Progeria, a pathologic study

Gabr, Mohamed; Hashem, Nemat; Hashem, Mohamed; Fahmi, Abdelgawad A.; Safouh, M

doi:10.1016/s0022-3476(60)80213-2

Cited by 69 publications

(40 citation statements)

References 11 publications

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“…30 A few HGPS subjects had diffuse myocardial fibrosis without significant coronary atherosclerosis. 40,41 Atherosclerosis may also affect the cerebrovasculature in HGPS. Angiographic evidence of atherosclerosis affecting both the carotid and vertebral systems 42,43 and MRI evidence of cerebral infarction [42][43][44][45] has been documented in HGPS children with localizing neurological findings.…”

Section: Atherosclerosis In Hgpsmentioning

confidence: 99%

Laminopathies and Atherosclerosis

Alshali

Hegele

2004

ATVB

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Abstract-Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. Some laminopathies affect the cardiovascular system, and a few (namely, Dunnigan-type familial partial lipodystrophy [FPLD2] and HutchinsonGilford progeria syndrome [HGPS]) feature atherosclerosis as a key component. The premature atherosclerosis of FPLD2 is probably related to characteristic proatherogenic metabolic disturbances such as dyslipidemia, hyperinsulinemia, hypertension, and diabetes. In contrast, the premature atherosclerosis of HGPS occurs with less exposure to metabolic proatherogenic traits and probably reflects the generalized process of accelerated aging in HGPS. Although some common polymorphisms of LMNA have been associated with traits related to atherosclerosis, the monogenic diseases Key Words: nuclear envelope Ⅲ insulin resistance Ⅲ aging Ⅲ vascular disease Ⅲ progeria T he nuclear lamina is a 20-nm filamentous meshwork that underlies the inner nuclear membrane and plays a central role in defining interphase nuclear architecture, DNA replication, and chromatin organization. 1 Nuclear lamins are type V intermediate filaments that are the major components of the nuclear lamina.

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Section: Atherosclerosis In Hgpsmentioning

confidence: 99%

Laminopathies and Atherosclerosis

Alshali

Hegele

2004

ATVB

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“…We frequently observed a thin calvarium, which has been noted on autopsy specimens. 9,10 The thinness of the skull bone may reflect delayed evolution of the normal bony remodeling of the skull to its mature organization, similar to stunted linear skeletal growth observed elsewhere. The normal infant skull thickens with age, transitioning from a unilaminar to a trilaminar composition.…”

Section: Calvarial and Skull Base Changesmentioning

confidence: 89%

“…However, we noted mottling of the flat bones of the skull and postulate that this finding may represent bony demineralization, similar to the juxta-articular demineralization seen on radiographs. 10,14 The osteopenia of long bones is accompanied by abnormalities in structural rigidity and is thought to represent a skeletal dysplasia, rather than the typical osteoporosis of aging. 12,20,21 Delayed closure of the anterior and posterior fontanels and widening of the calvarial sutures in HGPS have been reported.…”

Section: Calvarial and Skull Base Changesmentioning

confidence: 99%

“…8,9 Classic craniofacial features develop with age and underlying disease culminates in death from myocardial infarction or stroke at an average age of 13 years. 8,10 Close examination of common and disparate findings in HGPS and aging may inform both fields of study. Clinical features that resemble premature aging include alopecia, joint contractures, progressive mandibular resorption, low bone density, lipoatrophy with limb wasting, and global atherosclerosis.…”

mentioning

confidence: 99%

“…12 Prior reports of craniofacial features are based on plain film findings and autopsy results. 10,13,14 In this study of a large cohort of patients with HGPS, we reviewed CT, MR imaging, and radiographs to quantify previously noted and new craniofacial imaging features to expand our understanding of the natural history of the disease.…”

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confidence: 99%

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Craniofacial Abnormalities in Hutchinson-Gilford Progeria Syndrome

Ullrich

Silvera²,

Campbell

et al. 2012

AJNR Am J Neuroradiol

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SUMMARY: HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the scope of structural bone and soft-tissue craniofacial abnormalities in HGPS through CT or MR imaging. Using The Progeria Research Foundation Medical and Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age, were comprehensively reviewed. Eight newly identified abnormalities involving the calvaria, skull base, and soft tissues of the face and orbits were present with prevalences between 43% and 100%. These included J-shaped sellas, a mottled appearance and increased vascular markings of the calvaria, abnormally configured mandibular condyles, hypoplastic articular eminences, small zygomatic arches, prominent parotid glands, and optic nerve kinking. This expanded craniofacial characterization helps link disease features and improves our ability to evaluate how underlying genetic and cellular abnormalities culminate in a disease phenotype. Children with HGPS typically appear healthy at birth and within the first year of life develop severe failure to thrive with sclerodermatous skin changes. 8,9 Classic craniofacial features develop with age and underlying disease culminates in death from myocardial infarction or stroke at an average age of 13 years. 8,10 Close examination of common and disparate findings in HGPS and aging may inform both fields of study. Clinical features that resemble premature aging include alopecia, joint contractures, progressive mandibular resorption, low bone density, lipoatrophy with limb wasting, and global atherosclerosis. 8,11 Age-related conditions such as Alzheimer disease, dementia, osteoarthritis, and cancer are absent. Cognitive function and motor development are normal. In addition, there is growth failure, skeletal dysplasia, and lack of pubertal development. ABBREVIATIONS 12Prior reports of craniofacial features are based on plain film findings and autopsy results. 10,13,14 In this study of a large cohort of patients with HGPS, we reviewed CT, MR imaging, and radiographs to quantify previously noted and new craniofacial imaging features to expand our understanding of the natural history of the disease. Materials and Methods Patients and DataPatients were identified from The Progeria Research Foundation Medical and Research Database (Brown University Center for Gerontology and Healthcare Research, Providence, Rhode Island). Eligible individuals had a genetic and/or clinical diagnosis of HGPS and at least 1 MR or CT of the head or neck available for review. The diagnosis of HGPS was genetically determined by either the classic exon 11 (c. 1824 CϾT) or a nonclassic progerin-producing LMNA mutation within exon 11 or the exon/intron border, plus the typical clinical phenotype. 15Data abstraction included indications for neuroimaging studies, OFC, and medications. Height-age was determined by using the CDC and WHO child growth standards for boys and girls. 16,17 Abstracted OFC measurements from patient charts were expressed as percentiles by height-age. Neuroimaging Stu...

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On the nature of susceptibility to cancer. The presidential address

Miller

1980

Cancer

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The most prominent factor determining susceptibility to cancer is age. However, there is little evidence that the aging process per se increases susceptibility to cancer. Rather, age provides the time necessary for the accumulation of cellular events required for the development of neoplasia. The variations in the patterns of cancer incidence rates seen with age can be explained by alterations in conditions of exposure to carcinogenic stimuli. There is no evidence that the pool of susceptible individuals in a population is limited. Cancer occurs as a random event in a population with greater or lesser frequency according to the presence of risk factors. In populations with an increased frequency of cancer such as those with genetic abnormalities, immune deficiency syndromes, or altered hormonal states, the risk of developing cancer is never generalized to all tissues but is characteristic of particular tissues at risk. Any circumstance of internal or external origin that disturbs homeostasis of particular tissues at risk. Any circumstance of internal or external origin that disturbs homeostasis over a prolonged period of time increases the susceptibility to cancer for the tissue concerned. Susceptibility to cancer does not mean that cancer is inevitable. Only a small number of those susceptible to cancer by virtue of a special risk factor develop the disease. Furthermore, most patients who develop cancer have no determinable risk factors. Although all evidence points to a multifactorial, multistage process, the rate of somatic mutation appears to be the key determinant factor in susceptibility to cancer. This concept is supported by research studies showing that the onset of atherosclerosis is initiated by somatic mutations, and the finding that the same chemical mutagens can advance the development of both diseases.

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Progeria, a pathologic study

Cited by 69 publications

References 11 publications

Laminopathies and Atherosclerosis

Laminopathies and Atherosclerosis

Craniofacial Abnormalities in Hutchinson-Gilford Progeria Syndrome

On the nature of susceptibility to cancer. The presidential address

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