臨床および医療ゲノミクスジャーナル

Cytogenomic Delineation and Clinical Characterization of Three Cases of MECP2 Duplication Syndrome

Abstract

Cristelle Chow, Angeline H.M. Lai, Maggie S. Brett, Simon Ling, Jung Sook Ha, Eileen C.P. Lim, Ee-Shien Tan, and Ene-Choo Tan

The methyl-CpG-binding protein 2 gene (MECP2) on the X chromosome encodes an essential epigenetic regulator in human postnatal brain development. Increased dosage of MECP2 causes a severe syndromic form of intellectual disability, the MECP2 duplication syndrome. Males with this syndrome have a progressive neurological disorder, severe to profound intellectual disability, epilepsy and recurrent respiratory infections. We report three cases with copy number gain in Xq28 involving the MECP2 gene. The gains were detected by chromosomal microarray analysis and ranged in size from 300 kb to 4.96 Mb. The three boys were aged between 3 and 16 years old. All three had development delay and no speech. In addition, one patient was diagnosed with Lennox-Gastaut syndrome and another had a Dandy Walker variant. Their clinical features were compared with other reported cases. We concluded that all three patients’ clinical features were due to the Xq28 duplication, which confirmed the utility of chromosomal microarray analysis as a first-tier test in patients with unexplained intellectual disability. With a specific genetic diagnosis, we were able to provide appropriate anticipatory guidance for these patients and their families.