance cholangiopancreatography, endoscopic ultrasound, and percutaneous transhepatic drainage with stent implantation were performed for proper diagnosis. Cholecystectomy, common bile duct resection with hilar lymphadenectomy, and hepatico-jejunostomy have been performed following multidisciplinary consultation. The final histology report did not confirm any clear malignancy, the patient is doing well. CONCLUSION: In situs inversus patients, both diagnostic and therapeutic procedures can lead to various difficulties. Benign biliary strictures are frequently misdiagnosed preoperatively as cholangiocellular carcinoma. Surgery is usually unavoidable, involving a significant risk of complications. The co-existence of these two difficult diagnostic and therapeutic features made our case challenging.

A Huge Ovarian Mucinous Cystadenoma in a 15-Year-Old Girl with Situs Inversus Totalis: Report of a Rare Case.

BACKGROUND: Ovarian mucinous cystadenomas with situs inversus totalis are infrequent in pubertal girls. Surgical techniques on their treatment without affecting ovary anatomical and physiological function have always been a great challenge. CASE: A 15-year-old girl presented with abdominal distension and pain due to some huge growths. Computed tomography imaging showed that the heart and whole abdomen viscera were inversely located. Two big low-density masses were found in the abdominopelvic cavity. An exploratory laparotomy was performed and 2 tumors were removed. Pathology confirmed a mucinous cystadenoma. SUMMARY AND CONCLUSION: Ovarian mucinous cystadenomas with situs inversus totalis can be detected with detailed physical and radiological examination. For adolescent female patients, particular attention should be paid to protect the reproductive anatomical structure during surgery.

CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module.

Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.

Short foveo-disc distance in situs inversus of optic disc.

Situs inversus of optic disc (SIOD) is thought to be a congenital optic disc abnormality that is caused by dysversion of optic nerve insertion. SIOD, however, has many additional features that cannot be explained by abnormal optic-nerve-insertion directionality. In this study, we measured the distance between the fovea and disc in 22 eyes of 15 SIOD patients. For comparison, two control eyes were matched with each SIOD eye by age and axial length. The vertical distance between the temporal vascular arcades also was measured. The foveo-disc distance was shorter in the SIOD eyes than in the control eyes, while the inter-arcade distance did not differ. Further, we measured the circumpapillary retinal nerve fiber layer thickness, which showed nasal crowding of two humps in the SIOD eyes. This nasal crowding disappeared when we shifted the circle scan by the mean difference (465 µm) of the foveal-disc distance between the two groups. Our findings suggest that the optic disc was located closer to the fovea than it would have been normally. Thus, SIOD might reflect incomplete expansion of the posterior pole in the direction of the fovea-disc axis.

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.

A detailed pathway and termination of thoracic duct in a Japanese female cadaver with situs inversus totalis.

Although the thoracic duct (TD) requires special attention during thoracic surgery, to our knowledge, its detailed course in the situs inversus totalis (SIT) case has not been reported. We encountered an 86-year-old Japanese female cadaver with SIT during a student anatomical practice and examine the TD. The TD originated from the cisterna chyli at the level of the 2nd lumbar vertebra, ascended along with the left side of aorta and then passed behind the aortic arch on the right side of the esophagus. The TD turned right at the first thoracic vertebra and finally emptied into the basal portion of the right external jugular vein without branching. The present running pathway of the TD was approximately in the inverted position of the normal, but its connection site to the vein and manner was very rare and has not been reported to date. Therefore, this junctional anomaly may occur during the developmental period in SIT. Further anatomical and embryological studies are required, but this report provides useful morphogenetic information of the TD and lymphovenous junction in SIT.

Idiopathic thrombocytopenic purpura in a patient with situs inversus totalis: case report and literature review.

Situs inversus totalis is a rare recessive autosomal congenital abnormality in which the mediastinal and abdominal organs are in a mirrored position when compared to the usual topography. The literature reports some cases of situs inversus totalis and concomitant conditions: spinal abnormalities, cardiac malformations and hematological diseases, such as idiopathic thrombocytopenic purpura, which is an autoimmune disease that causes thrombocytopenia due to platelet destruction or suppression of its production. This article aimed to report the coexistence of situs inversus totalis and idiopathic thrombocytopenic purpura.

SPEF2- and HYDIN-Mutant Cilia Lack the Central Pair-associated Protein SPEF2, Aiding Primary Ciliary Dyskinesia Diagnostics.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous chronic destructive airway disease. PCD is traditionally diagnosed by nasal nitric oxide measurement, analysis of ciliary beating, transmission electron microscopy (TEM), and/or genetic testing. In most genetic PCD variants, laterality defects can occur. However, it is difficult to establish a diagnosis in individuals with PCD and central pair (CP) defects, and alternative strategies are required because of very subtle ciliary beating abnormalities, a normal ciliary ultrastructure, and normal situs composition. Mutations in HYDIN are known to cause CP defects, but the genetic analysis of HYDIN variants is confounded by the pseudogene HYDIN2, which is almost identical in terms of intron/exon structure. We have previously shown that several types of PCD can be diagnosed via immunofluorescence (IF) microscopy analyses. Here, using IF microscopy, we demonstrated that in individuals with PCD and CP defects, the CP-associated protein SPEF2 is absent in HYDIN-mutant cells, revealing its dependence on functional HYDIN. Next, we performed IF analyses of SPEF2 in respiratory cells from 189 individuals with suspected PCD and situs solitus. Forty-one of the 189 individuals had undetectable SPEF2 and were subjected to a genetic analysis, which revealed one novel loss-of-function mutation in SPEF2 and three reported and 13 novel HYDIN mutations in 15 individuals. The remaining 25 individuals are good candidates for new, as-yet uncharacterized PCD variants that affect the CP apparatus. SPEF2 mutations have been associated with male infertility but have not previously been identified to cause PCD. We identified a mutation of SPEF2 that is causative for PCD with a CP defect. We conclude that SPEF2 IF analyses can facilitate the detection of CP defects and evaluation of the pathogenicity of HYDIN variants, thus aiding the molecular diagnosis of CP defects.

Idiopathic thrombocytopenic purpura in a patient with situs inversus totalis: case report and literature review / Púrpura trombocitopênica idiopática em paciente com situs inversus totalis: relato de caso e revisão da literatura

ABSTRACT Situs inversus totalis is a rare recessive autosomal congenital abnormality in which the mediastinal and abdominal organs are in a mirrored position when compared to the usual topography. The literature reports some cases of situs inversus totalis and concomitant conditions: spinal abnormalities, cardiac malformations and hematological diseases, such as idiopathic thrombocytopenic purpura, which is an autoimmune disease that causes thrombocytopenia due to platelet destruction or suppression of its production. This article aimed to report the coexistence of situs inversus totalis and idiopathic thrombocytopenic purpura.

RESUMO Situs inversus totalis é uma anormalidade congênita autossômica recessiva rara em que os órgãos mediastinais e abdominais encontram-se em posição espelhada em relação à topografia habitual. A literatura relata alguns casos de concomitância do situs inversus totalis com outras condições: anomalias espinhais, malformações cardíacas e doenças hematológicas, como púrpura trombocitopênica idiopática, que é uma doença autoimune com plaquetopenia, devido à destruição dos trombócitos ou supressão da sua produção. Esse artigo teve o objetivo de relatar coexistência de situs inversus totalis e púrpura trombocitopênica idiopática.

Dextrocardia and situs inversus totalis in a Turkish subject: a case report / Dextrocardia y situs inversus totalis en un sujeto turco: reporte de un caso

Dextrocardia with situs inversus is an uncommon anomaly affecting about 1 to 2 per 10,000 in the general population. This report describes an adult male patient with dextrocardia and in a Turkish subject. The photographic illustrations revealed transposition of some of the visceral organs such as the spleen was located right and the liver and gall bladder on the left. The heart was flattened and flipped to the right. Many people with situs inversus totalis are unaware of their unusual anatomy until they seek medical attention for an unrelated condition. So, early detection may lead to a successful surgical management and consequently offer a safer chance of survival. This report showed that dextrocardia and situs inversus can be seen amongst Turkish subjects.

La dextrocardia con situs inversus es una anomalía poco frecuente que afecta aproximadamente de 1 a 2 personas por 10.000 en la población general. Este informe describe un paciente masculino adulto con dextrocardia. Las figuras revelaron que la transposición de algunos de los órganos viscerales, como el bazo, se ubicada a la derecha y el hígado y la vesícula biliar a la izquierda. El corazón fue aplastado y girado hacia la derecha. Muchas personas con situs inversus totalis desconocen su anatomía inusual hasta que buscan atención médica por una afección no relacionada. Por lo tanto, la detección temprana puede llevar a un manejo quirúrgico exitoso y, en consecuencia, ofrecer una posibilidad más segura de supervivencia. Este informe mostró que la dextrocardia y el situs inversus se pueden encontrar entre los sujetos turcos.

Characterization of CCDC103 expression profiles: further insights in primary ciliary dyskinesia and in human reproduction.

PROPOSE: To study CCDC103 expression profiles and understand how pathogenic variants in CCDC103 affect its expression profile at mRNA and protein level. METHODS: To increase the knowledge about the CCDC103, we attempted genotype-phenotype correlations in two patients carrying novel homozygous (missense and frameshift) CCDC103 variants. Whole-exome sequencing, quantitative PCR, Western blot, electron microscopy, immunohistochemistry, immunocytochemistry, and immunogold labelling were performed to characterize CCDC103 expression profiles in reproductive and somatic cells. RESULTS: Our data demonstrate that pathogenic variants in CCDC103 gene negatively affect gene and protein expression in both patients who presented absence of DA on their axonemes. Further, we firstly report that CCDC103 is expressed at different levels in reproductive tissues and somatic cells and described that CCDC103 protein forms oligomers with tissue-specific sizes, which suggests that CCDC103 possibly undergoes post-translational modifications. Moreover, we reported that CCDC103 was restricted to the midpiece of sperm and is present at the cytoplasm of the other cells. CONCLUSIONS: Overall, our data support the CCDC103 involvement in PCD and suggest that CCDC103 may have different assemblies and roles in cilia and sperm flagella biology that are still unexplored.

Whole-exome sequencing identifies a novel CCDC151 mutation, c.325G>T (p.E109X), in a patient with primary ciliary dyskinesia and situs inversus.

We identified a novel CCDC151 mutation, c.325G>T (p.E109X), in a patient with primary ciliary dyskinesia and situs inversus. This stopgain mutation was predicted to be disease causing by bioinformatics program (MutationTaster) and was also not presented in the current Genome Aggregation Database (gnomAD), Exome Aggregation Consortium (ExAC), Single Nucleotide Polymorphism Database (dbSNP), or National Heart, Lung, and Blood Institute (NHLBI) and Exome Sequencing Project (ESP). In addition, to the best of our knowledge, the present study was the first to report a CCDC151 mutation in primary ciliary dyskinesia patients with situs inversus in mainland China. In conclusion, our finding expands the spectrum of CCDC151 mutations, and more importantly our study provides additional support that CCDC151 plays important roles in left-right patterning and ciliary function.

Casuística. Vesícula biliar siniestra (sinistraposición): Caso clínico / Left-sided Gallbladder (Sinistraposition of the gallbladder)

A rare case of left-sided gallbladder (sinistraposition) is reported with review of the literature. Left-sided gallbladder is very unusual, with a frequency of 0.3% of the cases, being generally associated to situs inversus. The aim of this invesigation was to establish the association between left-sided gallbladder and right-sided round ligaments. Left-sided gallbladder is a rare anomaly and has been classified into two situations: 1) gallbladder migration to the left side, and 2) development of a second gallbladder with atrophy of the original one. Left-sided gallbladder were reported to be associated with right-sided round ligaments.

Novel deletion mutation in the glucokinase gene from a korean man with GCK-MODY phenotype and situs inversus.

A novel mutation in intron 9-exon 10 boundary of the GCK gene was detected in a male patient with clinical features of GCK-MODY and situs inversus. This case highlights the value of sequencing the GCK gene in individuals with GCK-MODY phenotype and no family history of monogenic diabetes.