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The syndromes associated with an accelerated or premature aging (often called progeroid) phenotype represent an uncommon but medically and biologically important class of disorders. These conditions are characterized by physical manifestations that produce a prematurely aged appearance or symptoms suggesting accelerated aging unexpected for a child or adolescent. Although one of these conditions, Hutchinson-Gilford progeria (HGP), is the prototype for this community of diseases, there are at least 20 human syndromes that have been labeled as progeroid. It is a common mistake for both the clinician and the media to incorrectly lump all of these disorders under the heading of progeria, even though there are several discrete entities. Making an accurate diagnosis of the correct accelerated/premature aging syndrome is crucial because all of these conditions vary in inheritance pattern, natural history and prognosis. The plan of management and health care supervision is informed by the diagnosis here, as is the case of all genetic syndromes.

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Table 184-1 (modified from a recent commentary by Neilan in 20091) classifies the commonly described progeroid syndromes by the pathogenetic category of the disorder. Hutchinson-Gilford progeria, the mandibuloacral dysplasias (MAD), and the connective tissue dysplasias with signs of premature aging will be discussed in more detail in subsequent section. Table 184-1 provides a listing of clinical manifestations of the conditions, as well as the inheritance pattern and the gene locus, gene name, and encoded protein if known. Of note, different mutations of the gene LAMA cause multiple different phenotypes, including HGP and a form of MAD as well as several nonclassical progeroid phenotypes1-3 displaying the genetic principle of allelic heterogeneity. It is also interesting that MAD is genetically heterogeneous (locus heterogeneity) and can be caused by mutations of LAMA or the gene ZMPSTE24, which encodes a peptide that is involved in the posttranslational modification of lamin A/C.4

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Table Graphic Jump Location
Table 184-1. Syndromes with an Accelerated Aging (Progeroid) Phenotype

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