Redefining the MED13L syndrome

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.
We thank all families for participation in this study, Bettina Lipkowitz and Susanne Freier for excellent technical assistance. This work was supported by the Deutsches Humangenom-Programm (DHGP, grant number 01KW9908), the Nationales Genomforschungsnetzwerk (NGFN, project number 01GR0105), the German Research Foundation (SFB665), the Brain and Behavior Foundation (AA), the Berlin Institute of Health (BIH), the Sonnenfeld Stiftung, the Senate of Berlin by funds to the Berlin Institute for Medical Systems Biology (BIMSB), the Iranian National Science foundation, FEDER funds through the COMPETE program, Portuguese national funds through FCT - Fundacao para a Ciencia e Tecnologia (project PIC/IC/83026/2007, scholarship to FL SFRH/BD/84650/2010), the Max Planck Society and the EU FP 7 project GENCODYS (grant number 241995).