Laboratory Studies

Abnormalities in serum lipid levels are limited to low high-density lipoprotein levels, which are associated with atherosclerotic disease. Serum low-density lipoprotein and total cholesterol levels are normal in patients with Hutchinson-Gilford progeria syndrome (HGPS).

Elevated levels of hyaluronic acid excretion are seen in the urine of patients with HGPS but are not diagnostic. The significance is unknown.

Imaging Studies

Radiography findings usually begin to manifest within the first or second year of life and most commonly involve the skull, thorax, long bones, and phalanges.^{[26, 31]}Typical findings are as follows:

Generalized osteopenia
Acroosteolysis (distal bone resorption) of the phalanges and distal clavicles
Pseudoarthrosis of the distal clavicle
"Fish-mouth" vertebral bodies
Coxa valga and hip dysplasia
Attenuated cortical bone
Widened metaphyses, epiphyseal overgrowth, and narrow diaphyses
Avascular necrosis of the femoral head
Focal concave cortical defects at or near to the insertion of a major muscle group
Dystrophic calcification, typically distal to the tufts of the fingers
Normal bone age

Use of CT and MRI has identified a spectrum of craniofacial structural bone and soft tissue abnormalities.^[32]Common craniofacial abnormalities seen in progeria include the following:

J-shaped sella
Increased calvarial vascular markings
Abnormal mandibular condyles
Hypoplastic articular eminences
Small zygomatic arches
Prominent parotid glands
Optic nerve kinking

Brain magnetic resonance angiography may identify cerebrovascular occlusive disease. Features of a distinct vasculopathy may be seen, including intracranial steno-occlusive arterial lesions, basal cistern collateral vessels, and slow compensatory collateral flow over the cerebral convexities; vertebral artery stenosis with stenosis and calcification of both the cervical internal and common carotid arteries; and high percentage of both early symptomatic and clinically silent infarcts.^[33]

Other Tests

Serial ECG and echocardiography should be performed to monitor for coronary artery disease and congestive heart failure.

Histologic Findings

Skin biopsy specimens from firm, sclerotic areas reveal the characteristics of scleroderma.

In the early stages, the epidermis appears moderately acanthotic with some effacement of the rete ridges. Thickened collagen bundles may be seen in the dermis. Progressive deposition of thickened, homogenized collagen that extends into the subcutaneous tissue is observed. In the upper dermis, a mild perivascular infiltrate may be observed. The amount of acid mucopolysaccharides is increased.

At later stages, the subcutaneous fat is greatly reduced, except for some sparse fat lobules surrounded by connective tissue. Hyalinized dermal collagen is prominent. Blood vessels exhibit a moderate thickening of the muscle wall with a narrowing of the vascular lumen. Hair follicles may appear atrophic.

Treatment & Management

Hutchinson J. A case of congenital absence of hair with atrophic condition of the skin and its appendages. Lancet. 1886. 1:923.
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. Transactions of the Medico-Chirurgical Society of Edinburgh. 1886. 69:473-7.
Gilford H. On a condition of mixed premature and immature development. Medico-Chirurgical Transactions. 80:17-45.
Gilford H. Progeria: a form of senilism. Practitioner. 1904. 73:188-217.
Gilford H. Ateliosis and progeria: contniuous youth and premature old age. Br Med J. 1904. 2:914-8.
Gordon CM, Gordon LB, Snyder BD, Nazarian A, Quinn N, Huh S, et al. Hutchinson-gilford progeria is a skeletal dysplasia. J Bone Miner Res. 2011 Jul. 26(7):1670-9. [QxMD MEDLINE Link].
Ding SL, Shen CY. Model of human aging: recent findings on Werner's and Hutchinson-Gilford progeria syndromes. Clin Interv Aging. 2008. 3(3):431-44. [QxMD MEDLINE Link].
Stehbens WE, Wakefield SJ, Gilbert-Barness E, Olson RE, Ackerman J. Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc Pathol. 1999 Jan-Feb. 8(1):29-39. [QxMD MEDLINE Link].
McClintock D, Gordon LB, Djabali K. Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. Proc Natl Acad Sci U S A. 2006 Feb 14. 103(7):2154-9. [QxMD MEDLINE Link]. [Full Text].
Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, et al. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol. 2010 Nov. 30(11):2301-9. [QxMD MEDLINE Link]. [Full Text].
Gerhard-Herman M, Smoot LB, Wake N, Kieran MW, Kleinman ME, Miller DT, et al. Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome. Hypertension. 2012 Jan. 59(1):92-7. [QxMD MEDLINE Link]. [Full Text].
Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human aging. Science. 2006 May 19. 312(5776):1059-63. [QxMD MEDLINE Link]. [Full Text].
Pereira S, Bourgeois P, Navarro C, Esteves-Vieira V, Cau P, De Sandre-Giovannoli A. HGPS and related premature aging disorders: from genomic identification to the first therapeutic approaches. Mech Ageing Dev. 2008 Jul-Aug. 129(7-8):449-59. [QxMD MEDLINE Link].
Dechat T, Pfleghaar K, Sengupta K, et al. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. 2008 Apr 1. 22(7):832-53. [QxMD MEDLINE Link].
Cao H, Hegele RA. LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet. 2003. 48(5):271-4. [QxMD MEDLINE Link].
Dechat T, Shimi T, Adam SA, et al. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc Natl Acad Sci U S A. 2007 Mar 20. 104(12):4955-60. [QxMD MEDLINE Link].
Bar DZ, Arlt MF, Brazier JF, Norris WE, Campbell SE, Chines P, et al. A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome. J Med Genet. 2016 Dec 5. [QxMD MEDLINE Link].
Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL. A progeroid syndrome in mice is caused by defects in A-type lamins. Nature. 2003 May 15. 423(6937):298-301. [QxMD MEDLINE Link].
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 Aug. 3(4):235-43. [QxMD MEDLINE Link].
Park WY, Hwang CI, Kang MJ, et al. Gene profile of replicative senescence is different from progeria or elderly donor. Biochem Biophys Res Commun. 2001 Apr 13. 282(4):934-9. [QxMD MEDLINE Link].
Ly DH, Lockhart DJ, Lerner RA, Schultz PG. Mitotic misregulation and human aging. Science. 2000 Mar 31. 287(5462):2486-92. [QxMD MEDLINE Link].
Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J Cell Sci. 2006 Nov 15. 119(Pt 22):4644-9. [QxMD MEDLINE Link].
Gordon LB, Massaro J, D'Agostino RB Sr, Campbell SE, Brazier J, Brown WT, et al. Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation. 2014 Jul 1. 130 (1):27-34. [QxMD MEDLINE Link].
Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008 Feb 7. 358(6):592-604. [QxMD MEDLINE Link].
Hennekam RC. Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A. 2006 Dec 1. 140(23):2603-24. [QxMD MEDLINE Link].
Gordon LB, McCarten KM, Giobbie-Hurder A, et al. Disease progression in Hutchinson-Gilford progeria syndrome: impact on growth and development. Pediatrics. 2007 Oct. 120(4):824-33. [QxMD MEDLINE Link].
Rork JF, Huang JT, Gordon LB, Kleinman M, Kieran MW, Liang MG. Initial cutaneous manifestations of Hutchinson-Gilford progeria syndrome. Pediatr Dermatol. 2014 Mar-Apr. 31 (2):196-202. [QxMD MEDLINE Link].
Domingo DL, Trujillo MI, Council SE, Merideth MA, Gordon LB, Wu T, et al. Hutchinson-Gilford progeria syndrome: oral and craniofacial phenotypes. Oral Dis. 2009 Apr. 15(3):187-95. [QxMD MEDLINE Link]. [Full Text].
Guardiani E, Zalewski C, Brewer C, Merideth M, Introne W, Smith AC, et al. Otologic and audiologic manifestations of Hutchinson-Gilford progeria syndrome. Laryngoscope. 2011 Oct. 121(10):2250-5. [QxMD MEDLINE Link]. [Full Text].
Almeida P, Hernandez J, Marti M, Hernandez B. What syndrome is this? Wiedemann-Rautenstrauch syndrome. Pediatr Dermatol. 2005 Jan-Feb. 22(1):75-8. [QxMD MEDLINE Link].
Cleveland RH, Gordon LB, Kleinman ME, Miller DT, Gordon CM, Snyder BD, et al. A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome. Pediatr Radiol. 2012 Sep. 42(9):1089-98. [QxMD MEDLINE Link].
Ullrich NJ, Silvera VM, Campbell SE, Gordon LB. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome. AJNR Am J Neuroradiol. 2012 Sep. 33(8):1512-8. [QxMD MEDLINE Link].
Silvera VM, Gordon LB, Orbach DB, Campbell SE, Machan JT, Ullrich NJ. Imaging characteristics of cerebrovascular arteriopathy and stroke in Hutchinson-Gilford progeria syndrome. AJNR Am J Neuroradiol. 2013 May. 34(5):1091-7. [QxMD MEDLINE Link].
Gordon LB, Shappell H, Massaro J, D'Agostino RB Sr, Brazier J, Campbell SE, et al. Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome. JAMA. 2018 Apr 24. 319 (16):1687-1695. [QxMD MEDLINE Link]. [Full Text].
Meta M, Yang SH, Bergo MO, Fong LG, Young SG. Protein farnesyltransferase inhibitors and progeria. Trends Mol Med. 2006 Oct. 12(10):480-7. [QxMD MEDLINE Link].
Capell BC, Olive M, Erdos MR, et al. A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proc Natl Acad Sci U S A. 2008 Oct 14. 105(41):15902-7. [QxMD MEDLINE Link].
Sagelius H, Rosengardten Y, Schmidt E, Sonnabend C, Rozell B, Eriksson M. Reversible phenotype in a mouse model of Hutchinson-Gilford progeria syndrome. J Med Genet. 2008 Dec. 45(12):794-801. [QxMD MEDLINE Link].
Yang SH, Meta M, Qiao X, et al. A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. J Clin Invest. 2006 Aug. 116(8):2115-21. [QxMD MEDLINE Link].
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 Jan-Feb. 1781(1-2):36-9. [QxMD MEDLINE Link].
Wang Y, Ostlund C, Worman HJ. Blocking protein farnesylation improves nuclear shape abnormalities in keratinocytes of mice expressing the prelamin A variant in Hutchinson-Gilford progeria syndrome. Nucleus. 2010 Jul. 1(5):432-439. [QxMD MEDLINE Link]. [Full Text].
Gordon LB, Kleinman ME, Miller DT, Neuberg DS, Giobbie-Hurder A, Gerhard-Herman M, et al. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2012 Oct 9. 109(41):16666-71. [QxMD MEDLINE Link]. [Full Text].
Ullrich NJ, Kieran MW, Miller DT, Gordon LB, Cho YJ, Silvera VM, et al. Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. Neurology. 2013 Jul 30. 81 (5):427-30. [QxMD MEDLINE Link].
Gordon LB, Kleinman ME, Massaro J, D'Agostino RB Sr, Shappell H, Gerhard-Herman M, et al. Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 2016 Jul 12. 134 (2):114-25. [QxMD MEDLINE Link].
Cao K, Graziotto JJ, Blair CD, Mazzulli JR, Erdos MR, Krainc D, et al. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in hutchinson-gilford progeria syndrome cells. Sci Transl Med. 2011 Jun 29. 3(89):89ra58. [QxMD MEDLINE Link].
Ramos FJ, Chen SC, Garelick MG, Dai DF, Liao CY, Schreiber KH, et al. Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci Transl Med. 2012 Jul 25. 4(144):144ra103. [QxMD MEDLINE Link]. [Full Text].
Cenni V, Capanni C, Columbaro M, Ortolani M, D'Apice MR, Novelli G, et al. Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria. Eur J Histochem. 2011 Oct 19. 55(4):e36. [QxMD MEDLINE Link]. [Full Text].
Graziotto JJ, Cao K, Collins FS, Krainc D. Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders. Autophagy. 2012 Jan. 8(1):147-51. [QxMD MEDLINE Link]. [Full Text].
Gabriel D, Gordon LB, Djabali K. Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype. PLoS One. 2016 Dec 29. 11 (12):e0168988. [QxMD MEDLINE Link].
Pellegrini C, Columbaro M, Capanni C, D'Apice MR, Cavallo C, Murdocca M, et al. All-trans retinoic acid and rapamycin normalize Hutchinson Gilford progeria fibroblast phenotype. Oncotarget. 2015 Aug 13. [QxMD MEDLINE Link].
Sadeghi-Nejad A, Demmer L. Growth hormone therapy in progeria. J Pediatr Endocrinol Metab. 2007 May. 20(5):633-7. [QxMD MEDLINE Link].
Gabriel D, Roedl D, Gordon LB, Djabali K. Sulforaphane enhances progerin clearance in Hutchinson-Gilford progeria fibroblasts. Aging Cell. 2015 Feb. 14 (1):78-91. [QxMD MEDLINE Link].
Lee JM, Nobumori C, Tu Y, Choi C, Yang SH, Jung HJ, et al. Modulation of LMNA splicing as a strategy to treat prelamin A diseases. J Clin Invest. 2016 Apr 1. 126 (4):1592-602. [QxMD MEDLINE Link].

Media Gallery

Early Hutchinson-Gilford progeria syndrome. Note the alopecia, prominent scalp veins, and frontal bossing apparent in this 12-month-old infant with Hutchinson-Gilford progeria syndrome. Midface hypoplasia and micrognathia are less apparent.
Sclerodermatous skin changes in Hutchinson-Gilford progeria syndrome. This 12-month-old infant with Hutchinson-Gilford progeria syndrome has indurated, shiny skin with dyspigmentation.
Sclerodermatous skin changes in Hutchinson-Gilford progeria syndrome. This 12-month-old infant has indurated, shiny skin with dyspigmentation.
Enlarged joints, mild flexion contractures, and sclerodermatous skin changes are seen in this 12-month-old infant with Hutchinson-Gilford progeria syndrome.
Sclerodermatous skin changes in Hutchinson-Gilford progeria syndrome. This 12-month-old infant with Hutchinson-Gilford progeria syndrome has indurated, shiny skin and mild joint contractures involving the extremities and trunk.

of 5

Hutchinson-Gilford Progeria Workup

Laboratory Studies

Imaging Studies

Other Tests

Histologic Findings

References

Tables

Contributor Information and Disclosures

What would you like to print?