The 12q14 microdeletion syndrome; 6 new cases confirming the role of HMGA2 in growth

ABSTRACT We report 6 patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations performed on children with developmental delay and dysmorphism in 3 diagnostic testing centres; 6 positive cases gives a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions which included HMGA2 and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects including 2 with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay, and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.