Ohdo syndrome comprises a heterogeneous group of disorders characterized by 
intellectual disability (ID) and typical facial features, including 
blepharophimosis. Clinically, these blepharophimosis-ID syndromes have been 
classified in five distinct subgroups, including the Maat-Kievit-Brunner (MKB) 
type, which, in contrast to the others, is characterized by X-linked inheritance 
and facial coarsening at older age. We performed exome sequencing in two 
families, each with two affected males with Ohdo syndrome MKB type. In the two 
families, MED12 missense mutations (c.3443G>A [p.Arg1148His] or c.3493T>C 
[p.Ser1165Pro]) segregating with the phenotype were identified. Upon subsequent 
analysis of an additional cohort of nine simplex male individuals with Ohdo 
syndrome, one additional de novo missense change (c.5185C>A [p.His1729Asn]) in 
MED12 was detected. The occurrence of three different hemizygous missense 
mutations in three unrelated families affected by Ohdo syndrome MKB type shows 
that mutations in MED12 are the underlying cause of this X-linked form of Ohdo 
syndrome. Together with the recently described KAT6B mutations resulting in Ohdo 
syndrome Say/Barber/Biesecker/Young/Simpson type, our findings point to aberrant 
chromatin modification as being central to the pathogenesis of Ohdo syndrome.