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Hutchinson-Gilford Progeria Syndrome

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Neurocutaneous Disorders

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Abstract

Hutchinson-Gilford progeria syndrome has an incidence of approximately 1 in 4–eight million live births. The newborns are normal at birth, but between the first and the second year of life, they begin to display accelerated ageing in growth and skin. HGPS is an autosomal dominant, fatal childhood disorder. Progeria is called a segmental premature ageing syndrome – it induces early cellular senescence that is associated with increased DNA-damage signalling, linked to mutations in the LMNA gene that encodes for type-A nuclear lamins. The most common HGPS mutation is found at position G608G within exon 11 of the LMNA gene. This mutation results in the deletion of 50 amino acids at the carboxyl-terminal tail of prelamin A. The truncated protein is called progerin, which accumulates in HGPS nuclei and is the hallmark of the disease. Targeted therapy, lonafarnib, a farnesyltransferase inhibitor, has been approved as a first-line treatment for HGPS.

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References

  1. Hutchinson J. Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Lancet. 1886;1:923.

    Google Scholar 

  2. Gilford H. Ateleiosis and progeria: continuous youth and premature old age. Br Med J. 1904;2:914–8.

    Google Scholar 

  3. Fossel M. The progerias. J Anti Aging Med. 2003;6:123–38.

    Article  Google Scholar 

  4. Ahmed MS, Ikram S, Bibi N, Mir A. Hutchinson-Gilford progeria syndrome: a premature aging disease. Mol Neurobiol. 2018;55:4417–27.

    CAS  PubMed  Google Scholar 

  5. Cao H, Hegele RA. LMNA is mutated in Hutchinson-Gilford progeria but not in Wiedemann-Rautenstrauch progeroid syndrome. J Hum Genet. 2003;48:271–4.

    Article  CAS  Google Scholar 

  6. De Sandre-Giovannoli A, Bernard R, Cau P, et al. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300(5628):2055.

    Article  Google Scholar 

  7. Eriksson M, Brown WT, Gordon LB, et al. Recurrent de novo point mutations in Lamin a cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423(6937):293–8.

    Article  CAS  Google Scholar 

  8. Progeria Research Foundation International Progeria Registry. www.progeriaresearch.org/international-registry/

  9. Csoka AB, English SB, Simkevich CP, et al. Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell. 2004;3:235–43.

    Article  CAS  Google Scholar 

  10. Wallis CV, Sheerin AN, Green MH, et al. Fibroblast clones from patients with Hutchinson-Gilford progeria can senesce despite the presence of telomerase. Exp Gerontol. 2004;39:461–7.

    Article  CAS  Google Scholar 

  11. Pollex RL, Hegele RA. Hutchinson-Gilford progeria syndrome. Clin Genet. 2004;66:375–81.

    Article  CAS  Google Scholar 

  12. Kirschner J, Brune T, Wehnert M, et al. S143F mutation in Lamin a/C: a new phenotype combining myopathy and progeria. Ann Neurol. 2005;57:148–51.

    Article  CAS  Google Scholar 

  13. Gabriel D, Roedl D, Leslie B, et al. Sulforaphane enhances progerin clearance in Hutchinson–Gilford progeria fibroblasts. Aging Cell. 2014;14:78–91.

    Article  Google Scholar 

  14. Kreienkamp R, Gonzalo S. Metabolic dysfunction in Hutchinson-Gilford Progeria syndrome. Cell. 2020;9:395.

    Article  CAS  Google Scholar 

  15. Hennekam RC. Hutchinson-Gilford progeria syndrome: a review of the phenotype. Am J Med Genet A. 2006;140:2603–24.

    Article  Google Scholar 

  16. Harhouri K, Frankel D, Bartoli C, et al. An overview of treatment strategies for Hutchinson-Gilford Progeria syndrome. Nucleus. 2018;1(9):246–57.

    Google Scholar 

  17. Gerhard-Herman M, Smoot LB, Wake N, et al. Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome. Hypertension. 2012;59:92–7.

    Article  CAS  Google Scholar 

  18. Rork JF, Huang JT, Gordon LB, et al. Initial cutaneous manifestations of Hutchinson-Gilford progeria syndrome. Pediatr Dermatol. 2014;31:196–202.

    Article  Google Scholar 

  19. Xu S, Jin ZG. Hutchinson-Gilford Progeria Syndrome: Cardiovascular Pathologies and Potential Therapies. Trends Biochem Sci. 2019;44:561–4.

    Article  CAS  Google Scholar 

  20. Silvera VM, Gordon LB, Orbacha DB, et al. Imaging characteristics of cerebrovascular Arteriopathy and stroke in Hutchinson-Gilford progeria syndrome. Am J Neuroradiol. 2013;34:1091–7.

    Article  CAS  Google Scholar 

  21. Chiplunkar S, Bindu PS, Nagappa M, et al. Hutchinson syndrome. Metab Brain Dis. 2016;31:1195–8.

    Article  Google Scholar 

  22. Gordon LB, Rothman FG, Lopez-Otin C, Misteli T. Progeria: a paradigm for translational medicine. Cell. 2014;156:400–7.

    Article  CAS  Google Scholar 

  23. Kashyap S, Shanker V, Sharma N. Hutchinson-Gilford progeria syndrome: a rare case report. Indian Dermatol Online J. 2014;5:478–81.

    Article  Google Scholar 

  24. Dyer CA, Sinclair AJ. The premature aging syndromes: insights into the ageing process. Age Ageing. 1998;27:73–80.

    Article  CAS  Google Scholar 

  25. Shah-Desai S, Sandy C, Collin R. Lax eyelid syndrome or “progeria” of eyelid tissues. Orbit. 2004;23:3–12.

    Article  Google Scholar 

  26. Batstone MD, Macleod AWG. Oral and maxillofacial surgical considerations for a case of Hutchinson-Gilford progeria. Inter J Paediatric Dentistry. 2002;12:429–32.

    Article  CAS  Google Scholar 

  27. Villa F, Maciag A, Spinelli CC, et al. A G613A missense in the Hutchinson’s progeria Lamin a/C gene causes a lone, autosomal dominant atrioventricular block. Immun Ageing. 2014;11:19.

    Article  Google Scholar 

  28. Mounkes LC, Stewart CL. Aging and nuclear organization: lamins and progeria. Curr Opin Cell Biol. 2004;16:322–7.

    Article  CAS  Google Scholar 

  29. FDA (2021). http://fda.org/news-events/press-announcements/fda-approves-first-treatment%E2%80%93hutchinson-gilford-progeria-syndrome-and-some-progeroid-laminopathies#:~:test=Today%2C%20th%20U.S.%20Food%20

  30. Yang SH, Qiao X, Fong LG, Young SG. Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation. Biochim Biophys Acta. 2008;283(70):94–109.

    Google Scholar 

  31. Ibrahim MX, Sayin VI, Akula MK, et al. Targeting isoprenylcysteine methylation ameliorates disease in a mouse model of progeria. Science. 2013;340:1330–3.

    Article  CAS  Google Scholar 

  32. Liessmann CD. Anaesthesia in a child with Hutchinson-Gilford progeria. Paediatr Anaesth. 2001;11:611–4.

    Article  CAS  Google Scholar 

  33. Nijs K, Van de Velde M, Hoogma D. Anesthetic considerations in children with Hutchinson-Gilford progeria syndrome: A narrative review. Paediatr Anaesth. 2020;30:537–3.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatric Neurology and Developmental Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Christos P. Panteliadis

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  1. Christos P. Panteliadis
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Editors and Affiliations

  1. Department of Paediatric Neurology and Developmental Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Christos P. Panteliadis

  2. Department of Neurology, University of Washington, Seattle, WA, USA

    Ramsis Benjamin

  3. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Hagel

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Panteliadis, C.P. (2022). Hutchinson-Gilford Progeria Syndrome. In: Panteliadis, C.P., Benjamin, R., Hagel, C. (eds) Neurocutaneous Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-87893-1_40

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  • DOI: https://doi.org/10.1007/978-3-030-87893-1_40

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-87892-4

  • Online ISBN: 978-3-030-87893-1

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