Baseline Range of Motion, Strength, Motor Function, and Participation in Youth with Hutchinson-Gilford Progeria Syndrome

Malloy, Julie; Berry, Emily; Correia, Annette; Fragala-Pinkham, Maria; Coucci, Sarah; Riley, Susan; Spratt, J.; Pfaffinger, Jessica Knight; Massaro, Joseph M.; Ehrbar, Rachel Q.; D’Agostino, Ralph B.; Gurary, Ellen B.; Gordon, Leslie B.; Kleinman, Monica E.

doi:10.1080/01942638.2022.2158054

Cited by 2 publications

(2 citation statements)

References 40 publications

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“…Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare, fatal, premature aging disease caused by an autosomal dominant single base mutation in the lamin A/C ( LMNA ) gene encoding the nuclear membrane protein lamin A ( 1 , 2 ). The resulting abnormal protein, called progerin ( 3 ), causes phenotype onset shortly after birth, with lifelong failure to thrive resulting in late teenage heights and weights of around 1.2 m and 18 kg, respectively ( 4 ); total alopecia; sclerodermatous skin changes ( 5 ); abnormal dentition ( 6 ); generalized lipodystrophy; skeletal dysplasia with micro-retrognathia ( 7 , 8 ); joint contractures ( 9 ) and strokes ( 10 ). Without intervention, progressive premature atherosclerosis ( 11 – 14 ) results in death at age 14.5 years on average ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome

Gordon,

Basso,

Maestranzi

et al. 2024

Front. Cardiovasc. Med.

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Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.3 years (30%). With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS has the potential for immediate improvement in healthspan and lifespan. However, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. An international group of experts in HGPS, pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to identify strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases that typify HGPS clinical pathology. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. These breakthrough interventions for treating critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have high impact on treatment success.

show abstract

Section: Introductionmentioning

confidence: 99%

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome

Gordon,

Basso,

Maestranzi

et al. 2024

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare, fatal, premature aging disease caused by an autosomal dominant single base mutation in the lamin A/C (LMNA) gene encoding the nuclear membrane protein lamin A (1,2). The resulting abnormal protein, called progerin (3), causes phenotype onset shortly after birth, with lifelong failure to thrive resulting in late teenage heights and weights of around 1.2 m and 18 kg, respectively(4); total alopecia; sclerodermatous skin changes (5); abnormal dentition(6); generalized lipodystrophy; skeletal dysplasia with micro-retrognathia (7,8); joint contractures (9) and strokes (10). Without intervention, progressive premature atherosclerosis (11)(12)(13) results in death at age 14.5 years on average (14).…”

Section: Introductionmentioning

confidence: 99%

Intervention for Critical Aortic Stenosis in Hutchinson-Gilford Progeria Syndrome

Gordon,

Basso,

Maestranzi

et al. 2023

Preprint

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Background Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending lifespan by several years. With this longer lifespan, calcific aortic stenosis (AS) was identified as an emerging critical risk factor for cardiac death in older patients. Intervention to relieve critical AS in those with HGPS has the potential for immediate improvement in healthspan and lifespan. However, in the face of cardiovascular pathology that is seen almost exclusively in aging adults, HGPS patient-device size mismatch, pervasive peripheral arterial disease, skin and bone abnormalities, and lifelong failure to thrive present unique challenges to intervention. Main Body: An international group of HGPS experts and leaders in pediatric and adult cardiology, cardiac surgery, and pediatric critical care convened to discuss pivotal features of AS progression in HGPS, identifying challenges to and strategies for successful treatment. Candidate procedures were evaluated by in-depth examination of 4 cases of end stage classic HGPS with critical calcific AS that typify the pathology that necessitates individualized surgical risk/benefit assessments. Modified transcatheter aortic valve replacement (TAVR) and left ventricular Apico-Aortic Conduit (AAC) placement were deemed high risk but viable options. Two cases received TAVR and 2 received AAC post-summit. Three were successful and 1 patient died perioperatively due to cardiovascular disease severity, highlighting the importance of intervention timing and comparative risk stratification. Conclusions Modified TAVR and AAC breakthrough interventions for treatment of critical aortic stenosis in HGPS patients could rewrite the current clinical perspective on disease course by greatly improving late-stage quality of life and increasing average lifespan. Expanding worldwide medical and surgical competency for this ultra-rare disease through expert information-sharing could have a high impact on treatment success.

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Baseline Range of Motion, Strength, Motor Function, and Participation in Youth with Hutchinson-Gilford Progeria Syndrome

Cited by 2 publications

References 40 publications

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome

Intervention for Critical Aortic Stenosis in Hutchinson-Gilford Progeria Syndrome

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