Исследование выявило различия в прогнозе и причинах смерти при редких прогероидных синдромах

"Classical laminopathic progeroid syndromes link nuclear-envelope defects to accelerated aging, but the specific prognosis for each subtype remains unclear." BUFFALO, NY — July 6, 2026 — A new systematic review was published in Volume 18 of Aging on June 18, 2026, titled " Life expectancy and causes of death in classical laminopathic progeroid syndromes: systematic review with individual-patient data synthesis ." The study was led by co-first authors Carlos López-Vila, Manuel García-Cordeiro, and Luís Estévez-Martínez from the University of Santiago de Compostela , and corresponding author David Araújo-Vilar from the University of Santiago de Compostela and the University Clinical Hospital of Santiago de Compostela, Spain . Classical laminopathic progeroid syndromes are among the rarest inherited disorders known. Caused by mutations affecting the LMNA gene or the ZMPSTE24 enzyme, these conditions lead to premature aging, severe multisystem disease, and markedly shortened life expectancy. Although Hutchinson-Gilford progeria syndrome (HGPS), mandibuloacral dysplasia (MAD), and restrictive dermopathy (RD) all belong to this group, reliable information about survival and causes of death for each disorder has remained limited because most published reports describe only individual patients or small case series. In this study, researchers performed a comprehensive systematic review and individual-patient data analysis to date of classical laminopathic progeroid syndromes. Following PRISMA guidelines, they analyzed data from 169 published studies together with two additional genetically confirmed institutional cases, creating a cohort of 158 genetically confirmed patients for the primary survival analysis. By examining individual patient records rather than pooled summaries, the investigators were able to compare survival patterns and causes of death across each disease subtype with greater precision. The analysis demonstrated striking differences in life expectancy among the disorders. Patients with Hutchinson-Gilford progeria syndrome had a median survival of 16 years, while those with mandibuloacral dysplasia type B had a median survival of 37 years. In contrast, restrictive dermopathy was associated with extremely poor survival. Median survival was 0.92 years for LMNA-associated restrictive dermopathy and only 0.03 years for ZMPSTE24-associated restrictive dermopathy. No deaths were reported among patients with mandibuloacral dysplasia type A during the available follow-up period. The investigators also found that causes of death differed substantially between disease subtypes. Respiratory failure accounted for most deaths in restrictive dermopathy, reflecting the severe respiratory complications that develop shortly after birth. Cardiovascular disease was the leading cause of death in Hutchinson-Gilford progeria syndrome, consistent with the accelerated vascular aging characteristic of the condition. In mandibuloacral dysplasia type B, renal complications were the most frequently reported fatal events. These findings suggest that each syndrome follows a distinct clinical course despite sharing similar molecular origins. To improve the accuracy of their analysis, the researchers compared genetically confirmed cases with clinically diagnosed cases reported before widespread genetic testing became available. They found that historical clinical diagnoses could influence survival estimates because some earlier reports likely included patients with overlapping disorders. By focusing primarily on genetically confirmed cases, the investigators were able to provide more reliable estimates for prognosis and disease-specific mortality. The study also highlights important implications for patient care. Rather than treating classical laminopathic progeroid syndromes as a single group, the findings support disease-specific monitoring strategies. Patients with HGPS may benefit from careful cardiovascular surveillance, while respiratory management is particularly critical for restrictive dermopathy. Likewise, the results suggest that patients with mandibuloacral dysplasia type B may require closer monitoring for progressive kidney disease. "In sum, survival and mortality patterns differ markedly across classical laminopathic progeria; genetically confirmed IPD resolved by subtype provides more reliable estimates for clinical counseling and trial design in ultra-rare progeroid disorders." According to the authors, these findings provide a stronger foundation for clinical counseling, patient management, and future therapeutic trials. They also emphasize the importance of genetic confirmation, standardized reporting of causes of death, and long-term patient follow-up to improve understanding of these exceptionally rare disorders. Overall, this study provides the most comprehensive comparison to date of survival and mortality across classical laminopathic progeroid syndromes. By synthesizing genetically confirmed individual-patient data from nearly 170 studies, the researchers demonstrate that prognosis differs substantially between disease subtypes, offering valuable information that may improve diagnosis, patient care, and the design of future clinical trials for these rare premature aging disorders. Paper DOI: https://doi.org/10.18632/aging.206389