Clinical and molecular delineation of classical-like Ehlers-Danlos syndrome through a comprehensive next-generation sequencing-based screening system.

Classical-like Ehlers-Danlos syndrome (clEDS) is an autosomal recessive disorder caused by complete absence of tenascin-X resulting from biallelic variation in TNXB. Thus far, 50 patients from 43 families with biallelic TNXB variants have been identified. Accurate detection of TNXB variants is challenging because of the presence of the pseudogene TNXA, which can undergo non-allelic homologous recombination. Therefore, we designed a genetic screening system that is performed using similar operations to other next-generation sequencing (NGS) panel analyses and can be applied to accurately detect TNXB variants and the recombination of TNXA-derived sequences into TNXB. Using this system, we identified biallelic TNXB variants in nine unrelated clEDS patients. TNXA-derived variations were found in >75% of the current cohort, comparable to previous reports. The current cohort generally exhibited similar clinical features to patients in previous reports, but had a higher frequency of gastrointestinal complications (e.g., perforation, diverticulitis, gastrointestinal bleeding, intestinal obstruction, rectal/anal prolapse, and gallstones). This report is the first to apply an NGS-based screening for TNXB variants and represents the third largest cohort of clEDS, highlighting the importance of increasing awareness of the risk of gastrointestinal complications.

The detailed obstetric course of the first Japanese patient with AEBP1-related Ehlers-Danlos syndrome (classical-like EDS, type 2).

We reported a detailed obstetric course of a Japanese patient with Ehlers-Danlos syndrome (EDS) caused by biallelic pathogenic variants in the AEBP1 gene. She was diagnosed with classical EDS at 3 years of age. At 33 years, whole-exome sequencing revealed a homozygous nonsense variant (c.1894C > T:p.Arg632*) in AEBP1. This is the 10th case of AEBP1-related EDS (classical-like EDS type 2) and the first in Japan. She was managed as an inpatient at our hospital beginning at 20 weeks of gestation because of the possibility of high-risk pregnancy. She experienced painful urinary retention, migraines, and threatened premature labor. She delivered a healthy female via elective caesarean section at 32 weeks of gestation. She was treated in the intensive care unit for severe paralytic ileus, postoperatively. Conservative therapy resulted in favorable outcomes, and she was safely discharged on postdelivery day 22nd.

Remarkable response of recurrent endometrial adenocarcinoma to daily oral administration of half-dose etoposide.

A 71-year-old woman with right chest and left lumbar pain was referred to our hospital. Computed tomography showed multiple recurrent tumors in the abdominal cavity and bilateral lungs. She had already received several chemotherapies for the recurrent tumor, and palliative care would be appropriate. However, she was seeking another anti-cancer therapy. Therefore, she was told about low-dose etoposide therapy and consented to its administration. Treatment was very effective; serum tumor marker levels decreased dramatically, the pain was controlled, and the recurrent masses were shrinking. However, her recurrent tumor had become refractory again in the 22nd month of treatment.

A thick placenta: a predictor of adverse pregnancy outcomes.

PURPOSE: The aim of this study is to evaluate the efficacy of an ultrasonographic measurement of placental thickness and the correlation of a thick placenta with adverse perinatal outcome. METHODS: Placental thickness was measured in single gravidas, 16 to 40 weeks of gestation, between 2005 and 2009. Placentas were considered to be thick if their measured thickness were above the 95th percentile for gestational age. RESULTS: The incidence of thick placentas was 4.3% (138/3,183). Perinatal morbidity and neonatal conditions were worse in cases with thick placenta rather than without thick placenta. CONCLUSIONS: Ultrasonographic measurement of placental thickness is a simple method to estimate placental size. Thick placenta may be a useful predictor of adverse pregnancy outcomes.

A case of pregnancy associated hypereosinophilia with hyperpermeability symptoms.

BACKGROUND: Hypereosinophilia commonly reflects an allergic, infectious, or neoplastic disease, and is a rare complication during pregnancy. CASE: A 27-year-old pregnant woman was referred to our hospital due to dyspnea at 10 weeks' gestation. Ultrasound examination showed the presence of pericardial effusion, pleural effusion, and ascites. Fluid transfusion, diuretic administration, and oxygen supplementation gradually improved the symptoms. Thereafter, the blood eosinophil count increased acutely and the fetus died. Following cessation of pregnancy the blood eosinophil count gradually decreased. Laboratory examinations did not assist the diagnosis of eosinophilia. CONCLUSION: This is the first case of hypereosinophilia associated with the life-threatening hyperpermeability symptoms, i.e., pericardial effusion, pleural effusion, and ascites, during early pregnancy.