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.