Syndromes with Premature Ageing
Syndromes associated with premature ageing comprise a clinically and genetically heterogeneous group of disorders. Werner syndrome and Bloom syndrome both arise due to DNA helicase gene mutations resulting in growth deficiency and a predisposition to malignancy, amongst other features. Another mechanism of premature ageing arises in the progeroid laminopathies whereby aberrant lamin A processing leads to the accumulation of progerin in the cell nucleus, variably causing severe growth retardation, accelerated ageing, skeletal abnormalities and early death from cardiovascular disease. The cutis laxa syndromes result from mutations in genes involved in the formation or modification of elastic fibres, giving rise clinically to lax skin in addition to gastrointestinal, genito‐urinary, vascular or pulmonary compromise. The association of premature ageing syndromes with significant and severe systemic features highlights the need for accurate clinical and molecular characterization of affected individuals.
Keywords premature ageing, Werner syndrome, Bloom syndrome, laminopathy, lamin A/C, Hutchinson–Gilford progeria, mandibulo‐acral dysplasia with lipodystrophy, cutis laxa, elastin, fibulin