Severe Developmental Delay in a Patient with 7p21.1-p14.3 Microdeletion Spanning the TWIST Gene and the HOXA Gene Cluster

H Fryssira; P Makrythanasis; A Kattamis; K Stokidis; B Menten; K Kosaki; P Willems; E Kanavakis

doi:10.1159/000334313

Severe Developmental Delay in a Patient with 7p21.1-p14.3 Microdeletion Spanning the TWIST Gene and the HOXA Gene Cluster

Mol Syndromol. 2011 Dec;2(1):45-49. doi: 10.1159/000334313. Epub 2011 Nov 12.

Authors

H Fryssira¹, P Makrythanasis, A Kattamis, K Stokidis, B Menten, K Kosaki, P Willems, E Kanavakis

Affiliation

¹ Department of Medical Genetics, University of Athens Medical School, Choremio Research Laboratory, 'Aghia Sophia' Children's Hospital, Athens, Greece.

Abstract

We describe a patient with a rare interstitial deletion of chromosome 7p21.1-p14.3 detected by array-CGH. The deletion encompassed 74 genes and caused haploinsufficiency (or loss of allele) of 6 genes known to be implicated in different autosomal dominant genetic disorders: TWIST, DFNA5, CYCS, HOXA11, HOXA13, and GARS. The patient had several morphological abnormalities similar to Saethre-Chotzen syndrome (caused by TWIST mutations) including craniosynostosis of the coronal suture and anomalies similar to those seen in hand-foot-uterus syndrome (caused by HOXA13 mutations) including hypospadias. The combined phenotype of Saethre-Chotzen syndrome and hand-foot-uterus syndrome of our patient closely resembles a previously reported case with a cytogenetically visible small deletion spanning 7p21-p14.3. We therefore conclude that microdeletions of 7p spanning the TWIST gene and HOXA gene cluster lead to a clinically recognizable 'haploinsufficiency syndrome'.