A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy.

BACKGROUND: Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left-right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy. CASE PRESENTATION: We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left-right body axis. CONCLUSIONS: Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.

Surgical management of hearts with isomeric atrial appendages.

BACKGROUND AND AIM: On the basis of previously published accounts, coupled with our own experience, we have assessed the surgical approaches to patients with isomeric atrial appendages. METHODS: We reviewed pertinent published studies on surgical treatment of individuals with isomeric atrial appendages, with the pertinent surgical details provided by most of the manuscripts. RESULTS: Half of patients with right isomerism, and two-thirds of those with left isomerism have bilateral superior caval veins. Azygos extension of the inferior caval vein is reported in three-quarters of those with left isomerism. The coronary sinus is universally absent in right isomerism, along with totally anomalous pulmonary venous connection, and is absent in two-fifths of those with left isomerism. Univentricular atrioventricular connections are expected in up to three-quarters of those with right isomerism. Atrioventricular septal defect is reported in up to four-fifths, more frequently in right isomerism, with such patients typically having discordant ventriculoatrial connections or double outlet right ventricle. Reported mortalities extend to 85% for those with right, and 50% for those with left isomerism. In right isomerism, mortality is up to 54% for systemic-to-pulmonary arterial shunting, up to 75% for univentricular repair, and up to 95% for repair of totally anomalous pulmonary venous connection itself. No more than one-quarter had undergone Fontan completion, with reported mortalities of 21%. CONCLUSION: Early surgical results are satisfactory in patients with left isomerism, but disappointing for those with right. Recent advances in cardiac and liver transplantation may offer improved survival.

Heterotaxy - Res ipsos loquitur.

The essence of so-called heterotaxy is the potential disharmony between the arrangement of the bronchuses, abdominal organs, and the atrial appendages. Accurate description of the heart, however, can only be provided by specific description of these features, all of which are readily discernible in the clinical setting. We argue that, when accurate description of the atrial and visceral arrangement is provided, along with appropriate description of the intracardiac findings, no further accuracy is gained by suggesting that an individual heart is "heterotaxic".

Fatal pneumococcal septicemia in a girl with visceral heterotaxy and polysplenia: a case report.

We report an unusual case of a 15-month old previously healthy girl who died of pneumococcal septicemia in the background of visceral heterotaxy with polysplenia. Heterotaxy can also present with asplenia whereas polysplenia cases usually present with functional asplenia. Of particular note, this girl received the 13-valent pneumococcal conjugate vaccine as recommended by the Centers for Disease Control and Prevention in the routine pediatric immunization schedule used in the USA and Canada. Unfortunately, although the strain causing death (serotype 22F) is not contained in Prevnar 13®, it is in the 23-valent pneumococcal polysaccharide vaccine (e.g. Pneumovax 23®), currently suggested only for immunocompromised children age 2 with either functional or anatomic asplenia. This syndrome has the potential of being diagnosed prenatally. The intent of our case report is to raise awareness of the syndrome, highlight that heterotaxy patients with polysplenia are at danger for infections with encapsulated organism, such as pneumococcus, meningococcus, and Haemophilus influenza amongst others due to functional asplenia, recommend the 23-valent pneumococcal polysaccharide vaccine for these children before age two for the outlined reasons, and illustrate that with early diagnosis of the heterotaxy syndrome, and early diagnosis and treatment of septic complications, the morbidity or death of young children with heterotaxy syndrome can likely be reduced or prevented.

The importance of being isomeric.

In the normal individual, the parietal components of the body are mirror-imaged and appropriately described as isomeric. The thoraco-abdominal organs, in contrast, are lateralized. However, in "visceral heterotaxy," the thoraco-abdominal organs also show some degree of isomerism, best seen in the arrangement of the bronchial tree. Whether isomerism can be found within the heart remains controversial. One of two recent publications in this journal emphasized the crucial features of bronchial isomerism; the other, in contrast, confused the situation of isomerism within the heart. In this review, we show how the topic of cardiac isomerism is clarified by concentrating on the anatomical features of the cardiac components and determining how best they can be described. Appropriate manipulation of developing mice produces unequivocal evidence of isomerism of the atrial appendages, but with no evidence of ventricular isomerism. In hearts from patients with so-called "heterotaxy," only the atrial appendages, distinguished on the basis of the pectinate muscles lining their walls, are uniformly isomeric, permitting the syndrome to be differentiated into the subsets of left as opposed to right atrial appendage isomerism. Thus, controversies are defused by simply describing the isomerism of the atrial appendages rather than "atrial isomerism," recognizing the frequency of abnormal venoatrial connections in these settings. Any suggestion of ambiguity is removed by the equally simple expedient of describing all the variable cardiac features, describing the arrangements of the thoracic and abdominal organs separately should there be discordances.

Correlation between COVID-19 infection and fetal situs inversus.

BACKGROUND: Situs inversus is a rare congenital condition, defined by the mirror-image transposition of the abdominothoracic organs. It is linked to an increased risk of different disorders, for example, congenital heart defects and primary ciliary dyskinesia. Recently, some reports have been on the increased incidence of situs inversus after the COVID-19 pandemic. OBJECTIVES: To investigate the association between maternal COVID-19 infection and fetal situs inversus occurrence risk. METHODS: All pregnant women who underwent fetal ultrasound examinations at Jinan Maternal and Child Health Hospital from January to May of 2022 and 2023 were recruited. A chi-square test was conducted to assess the association of maternal COVID-19 infection with the incidence rate of fetal situs inversus. RESULTS: A total of 8381 patients, including 25 with situs inversus fetuses were recruited. A total of 3956 patients had COVID-19, while 4400 did not. Among 25 mothers with situs inversus fetuses, 22 had COVID-19 and 3 without recent infection. Our analysis showed a strong link between COVID-19 and a higher risk of fetus situs inversus (P < .001, odds ratio 8.196). CONCLUSION: Maternal COVID-19 infection in the early stages of the pregnancy is associated with an increased risk of fetal situs inversion occurrence. Therefore, further research in this field seems necessary.

Atresia biliar sindrómica en un paciente pediátrico: Reporte de caso / Case Report of Syndromic Biliary Atresia in a Pediatric Patient

La atresia de vías biliares es una colangiopatía obstructiva neonatal de etiología desconocida que produce una lesión del parénquima hepático y de la vía biliar intrahepática y extrahepática. Representa la causa más común de colestasis neonatal y trasplante hepático en la población pediátrica y se manifiesta como malformación aislada en la mayoría de los casos. Se presenta un caso de un paciente de 75 días de vida con atresia de vías biliares asociado a heterotaxia abdominal. El síndrome de atresia biliar y malformación esplénica ha sido descrito previamente como atresia de vías biliares asociado a malformaciones anatómicas del bazo, páncreas, alteraciones cardíacas y en menor frecuencia malformaciones genitourinarias. El pronóstico de los pacientes con atresia de vías biliares ha mejorado notoriamente con el reconocimiento temprano de los signos semiológicos y con la realización de la portoenterostomía (Kasai) en forma oportuna para lograr mejorar la sobrevida de los pacientes con atresia de vías biliares sindrómica.

Biliary atresia is an obstructive neonatal cholangiopathy of unknown etiology that produces damage to the parenchyma of the liver and to the intrahepatic and extrahepatic bile ducts. It is the most common cause of neonatal cholestasis and liver transplantation in the pediatric population. In most cases it manifests as an isolated malformation. This article presents the case of a 75 day old patient with biliary atresia associated with abdominal heterotaxy. Biliary atresia syndrome together with splenic malformation has been previously described, as have biliary atresia associated with anatomical malformations of the spleen, pancreas, and heart. It occurs with genitourinary malformations less frequently. The prognosis of patients with biliary atresia has significantly improved with early recognition of signs and symptoms and timely performance of hepatoportoenterostomy (Kasai portoenterostomy).