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A sporadic syndrome of premature aging with
characteristic facies, severe cardiac lesions (including myocardial
infarction), and various orthopedic and otorhinolaryngologic lesions.
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Hutchinson-Gilford Progeria Syndrome; Gilford Syndrome;
Premature Senility Syndrome.
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Rare genetic disease characterized by premature aging.
First described by Jonathan Hutchinson in 1886.
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Sporadic cases. Fewer than 100 cases reported in the
literature. Progeria affects between 1:4 million (estimated actual) and 1:8
million (reported) live births.
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In most patients, the syndrome is caused by
random genetic changes occurring for unknown reasons. Because it occurs
sporadically, it is believed to be an autosomal recessive disorder. However,
these mutations might be transmitted as an autosomal dominant trait.
Male:female ratio is 1.5:1. Whites account for 97% of all reported cases.
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A reduction in the amount of cell DNA repair
activity has been demonstrated and postulated as a cause of the premature
aging. The genes controlling cell division and DNA or RNA synthesis and
processing commonly are downregulated in elderly people and in progeria (15
genes involved). This suggests that abnormal regulation of the separation of
the chromosomes during cell division occurs. There are characteristic
changes in expression of actin-binding proteins (caldesmons), which are involved in
cell cycle-dependent reorganization of the cytoskeleton, desmoplakin I, which
plays a role in intercellular adhesive junctions, and autotaxins, which are
involved in cellular chemotaxis. On the other hand, transforming growth factor-β
(TGF-β) is highly upregulated in patients with progeria, thus
yielding tissue fibrosis.
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No firm diagnostic criteria have been described in
patients with premature aging of postnatal onset, including characteristic
facies, musculoskeletal abnormalities, and early death caused by
atherosclerosis and/or myocardial ischemia.
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Clinical manifestations are evident by the first
or second year of life. The appearance includes facial hypoplasia with
micrognathia, thin skin, alopecia, dental late eruption, ophthalmic
abnormality (microphthalmia, exophthalmia, cataract), ear abnormality
(hypoplastic lobe, conductive hearing loss), and a high-pitched voice.
Cardiovascular lesions are severe and frequent, characterized by a
progressive atherosclerosis (coronary, aortic, and cerebral artery).
Hypertension, myocardial infarction, or congenital heart failure often cause
premature death. There is no mental retardation. Orthopedic modifications
are numerous: hip dislocation, early osteoporosis, dwarfism, restricted
joint mobility, clavicle anomalies, and large fontanel. Hypoplastic toe
nails are frequent. Hypogonadism and diabetes can be observed.
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Obtain full personal history to find
existence of symptomatic vascular or CNS ...