ZNF462相关综合征的表型描述.

Zinc finger protein 462 (ZNF462) is a relatively newly discovered
vertebrate specific protein with known critical roles in embryonic
development in animal models. Two case reports and a case series study have
described the phenotype of 10 individuals with ZNF462 loss of function
variants. Herein, we present 14 new individuals with loss of function
variants to the previous studies to delineate the syndrome of loss of
function in ZNF462. 集体, these 24 individuals present with
recurring phenotypes that define a multiple congenital anomaly syndrome.
Most have some form of developmental delay (79%) and a minority has autism
spectrum disorder (33%). Characteristic facial features include ptosis
(83%), down slanting palpebral fissures (58%), exaggerated Cupid’s bow/wide
philtrum (54%), and arched eyebrows (50%). Metopic ridging or
craniosynostosis was found in a third of study participants and feeding
problems in half. Other phenotype characteristics include dysgenesis of the
corpus callosum in 25% of individuals, hypotonia in half, and structural
heart defects in 21%. Using facial analysis technology, a computer
algorithm applying deep learning was able to accurately differentiate
individuals with ZNF462 loss of function variants from individuals with
Noonan syndrome and healthy controls. In summary, we describe a multiple
congenital anomaly syndrome associated with haploinsufficiency of ZNF462
that has distinct clinical characteristics and facial features.