Ventricular noncompaction and absent thumbs in a newborn with tetrasomy 5q35.2-5q35.3: an association with Hunter-McAlpine syndrome?

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Ohio, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.3). 06/2011; 155A(6):1409-13. DOI: 10.1002/ajmg.a.33997
Source: PubMed

ABSTRACT We report on an infant with tetrasomy of 5q35.2-5q35.3, an interstitial triplication on one chromosome and normal complement on the other. The patient has some features of Hunter-McAlpine syndrome including intrauterine growth retardation (IUGR), almond-shaped eyes, epicanthal folds, and downturned mouth with thin vermillion of the upper lip. In addition, left ventricular noncompaction and absent thumbs were identified, which have never been described in Hunter-McAlpine syndrome. This chromosome abnormality is distinct from those previously reported. Within this region of tetrasomy is MSX2, a highly conserved homeobox containing gene. Increased copies of MSX2 have been previously associated with craniosynostosis. Our patient's only skeletal defect is absent thumbs, also potentially related to increased dosage of MSX2 which is important for limb formation. In addition, MSX2 is expressed in the developing heart and overexpression of this gene may disrupt the co-regulation of other cardiac genes in this region, namely CSX1.

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