Language：English   Publisher：AJP Reports  

Ductus arteriosus aneurysm (DAA) asymptomatically occurs in newborn infants and resolves spontaneously. High-risk DAA with compression, rupture, and thrombosis requires early surgical intervention. Newborn infants have the highest risk of thrombosis among pediatric patients, but the genetic predisposition is difficult to determine in infancy. We herein report a neonatal case of massive thromboses in DAA and pulmonary artery. Desaturation occurred in an active full-term infant 2 days after birth. Echocardiography and contrast-enhanced computed tomography indicated thrombotic occlusion of the DAA and pulmonary artery thrombus. Urgent thrombectomy and ductus resection were successfully performed. After 6 months of anticoagulant therapy, the dissociated low plasma activity levels of protein S from protein C suggested protein S deficiency. A genetic study of PROS1 identified a heterozygous variant of protein S K196E, a low-risk variant of thrombophilia in Japanese populations. There have been seven reported cases with neonatal-onset symptomatic thromboses of DAA involving the pulmonary artery. All survived without recurrence after surgical intervention in five and anticoagulant therapy alone in two. Two newborns had a heterozygous methylenetetrahydrofolate reductase (MTHFR) variant, but information on thrombophilia was not available for any other cases. A genetic predisposition may raise the risk of DAA thrombosis, leading to rapid progression.

DOI： 10.1055/a-2101-7738

Web of Science

Scopus

PubMed

Language：English   Publisher：Pediatric Blood and Cancer  

DOI： 10.1002/pbc.30047

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：The Japanese Society of Hematology  

<p>The number of reports on genetic predisposition to pediatric thrombosis is increasing. The risk of thrombosis in childhood varies according to patient age, and the contribution of genetic predisposition also differs. The term early-onset thrombophilia, which occurs until the age of 20 years in patients with genetic diagnosis, was defined. Then, the registry in Japan was established. Further, publications were reviewed comprehensively, and results revealed the genetic and clinical characteristics of patients. Less than 60% of patients presented with protein C (PC) deficiency, and over half of them had PC-gene monoallelic variants. The number of patients with protein S or antithrombin deficiency increased with age. None of them were aged between 6 and 8 years. PC-Tottori and protein S-Tokushima, which are high-frequency and low-risk variants in Japanese, contributed to the development of thrombosis. However, PC-Tottori did not affect the development of severe PC deficiency. One exceptional <i>de novo</i> PC-deficient variant was identified in 32 EOT families, and thrombosis developed concurrently in three pairs of mothers-newborns. Appropriate EOT screening tests targeting PC deficiency are required to prevent maternal and neonatal thromboses.</p>

DOI： 10.11406/rinketsu.64.1131

PubMed

CiNii Research

Language：English   Publisher：Pediatric Pulmonology  

Pulmonary veno-occlusive disease (PVOD) and idiopathic/heritable pulmonary arterial hypertension (I/HPAH) cause progressive PH on the distinct genetic impact. A 29-month-old boy presented with a loss of consciousness. He had severe PH refractory to pulmonary vasodilators. Hypoxemia and ground-glass opacity on the chest computed tomography were present, and significant pulmonary edema developed after the introduction of continuous intravenous prostaglandin I2. Based on the clinical diagnosis of PVOD, he underwent a single living-donor lobar lung transplantation with the right lower lobe of his mother. The pathological findings of his explanted lung showed intimal thickening and luminal narrowing of the pulmonary vein. A genetic test revealed a novel heterozygous splice acceptor variant (c.77-2A>C) in BMPR2, which is typically associated with I/HPAH. This is the first pediatric case of PVOD with BMPR2 variant, supporting the concept that I/HPAH and PVOD are part of a spectrum of pulmonary vascular disease.

DOI： 10.1002/ppul.25877

Web of Science

Scopus

PubMed

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Language：Japanese   Publisher：(株)先端医学社