The most common characteristics include a distinct craniofacial phenotype (microcephaly, micrognathia, short philtrum, prominent glabella, ocular hypertelorism, dysplastic ears and periauricular tags), growth restriction, intellectual disability, muscle hypotonia, seizures, and congenital heart defects.

[7] The phenotypic characteristics of WHS are thought to be caused by the haploinsufficiency of the genes Wolf-Hirschhorn syndrome candidate 1 (WHSC1), which is associated with craniofacial features and growth delay, and Homo Sapiens leucine zipper-EF-hand containing transmembrane protein 1 (LETM1), which is associated with seizures.

[9] Severity of symptoms and expressed phenotype differ based on the amount of genetic material deleted.

The critical region for determining the phenotype is at 4p16.3 and can often be detected through genetic testing and fluorescence in situ hybridization (FISH).

Some treatment methods are surgery for growth abnormalities, educational programs that can help with cognition, physical therapy for muscle building, and medication for seizures.