無脾症候群

AIM: The aim of this study was to highlight the hypothesis that embryological development and morphological aspects necessitate a comprehensive analysis of all situses and a detailed description of each anomaly, rather than attempting to force the malformation into the rigid categories of heterotaxy syndrome (HS) - left or right isomerism. This hypothesis is supported by describing the anatomy of a complex patient with multiple laterality defects resulting in multiple cardiac and organ malformations. CASE PRESENTATION: The unique aspect of the presented patient's morphological diagnosis lies in the presence of a leftward heart loop with an unusual shape and direction, with the right ventricle (RV) positioned posterosuperior to the left ventricle (LV). This configuration suggests congenitally corrected transposition of the great arteries, although it deviates from the typical presentation. Additionally, there is an arrest in the development of other embryonic structures, including an atrioventricular septal defect (AVSD) with asymmetric ventricles, hypoplasia of the left-sided morphological RV, and malposition of the great arteries, with the aorta positioned anteriorly and to the right of the stenotic pulmonary artery. There is also another important inconsistency: the atrial situs is solitus within the context of HS, accompanied by left bronchial isomerism, polysplenia, interrupted inferior vena cava, and bilateral superior vena cavae. CONCLUSIONS: In our patient's case, the segmental analysis revealed a rare morphological cardiac anatomy. Understanding both normal and pathological embryological cardiac development, and correlating it with the current morphological anatomy, was crucial in ensuring the correct diagnosis and treatment for our patient.

BACKGROUND: Laterality defects are rare congenital malformations that encompass congenital heart defects (CHDs) together with abnormalities of visceral organ arrangement (situs inversus or situs ambiguous). These defects may be isolated or part of a syndromic presentation with multisystem involvement. While over 50 genes have been implicated in laterality disorders, across multiple modes of inheritance, many cases remain molecularly undiagnosed. We sought to elucidate the molecular basis of dextrocardia, CHDs and visceral heterotaxy in two unrelated individuals of Arab-Muslim descent. METHODS: Detailed clinical phenotyping and exome sequencing (ES) were performed for each of the probands, followed by familial segregation analysis. RESULTS: ES revealed a shared homozygous variant in the Dan Domain Family Member 5 (DAND5) gene (NM_152654.3): c.396_397dup, p.(Tyr133SerfsTer11). DAND5 encodes a member of the Cerberus-related DAN protein family, which is involved in the establishment of left body asymmetry. This frameshift variant introduces a premature stop codon within the final exon, which is predicted to escape nonsense-mediated decay (NMD), resulting in a truncated protein lacking the functional DAN domain. CONCLUSIONS: DAND5 has recently been suggested as a candidate gene in heterotaxy and CHDs. Our findings further support biallelic loss of function variants in DAND5 autosomal recessive laterality defects.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare COL3A1-related disorder that predisposes pregnant patients to arterial and visceral rupture. We report a 35-year-old primigravida at 26 weeks who presented with abdominal pain, hemorrhagic shock, and a rapid hemoglobin decrease. CT showed splenic laceration with hemoperitoneum. Emergency laparoscopy was converted to laparotomy because of approximately 2,000 mL of hemoperitoneum and limited access. A 3 cm × 2 cm splenic laceration, friable perisplenic tissues, and diffuse uterine serosal petechiae and oozing without gross rupture were identified. Cesarean delivery was performed because of concern for impending uterine rupture and to facilitate hemorrhage control, followed by splenectomy. The patient survived; the neonate did not. Splenic histopathology showed hemorrhage without malignant or infectious infiltration. Targeted sequencing identified a heterozygous COL3A1 (NM_000090.4):c.1862G > A, p.(Gly621Glu) variant, supporting vEDS. In pregnant patients with unexplained visceral rupture or diffuse tissue bleeding, vEDS should be considered promptly. Early genetic diagnosis and rapid multidisciplinary surgical decision-making may be critical for maternal survival, followed by vascular surveillance, asplenia management, and individualized reproductive counseling.

Sickle cell disease (SCD) is a hereditary haemoglobin abnormality due to a point mutation in the β-globin gene resulting in the production of haemoglobin S. Polymerization of deoxygenated hemoglobin S results in red cell sickling, hemolysis, endothelial injury, ischemia-reperfusion damage, vaso-occlusion, and, in addition to being a hemolytic anaemia and vaso-occlusive condition, SCD is now considered a chronic inflammatory disease with significant immunological abnormalities. This review explores the pathophysiological and immunological basis of SCD, with particular emphasis on how hemolysis, inflammation, innate and adaptive immunity, vulnerability to infection and their implications for current and emerging therapeutics. SCD is characterised by sustained innate and adaptive immune responses, including leukocytosis; neutrophil and monocyte activation; changes in cytokine profiles; complement activation; and T- and B-cell dysfunction. Danger-associated molecular patterns released during hemolysis, including activate inflammasomes, oxidative stress, and endothelial dysfunction through toll-like receptors. Repeat vaso-occlusion maintains sterile inflammation and facilitates coagulation, immune regulation, and vascular damage. Also present are functional asplenia and defective humoral immunity, which predisposes to infection, particularly that caused by encapsulated bacteria. These disruptions help cause vaso-occlusive crises, acute chest syndrome, stroke, pulmonary hypertension, leg ulcers, nephropathy and long-term organ damage. Immunological dysregulation lies at the core of the pathophysiology and complications of SCD. A more detailed understanding of the immune landscape can enhance disease management and inform treatment, including drug administration, transfusion, hematopoietic stem cell transplantation, and gene-based therapies.