Gabriele-De Vries syndrome is molecularly defined by the presence of pathogenic loss-of-function mutations in YY1 gene on chromosome 14, consistent with an autosomal dominant inheritance pattern. All individuals reported to date present the disorder as a result of a de novo mutation in YY1.
Individuals with deletions of YY1 may present with similar phenotypes although the phenotypic spectrum and severity, including the degree of developmental delay as well as the presence of congenital malformations, may be confounded by the concurrent deletion of other genes.
YY1 encodes Yin and yang 1 (YY1), a zinc-finger transcription factor (TF). The dual function inscribed in its name has been extended to a large number of genes and cell types and further articulated through an additional partitioning of YY1 activity between Polycomb-associated and independent functions.
Molecular confirmation is necessary for a definitive diagnosis. Most of the affected individuals have been diagnosed through whole exome sequencing, perhaps due to the relatively unspecific facial and general clinical findings. Targeted Sanger sequencing can also be used for the detection of pathogenic variants when the phenotype is suggestive, as well as the presence of a variant that has previously been identified in other affected family members.
Prenatal testing may be considered for pregnancies at increased risk, in families in which the pathogenic mutation has been identified.