Lysine methyltransferase 2D (KMT2D; OMIM 602113) encodes a histone 
methyltransferase involved in transcriptional regulation of the beta-globin and 
estrogen receptor as part of a large protein complex known as activating signal 
cointegrator-2-containing complex (ASCOM). Heterozygous germline mutations in 
the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental 
multisystem disorder. Neither holoprosencephaly nor other defects in human 
forebrain development have been previously associated with Kabuki syndrome. Here 
we report two patients diagnosed with alobar holoprosencephaly in their 
antenatal period with de novo monoallelic KMT2D variants identified by 
trio-based exome sequencing. The first patient was found to have a stop-gain 
variant c.12565G>T (p.Gly4189*), while the second patient had a missense variant 
c.5A>G (p.Asp2Gly). Phenotyping of each patient did not reveal any age-related 
feature of Kabuki syndrome. These two cases represent the first report on 
association between KMT2D and holoprosencephaly.