Progeria Syndrome

At a glance

A sporadic laminopathy of premature aging with characteristic facies, severe cardiac lesions (including myocardial infarction), and various orthopedic and otorhinolaryngologic lesions.

Synonyms

Hutchinson-Gilford Progeria Syndrome; Hutchinson-Gilford Syndrome; Gilford Syndrome; Premature Senility Syndrome.

History

First described by English surgeon and pathologist Sir Jonathan Hutchinson in 1886.

Incidence

Sporadic cases. Progeria affects between 1 in 4 million (estimated actual) and 1 in 8 million (reported) live births. Fewer than 500 patients reported.

Genetic inheritance

Sporadic or autosomal dominant transmission. Male/female ratio is 1.5:1. Caucasians account for 97% of all reported cases. Most patients do not survive long enough to reproduce.

Pathophysiology

Progeria is caused by de novo heterozygous mutation in the lamin A gene (LMNA) on chromosome 1q22 which encodes for prelamin A. Mutations in the integral membrane zinc metalloprotease gene ZMPSTE24 (critical for the final step in the biogenesis of the nuclear scaffold protein) have also been reported. Lamin A is a structural protein of the inner membrane of the cell nucleus. The progerin isoform of lamin A accumulates in and causes thickening of the nuclear membrane due to persistent farnesylation leading to cell damage.

Diagnosis

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.

Clinical aspects

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 at an average age of 14.6 years. 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. Lonafarnib, a farnesyltransferase enzyme inhibitor, has been used to reduce mortality in progeria.

Precautions before anesthesia

Obtain full personal history to find existence of symptomatic vascular or central nervous system (CNS) disorders. Cardiovascular evaluation is needed (ECG, chest radiograph, echography, coronarography, and even radionuclide imaging to eliminate the possibility of advanced ischemic disease). Evaluate tracheal intubation conditions by cautious clinical examination and radiography. Evaluate the extent of osteoporosis and diabetes.