Progeria is a rare syndrome of accelerated aging that manifests early in childhood and causes premature death.
Progeria, also known as Hutchinson-Gilford syndrome, is a rare genetic condition that causes children to age rapidly, leading to premature aging symptoms and a shortened lifespan.
Progeria is caused by a sporadic mutation in the LMNA gene that codes for a protein (lamin A) that provides the molecular scaffolding of cell nuclei. The defective protein leads to nuclear instability from cell division and early death of every body cell.
Mean survival is 14.6 years of age; the cause is typically coronary artery and cerebrovascular disease (1). Insulin resistance and atherosclerosis may develop. Of note is that other problems associated with normal aging (eg, increased cancer risk, degenerative arthritis) are not present.
Symptoms and signs of progeria develop within 2 years of birth and include:
Growth failure (eg, short stature, delayed tooth eruption)
Craniofacial abnormalities (eg, craniofacial disproportion, micrognathia, beaked nose, macrocephaly, large fontanelle)
Physical changes of aging (eg, wrinkled skin, balding, decreased range of motion of joints, tough skin that resembles scleroderma)
Diagnosis of progeria is usually obvious by appearance but must be distinguished from segmental progerias (eg, acrogeria, metageria) and other causes of growth failure.
Lonafarnib is an oral medication that prevents defective progerin or progerin-like protein build-up. A multicenter prospective cohort study showed it lowers mortality (3.7% vs 33.3%) compared to placebo after 2.2 years of follow-up (Lonafarnib is an oral medication that prevents defective progerin or progerin-like protein build-up. A multicenter prospective cohort study showed it lowers mortality (3.7% vs 33.3%) compared to placebo after 2.2 years of follow-up (2).
Support groups are available.
Other progeroid syndromes
Premature aging is a feature of other rare progeroid syndromes.
Werner syndrome is premature aging after puberty with hair thinning and development of conditions of old age (eg, cataracts, diabetes, osteoporosis, atherosclerosis). Rothmund-Thomson syndrome is 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 disorder 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 intellectual disability.
Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome) is a recessively inherited syndrome of aging causing death by age 2 years.
Other syndromes (eg, Down, Ehlers-Danlos) occasionally have progeroid features.
References
1. Gordon LB, Massaro J, D'Agostino RB Sr, et al. Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation. 2014;130(1):27-34. doi:10.1161/CIRCULATIONAHA.113.008285
2. Gordon LB, Shappell H, Massaro J, et al. Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome. JAMA. 2018;319(16):1687-1695. doi:10.1001/jama.2018.3264
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