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01.09.2012 | Original Article

A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome

verfasst von: Robert H. Cleveland, Leslie B. Gordon, Monica E. Kleinman, David T. Miller, Catherine M. Gordon, Brian D. Snyder, Ara Nazarian, Anita Giobbie-Hurder, Donna Neuberg, Mark W. Kieran

Erschienen in: Pediatric Radiology | Ausgabe 9/2012

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Abstract

Background

Progeria is a rare segmental premature aging disease with significant skeletal abnormalities. Defining the full scope of radiologic abnormalities requires examination of a large proportion of the world’s progeria population (estimated at 1 in 4 million). There has been no comprehensive prospective study describing the skeletal abnormalities associated with progeria.

Objective

To define characteristic radiographic features of this syndrome.

Materials and methods

Thirty-nine children with classic progeria, ages 2–17 years, from 29 countries were studied at a single site. Comprehensive radiographic imaging studies were performed.

Results

Sample included 23 girls and 16 boys—the largest number of patients with progeria evaluated prospectively to date. Eight new and two little known progeria-associated radiologic findings were identified (frequencies of 3–36%). Additionally, 23 commonly reported findings were evaluated. Of these, 2 were not encountered and 21 were present and ranked according to their frequency. Nine abnormalities were associated with increasing patient age (P = 0.02–0.0001).

Conclusion

This study considerably expands the radiographic morphological spectrum of progeria. A better understanding of the radiologic abnormalities associated with progeria and improved understanding of the biology of progerin (the molecule responsible for this disease), will improve our ability to treat the spectrum of bony abnormalities.

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

Eriksson M, Brown WT, Gordon LB et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298PubMedCrossRef

Goldman RD, Goldman AE, Shumaker DK (2005) Nuclear lamins: building blocks of nuclear structure and function. Novartis Found Symp 264:3–16, discussion 16–21, 227–230PubMedCrossRef

Bridger JM, Kill IR (2004) Aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis. Exp Gerontol 39:717–724PubMedCrossRef

Goldman RD, Shumaker DK, Erdos MR et al (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 101:8963–8968PubMedCrossRef

McClintock D, Gordon LB, Djabali K (2006) Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. Proc Natl Acad Sci USA 103:2154–2159PubMedCrossRef

Olive M, Harten I, Mitchell R et al (2010) Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol 30:2301–2309PubMedCrossRef

Amati F, Biancolella M, D'Apice MR et al (2004) Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays. Gene Expr 12:39–47PubMedCrossRef

Csoka AB, English SB, Simkevich CP et al (2004) Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell 3:235–243PubMedCrossRef

10.

Park WY, Hwang CI, Kang MJ et al (2001) Gene profile of replicative senescence is different from progeria or elderly donor. Biochem Biophys Res Commun 282:934–939PubMedCrossRef

11.

Hennekam RC (2006) Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 140:2603–2624PubMed

12.

Kieran MW, Gordon L, Kleinman M (2007) New approaches to progeria. Pediatrics 120:834–841PubMedCrossRef

13.

Gordon LB, McCarten KM, Giobbie-Hurder A et al (2007) Disease progression in Hutchinson-Gilford progeria syndrome: impact on growth and development. Pediatrics 120:824–833PubMedCrossRef

14.

Taybi H, Lachman R (1996) Progeria. In: Radiology of syndromes, metabolic disorders, and skeletal dysplasia, 4th edn. Mosby Year-Book, St. Louis, MO, pp 401–403

15.

Progeria syndrome (Hutchinson-Gilford syndrome) (2006) In: Jones K (ed) Smith’s recognizable patterns of human malformation, 6th edn. W.B. Saunders Co., Philadelphia, PA, pp 146–149

16.

Gordon CM, Gordon LB, Snyder BD et al (2011) Hutchinson-Gilford progeria is a skeletal dysplasia. J Bone Miner Res 26:1670–1679PubMedCrossRef

17.

Merideth MA, Gordon LB, Clauss S et al (2008) Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 358:592–604PubMedCrossRef

18.

Rosenthal IM, Bronstein IP, Dallenback FD et al (1956) Progeria: report of a case with cepalometric roentgenograms and abnormally high concentrations of lipoproteins in serum. Pediatrics 18:565–577PubMed

19.

Poznanski A (1984) Metabolic bone disease and other abnormalities of the hand. In: The hand in radiologic diagnosis. W.B. Saunders Co., Philadelphia, PA, pp 839–894

20.

Margolin FR, Steinbach HL (1968) Progeria Hutchinson-Gilford syndrome. AJR 103:173–178

21.

Resnick D (2002) Additional congenital or heritable anomalies and syndromes. In: Resnick D (ed) Diagnosis of bone and joint disorders, 4th edn. W.B. Saunders Co., Philadelphia, PA, pp 4561–4631

22.

Taybi H, Lachman R (1996) Epiphysis: dense, sclerotic, ivory. In: Radiology of syndromes, metabolic disorders, and skeletal dysplasia, 4th edn. Mosby Year-Book, St. Louis, MO, p 1029

23.

Resnick D (2002) Spinal anomalies and curvatures. In: Resnick D (ed) Diagnosis of bone and joint disorders, 4th edn. W.B. Saunders Co., Philadelphia, PA, pp 4534–4559

24.

(1959) Greulich W, Pyle S (eds) Radiographic atlas of skeletal development of the hand and wrist. Stanford University Press, Stanford, CA

25.

Louis D, Greene T, Poznanski A (1984) Burns, frostbite, foreign bodies and other traumatic lesions of the hand. In: Poznanski A (ed) The hand in radiologic diagnosis. W.B. Saunders Co., Philadelphia, PA, pp 708–733

26.

Poznanski A (1984) Joint disorders. In: The hand in radiologic diagnosis. W.B. Saunders Co., Philadelphia, PA, pp 791–838

27.

Taybi H, Lachman R (1996) Scleroderma. In: Radiology of syndromes, metabolic disorders, and skeletal dysplasia, 4th edn. Mosby Year-Book, St. Louis, MO, pp 448–450

28.

Resnick D (2002) Internal derangements of joints. In: Resnick D (ed) Diagnosis of bone and joint disorders, 4th edn. W.B. Saunders Co., Philadelphia, PA, pp 3019–3375

29.

Poznanski A (1984) Normal variation and congenital anomalies of the wrist. In: The hand in radiologic diagnosis. W.B. Saunders Co., Philadelphia, PA, pp 181–208

30.

Taybi H, Lachman R (1996) Ulna/ulnar ray: aplasia, hypoplasia. In: Radiology of syndromes, metabolic disorders, and skeletal dysplasia, 4th edn. Mosby Year-Book, St. Louis, MO, p 1044

31.

Taybi H, Lachman R (1996) Madelung deformity. In: Radiology of syndromes, metabolic disorders, and skeletal dysplasia, 4th edn. Mosby Year-Book, St. Louis, MO, p 1036

32.

Taybi H, Lachman R (1996) Pseudoarthrosis. In: Radiology of syndromes, metabolic disorders, and skeletal dysplasia, 4th edn. Mosby Year-Book, St. Louis, MO, pp 1039–1040

33.

Gerhard-Herman M, Smoot LB, Wake N et al (2012) Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome. Hypertension 59:92–97PubMedCrossRef

Titel: A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome
verfasst von: Robert H. Cleveland
Leslie B. Gordon
Monica E. Kleinman
David T. Miller
Catherine M. Gordon
Brian D. Snyder
Ara Nazarian
Anita Giobbie-Hurder
Donna Neuberg
Mark W. Kieran
Publikationsdatum: 01.09.2012
Verlag: Springer-Verlag
Erschienen in: Pediatric Radiology / Ausgabe 9/2012
Print ISSN: 0301-0449
Elektronische ISSN: 1432-1998
DOI: https://doi.org/10.1007/s00247-012-2423-1

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A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome