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Only six MAD patients are reported so far with <jats:italic>ZMPSTE24<\/jats:italic> mutations and limited phenotypic data are available for them. Here, we report on two brothers (4 years and 9\u2010month old) with early onset MAD due to <jats:italic>ZMPSTE24<\/jats:italic> mutations in whom thin skin was noted as early as 5 months of age. Both had micrognathia, mottled hyperpigmentation, and enlarged fontanelles but little evidence of lipodystrophy. There was no delay of mental development. The older brother had small pinched nose, short clavicles, acro\u2010osteolysis, stunted growth, joint stiffness, and repeated fractures. There was no evidence of renal disease. Both patients were compound heterozygotes harboring a previously reported missense <jats:italic>ZMPSTE24<\/jats:italic> mutation, p.Pro248Leu, and a novel null mutation, p.Trp450stop. These patients and the review of literature reveal that compared to MAD patients with <jats:italic>LMNA<\/jats:italic> mutations, those with <jats:italic>ZMPSTE24<\/jats:italic> mutations develop manifestations earlier in life. Other distinguishing features in MAD due to <jats:italic>ZMPSTE24<\/jats:italic> mutations may include premature birth, renal disease, calcified skin nodules, and lack of acanthosis nigricans. We conclude that in patients with MAD due to <jats:italic>ZMPSTE24<\/jats:italic> mutations, the onset of disease manifestations such as thin skin and micrognathia occurs as early as 5 months of age. In these patients, skeletal phenotype presents earlier whereas lipodystrophy and renal disease may occur later in life. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33664","type":"journal-article","created":{"date-parts":[[2010,9,3]],"date-time":"2010-09-03T17:44:31Z","timestamp":1283535871000},"page":"2703-2710","source":"Crossref","is-referenced-by-count":51,"title":["Early onset mandibuloacral dysplasia due to compound heterozygous mutations in 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