[Genetic predisposition to early-onset thrombophilia: a study on challenges in personalized medicine for mothers, infants, and children].

Abstract

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 de novo 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.

• Authors: Shouichi Ohga, Naoki Egami, Taeko Hotta, Takeshi Uchiumi, Masayuki Ochiai, Masataka Ishimura
• Journal: [Rinsho ketsueki] The Japanese journal of clinical hematology (Rinsho Ketsueki) Vol. 64 Issue 9 Pg. 1131-1136 ( 2023) ISSN: 0485-1439 [Print] Japan
• PMID: 37899192 (Publication Type: English Abstract, Journal Article)

Topics

• Child
• Humans
• Infant
• Infant, Newborn
• Genetic Predisposition to Disease
• Precision Medicine
• Thrombophilia (genetics, diagnosis)
• Thrombosis
• Protein C Deficiency (diagnosis, genetics)