The First Reported Case of an Inherited Pathogenic Variant in DEAF1 From a Parent With Milder Phenotype Provides Evidence of Variable Gene Expressivity of the DEAF1-Associated Vulto-van Silfout-de Vries Syndrome (VSVS)

DEAF1-associated neurodevelopmental disorder (DAND) is a neurodevelopmental spectrum disorder caused by two methods of inheritance: the autosomal dominant intellectual disability syndrome (Vulto-van Silfout-de Vries syndrome (VSVS), OMIM #615828), and the autosomal recessive Neurodevelopmental disorder with hypotonia and impaired expressive language with or without seizures (NEDHELS OMIM #615828) (OMIM 617171). All reported cases of VSVS have occurred de novo. In this report, we describe the case of a 2-year-old male with a history of autism spectrum disorder and behavioral concerns who was identified to be heterozygous for the c.837C>G (p.C279W) pathogenic variant in DEAF1. Functional assays demonstrate that the p.C279W variant alters DEAF1's transcriptional repression activity. This variant was also identified in his 26-year-old mother, who also has a history of autism and speech delay. To the best of our knowledge, this is the first reported case of the dominant form of DEAF1-associated neurodevelopmental disorder inherited from an affected parent.