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Early onset mandibuloacral dysplasia due to compound heterozygous mutations in ZMPSTE24
Author(s) -
Ahmad Zahid,
Zackai Elaine,
Medne Livija,
Garg Abhimanyu
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33664
Subject(s) - progeria , compound heterozygosity , missense mutation , lmna , premature aging , medicine , dysplasia , lipodystrophy , endocrinology , mutation , pathology , genetics , biology , gene , antiretroviral therapy , viral load , virus
Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by hypoplasia of the mandible and clavicles, acro‐osteolysis, and lipodystrophy due to mutations in LMNA or ZMPSTE24 . Only six MAD patients are reported so far with ZMPSTE24 mutations and limited phenotypic data are available for them. Here, we report on two brothers (4 years and 9‐month old) with early onset MAD due to ZMPSTE24 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‐osteolysis, stunted growth, joint stiffness, and repeated fractures. There was no evidence of renal disease. Both patients were compound heterozygotes harboring a previously reported missense ZMPSTE24 mutation, p.Pro248Leu, and a novel null mutation, p.Trp450stop. These patients and the review of literature reveal that compared to MAD patients with LMNA mutations, those with ZMPSTE24 mutations develop manifestations earlier in life. Other distinguishing features in MAD due to ZMPSTE24 mutations may include premature birth, renal disease, calcified skin nodules, and lack of acanthosis nigricans. We conclude that in patients with MAD due to ZMPSTE24 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. © 2010 Wiley‐Liss, Inc.