Published on 25/03/2015 by admin
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Chapter 84 Progeria
Michael J. Painter
The Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal, sporadic, autosomal dominant disorder with an incidence of ≈1/4,000,000 live births. HGPS is regarded as the most prominent of the senile-like appearance syndromes. Sexual maturation is incomplete and these patients do not reproduce. Parent to child transmission has not occurred. The most prominent features of HGPS are changes that simulate accelerated aging, the recognition of which establishes the diagnosis. Genetic diagnosis is available; HGPS is caused by a single base mutation in LMNA, which results in the production of a mutant lamin A, progerin. Progerin is found in increased concentration in fibroblasts of normal older compared to younger individuals, suggesting a role in normal aging. The mean age of survival of children with HGPS is 13 yr, with a range of 5 to 20 yr, such that there are approximately 40 patients world wide at any point in time. A study of 15 patients, about 40% of the world’s population, revealed that all were heterozygous for the G608G mutation.
Children with progeria usually appear normal at birth, but occasionally, findings such as circumoral cyanosis, pinched nose, and tight skin suggest the diagnosis. Shortly after birth profound changes in growth parameters, skin, hair, dentition, ophthalmologic status, hearing, bone development, and blood vessels occur.
Birthweight is normal, but by 2 mo of age, weight is below the 3rd percentile. Between 2 and 10 yr of age, normal children gain 1.80 kg/yr whereas children with HGPS gain 0.44 to 0.65 kg/yr. Linear growth, while severely retarded, is less affected than weight. Height falls below the 3rd percentile at the age of 16 mo; because the majority of children with HGPS have developed knee contractures by that time, height measurements are probably an underestimate. The disparity of weight and height delay, associated with the loss of subcutaneous fat, results in the emaciated appearance characteristic of HGPS. These abnormalities of growth cannot be accounted for by inadequate caloric intake. Growth hormone is normal, and insulin resistance is usually only mild. Abnormalities in skin development result in thin, taut, pigmented skin with prominent veins and scleroderma-like changes. Alopecia, loss of eyebrows and eyelashes, and diminution of subcutaneous fat, including earlobes, are characteristic.
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