Skeletal Dysplasia_Fetal

Gene: DVL1

Green List (high evidence)

Previous review by Belinda Chong:

Onset at birth - Robinow syndrome is a skeletal dysplasia characterized by distinctive facial features, including midface hypoplasia, hypertelorism, a short nose, and a broad mouth, known collectively as 'fetal facies.' Additional features include mesomelic dwarfism, macrocephaly, gingival hypertrophy, dental malocclusion, genital hypoplasia, and brachydactyly . Additionally, increased skull bone density and appendicular osteosclerosis are present in patients with DRS2.

Only variants that result in truncation (located in the final 2 exons) have been reported as pathogenic. Pathogenic truncating variants that escape NMD have been shown to result in a gain of function with increased canonical WNT activity. The paternal allele is predicted to be imprinted, with the maternal allele expressed (geneimprint.com) however reports so far have been for de novo variants.
Sources: Literature

Created: 25 Oct 2022, 6:09 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
Robinow syndrome, autosomal dominant 2 (MIM#616331)

Publications

• 25817014
• 25817016

Variants in this GENE are reported as part of current diagnostic practice