Syndrome of the Month: Van den Ende-Gupta Syndrome: Gestalt Diagnosis, Outcomes, and Recommendations

Van den Ende-Gupta syndrome (VDEGS) is an autosomal recessive disorder involving self-resolving joint contractures that are present since birth. Because of characteristic facial features, clinical diagnosis may be suspected by experienced clinicians or identified using facial recognition-based software. Confirmation by identification of disease-causing biallelic variants in SCARF2 can be helpful to definitively provide a clinico-molecular diagnosis to differentiate VDEGS from other disorders with overlapping phenotypes with blepharophimosis, arachnodactyly, and camptodactyly. Most affected individuals do not have major malformations or intellectual disability. However, occasional patients with ophthalmological, genitourinary, or laryngeal abnormalities are reported, indicating the need for a detailed evaluation. The causative gene, SCARF2, is located within the region of the 22q11.2 microdeletion syndrome. Two cases with microdeletion of the region on one chromosome and a SCARF2 variant on the other chromosome have been reported. Two cases resembling the phenotype but with no causative variants in SCARF2 have been reported, supporting the possibility of another causative gene with overlapping phenotype. Though prognosis can often be positive, there is a need for better long-term outcome data.