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Research Paper|Volume 17, Issue 7|pp 1667—1678

National survey of Hutchinson-Gilford progeria syndrome and progeroid laminopathy in Japan

Yuko Okawa1, Muneaki Matsuo2, Rika Kosaki3, Hidefumi Tonoki8, Masanobu Fujimoto9, Keiichi Ozono4,6, Hiroyuki Saitou5,7, Takuo Kubota4, Yasuhisa Ohata4, Noriyuki Namba9, Shinjiro Akaboshi10, Hirofumi Komaki11, Natsuko Inagaki12, Eiko Kato13, Yoshihiro Maruo14, Takahiro Yonekawa15, Tomomi Nakamura15, Katsuhiro Hayashi16, Shinji Miwa16, Miyuki Magota17, Kenji Ihara1
  • 1Department of Pediatrics, Faculty of Medicine, Oita University, Yufu, Oita, Japan
  • 2Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
  • 3Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan
  • 4Department of Pediatrics, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan
  • 5Medical Center for Translational Research Department of Medical Innovation, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan
  • 6Center for Promoting Treatment of Intractable Diseases, Iseikai International General Hospital, Osaka, Japan
  • 7Department of Pediatrics, Iseikai International General Hospital, Osaka, Japan
  • 8Medical Genetics Center, Department of Pediatrics, Tenshi Hospital, Sapporo, Hokkaido, Japan
  • 9Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan
  • 10Department of Pediatrics, NHO Tottori Medical Center, Tottori, Japan
  • 11Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
  • 12Department of Clinical Genetics Center, Tokyo Medical University, Tokyo, Japan
  • 13Department of Pediatrics, Tosei General Hospital, Aichi, Japan
  • 14Department of Pediatrics, Shiga University of Medical Science, Otsu, Shiga, Japan
  • 15Department of Pediatrics, Mie University, Tsu, Mie, Japan
  • 16Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
  • 17Department of Pediatrics, Yaeyama Hospital, Ishigaki, Okinawa, Japan
Received: April 2, 2025Accepted: July 1, 2025Published: July 9, 2025
https://doi.org/10.18632/aging.206277

Copyright: © 2025 Okawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background and Aim: Hutchinson-Gilford Progeria Syndrome (HGPS) and progeroid laminopathies (PL) are rare genetic disorders characterized by accelerated aging and early onset cardiovascular complications. Despite recent advances in the genetic diagnosis of HGPS and PL and the advent of lonafarnib treatment, the epidemiology and clinical characteristics of these disorders in Asia remain unclear. This study aimed to assess the prevalence, clinical features, and diagnostic trends of the HGPS and PL in Japan.

Methods: A nationwide two-step survey was conducted between July 2022 and January 2024, across 1,513 medical facilities.

Results: The survey identified ten HGPS patients, including eight with a confirmed genetic diagnosis. Early onset features such as scleroderma-like skin changes, growth retardation, and joint contracture were important in facilitating an early and accurate diagnosis. Cardiovascular complications typically occurred during their teens, and abnormalities in lipid metabolism were frequently observed. Overlapping but distinct phenotypes have been noted in ZMPSTE24 deficiency and other laminopathies caused by LMNA pathogenic variants, such as Emery-Dreifuss muscular dystrophy. Four patients with definite HGPS and eight patients with progerin-related PL (definite HGPS, n = 4; uncertain HGPS, n = 2; ZMPSTE24 deficiency, n = 2) were reported alive on October 2023, and the prevalence of HGPS was estimated to be 1 in 15.5 to 31.1 million.

Conclusions: This study provides updated epidemiological and clinical insights into HGPS and related laminopathies in Japan. The introduction of lonafarnib has the potential to extend survival, emphasizing the need to monitor for late-stage complications.