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Progeria
is a rare syndrome of accelerated aging that manifests early in
childhood and causes premature death.
Progeria
is caused by a sporadic mutation in the LMNA gene that
codes for a protein (lamin A) which provides the molecular
scaffolding of cell nuclei. Defective protein leads to nuclear
instability from cell division and early death of every body cell.
Symptoms
and signs develop within 2 yr and include growth failure,
craniofacial abnormalities (eg, craniofacial disproportion,
micrognathia, beaked nose), and physical changes of aging (eg,
wrinkled skin, balding). Diagnosis is usually obvious by
appearance but must be distinguished from segmental progerias (eg,
acrogeria, metageria) and other causes of growth failure. Median
age at death is 12 yr; cause is coronary artery and
cerebrovascular disease. Of note is that other problems associated
with normal aging (eg, increased cancer risk, degenerative
arthritis) are not present. There is no known treatment.
Premature
aging is a feature of other rare progeroid syndromes, including
Werner's syndrome (premature aging after puberty with hair
thinning and development of conditions of old age [eg, cataracts,
diabetes, osteoporosis, atherosclerosis]) and Rothmund-Thomson
syndrome (premature aging with increased susceptibility to
cancer). Both are caused by gene mutations leading to defective
RecQ DNA helicases, which normally repair DNA. Cockayne syndrome
is an autosomal recessive disease caused by mutation in the ERCC8
gene, which is important in DNA excision repair. Clinical features
include severe growth failure, cachectic appearance, retinopathy,
hypertension, renal failure, skin photosensitivity, and mental
retardation. Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome
is a recessively inherited syndrome of aging causing death by 2
yr. Other syndromes (eg, Down, Ehlers-Danlos) occasionally have
progeroid features.
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