Showing papers by "Stanley G. Rockson published in 2016"

EPHB4 kinase–inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis

Abstract: Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate.

Erratum: Pregnancy Complicated by Gorham-Stout Disease and Refractory Chylothorax.

Abstract: Introduction Gorham–Stout Disease (GSD) is a rare disorder of bony destruction due to lymphangiomatosis, and is often triggered by hormones. One complication of GSD is the development of chylothorax, which carries a high mortality rate. Very little experience has been published to guide management in GSD during pregnancy to optimize both fetal and maternal health. Case Study A 20-year-old woman with known GSD presented with shortness of breath at 18 weeks of pregnancy, due to bilateral chylothoraces which required daily drainage. To minimize chylous fluid formation, she was placed on bowel rest with total parenteral nutrition (limiting lipid intake) and received octreotide to decrease splanchnic blood flow and chylous fluid drainage. Treatment options were limited due to her pregnancy. Twice daily home chest tube drainage of a single lung cavity, total parenteral nutrition, octreotide, and albumin infusions allowed successful delivery of a healthy 37 weeks' gestation infant by cesarean delivery. Discussion This case illustrates the management of a rare clinical disease of bone resorption and lymphangiomatosis complicated by bilateral, refractory chylothoraces, triggered by pregnancy, in whom treatment options are limited, and the need for a multidisciplinary health care team to ensure successful maternal and fetal outcomes.

Ltb4 inhibition to prevent and treat human lymphedema

Abstract: Provided are therapeutic methods for treating a patient with lymphedema, or prophylactically treating an individual susceptible to lymphedema, by inhibiting synthesis activity of leukotriene B 4 .