Dysgerminoma Probably Due to a Novel SOHLH1-pathogenic Variant Causing Familial Ovarian Dysgenesis.

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.

Inherited bone marrow failure syndromes: phenotype as a tool for early diagnostic suspicion at a major reference center in Mexico.

Introduction: The inherited bone marrow failure syndromes (IBMFSs) are a group of rare disorders characterized by bone marrow failure (BMF), physical abnormalities, and an increased risk of neoplasia. The National Institute of Pediatrics (INP) is a major medical institution in Mexico, where patients with BMF receive a complete approach that includes paraclinical tests. Readily recognizable features, such as the hematological and distinctive physical phenotypes, identified by clinical dysmorphologists, remain crucial for the diagnosis and management of these patients, particularly in circumstances where next-generation sequencing (NGS) is not easily available. Here, we describe a group of Mexican patients with a high clinical suspicion of an IBMFS. Methods: We performed a systematic retrospective analysis of the medical records of patients who had a high IBMFS suspicion at our institution from January 2018 to July 2021. An initial assessment included first ruling out acquired causes of BMF by the Hematology Department and referral of the patient to the Department of Human Genetics for physical examination to search for specific phenotypes suggesting an IBMFS. Patients with high suspicion of having an IBMFS were classified into two main groups: 1) specific IBMFS, including dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS), thrombocytopenia with absent radii (TAR), and severe congenital neutropenia (SCN); 2) undefined IBMFS (UI). Results: We established a high suspicion of having an IBMFS in 48 patients. At initial evaluation, the most common hematologic features were bicytopenia (20%) and aplastic anemia (16%); three patients received hematopoietic stem cell transplantation. Among patients with a suspicion of an IBMFS, the most common physical abnormality was minor craniofacial features in 83% of patients and neurodevelopmental disorders in 52%. The specific suspicions that we built were DBA (31%), SDS (18%), DC (14%), TAR (4%), and SCN (4%), whereas 27% of cases remained as undefined IBMFS. SDS, TAR, and SCN were more commonly suspected at an earlier age (<1 year), followed by DBA (2 years) and DC (5 years). Conclusions: Thorough examination of reported clinical data allowed us to highly suspect a specific IBMFS in approximately 70% of patients; however, an important number of patients remained with suspicion of an undefined IBMFS. Implementation of NGS and telomere length measurement are forthcoming measures to improve IBMFS diagnosis in Mexico.

Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability.

Inherited bone marrow failure syndromes (IBMFS) are a complex and heterogeneous group of genetic diseases. To date, at least 13 IBMFS have been characterized. Their pathophysiology is associated with germline pathogenic variants in genes that affect hematopoiesis. A couple of these diseases also have genomic instability, Fanconi anemia due to DNA damage repair deficiency and dyskeratosis congenita/telomere biology disorders as a result of an alteration in telomere maintenance. Patients can have extramedullary manifestations, including cancer and functional or structural physical abnormalities. Furthermore, the phenotypic spectrum varies from cryptic features to patients with significantly evident manifestations. These diseases require a high index of suspicion and should be considered in any patient with abnormal hematopoiesis, even if extramedullary manifestations are not evident. This review describes the disrupted cellular processes that lead to the affected maintenance of the genome structure, contrasting the dysmorphological and oncological phenotypes of Fanconi anemia and dyskeratosis congenita/telomere biology disorders. Through a dysmorphological analysis, we describe the phenotypic features that allow to make the differential diagnosis and the early identification of patients, even before the onset of hematological or oncological manifestations. From the oncological perspective, we analyzed the spectrum and risks of cancers in patients and carriers.

Factors that impact kidney function during open and endovascular reconstruction of aortic aneurysms.

BACKGROUND: To analyze the factors that influence the deterioration of postoperative renal function in patients undergoing open or endovascular aortic reconstruction, and the impact on survival. METHOD: Retrospective review of patients who underwent invasive treatment was conducted. Demographics, laboratory data, clinical, intraoperative and postoperative variables were recorded; renal function was determined, Fisher's exact test was used to find associations and Kaplan Meier analysis to estimate survival. RESULTS: From 2007 to 2017, 80 patients (mean age: 70 years) were studied. Fifty-eight (73%) were male, none of these patients had known diagnosis of chronic kidney insufficiency. Twelve (15%) patients had elevated creatinine in the postoperative period; variables such as intraoperative bleeding greater than 1500 ml were associated with acute renal failure (p = 0.005). During the follow-up period of 60 months, 8 (10%) patients progressed to chronic renal failure, 2 (2.5%) requiring hemodialysis, 18 (22%). Age, gender, comorbidities and anatomic characteristics of the aneurysm, type of intervention or level of aortic cross-clamping did not impact the postoperative renal function. CONCLUSIONS: The repair of complex aortic aneurysms continues to be a challenge. Intraoperative bleeding greater than 1500 ml and the need of blood transfusion was associated with deterioration of postoperative renal function, affecting the 5-year survival of patients.

OBJETIVO: Analizar qué factores influyen en el deterioro de la función renal en pacientes sometidos a reconstrucción aórtica abierta o endovascular, y su impacto en la supervivencia. MÉTODO: Estudio retrospectivo. Se analizaron variables demográficas, de laboratorio, transoperatorias y posoperatorias. Se determinó la función renal y se utilizó la prueba exacta de Fisher en la búsqueda de asociaciones, y el análisis de Kaplan-Meier para estimar la supervivencia. RESULTADOS: De 2007 a 2017, 80 pacientes (media de edad: 70 años) fueron sometidos a procedimientos de reconstrucción aórtica. Cincuenta y ocho (73%) eran de sexo masculino. Doce (15%) tuvieron elevación de creatinina en el posoperatorio y sangrado mayor de 1500 ml con necesidad de transfusión que se asoció a insuficiencia renal aguda (p = 0.005). Durante el periodo de seguimiento de 60 meses, 8 (10%) pacientes desarrollaron insuficiencia renal crónica, 2 (2.5%) requirieron hemodiálisis y 18 (22%) fallecieron. La edad, el sexo, la comorbilidad y las características anatómicas del aneurisma, así como el tipo de intervención o el nivel de pinzamiento aórtico, no impactaron la función renal posoperatoria. CONCLUSIONES: La reparación de los aneurismas aórticos complejos continúa siendo un reto. Un sangrado superior a 1500 ml, con necesidad de transfusión, se asoció a deterioro de la función renal posoperatoria e impactó en la supervivencia a 5 años.

Successful Embolization of a Ruptured Ovarian Artery Aneurysm in a Postmenopausal Woman: Case Report and Literature Review of Gonadal Artery Aneurysms.

Gonadal artery aneurysms (GADs) are extremely rare; their prevalence and natural history are unknown and their pathogenesis remains poorly understood. Based on the limited literature reports, these might present with rupture (ovarian artery) or pain and acute thrombosis (testicular artery). The present article reports the case of an 80-year-old woman who came to the emergency department (ED) with acute onset of abdominal and left flank pain. A computed tomography angiography (CTA) revealed a large retroperitoneal hematoma associated with the presence of a left ovarian artery aneurysm. The patient was taken to the angiography suite for a selective vessel catheterization and embolization with N-butyl-2-cyanoacrylate (NBCA). Following the procedure, her serial hemoglobin remained stable, her symptoms subsided, and she was discharged home 2 days later. The GADs are unrecognized entities until an acute event such as rupture occurs, and vessel embolization is effective for hemorrhage control. Close communication and collaboration with gynecologists and urologists are crucial to better define the prevalence, natural history, and the appropriate behavior and timing for elective treatment. With this article, the authors additionally present a review of the literature.