Phenotypic variability in patients with interstitial 6q21-q22 microdeletion and Acro–Cardio–Facial syndrome

Deletions of 6q are known to be associated with variable clinical phenotypes including facial dysmorphism, hand malformations, heart defects, microcephaly, intellectual disability, epilepsy, and other neurodevelopmental and neuropsychiatric conditions. Here, we report a 7-year-old boy evaluated for facial dysmorphism, trigonocephaly, microcephaly, global developmental delay, and behavioral abnormalities. Molecular karyotyping revealed a 13-Mb deletion within 6q21-q22.31, (chr6:105,771,520-119,130,805; hg19, GRch37) comprising 81 genes. Review of 15 cases with interstitial 6q21-q22.3 deletion from the literature showed that facial dysmorphism, intellectual disability, and corpus callosum abnormalities are the most consistent clinical features in these individuals. Deleted genes and breakpoints in the 6q21-q22 region of the patient reported here are similar to two earlier reported cases with the clinical diagnosis of Acro–Cardio–Facial syndrome. However, the present case lacks characteristic clinical findings of Acro–Cardio–Facial syndrome. We discuss, the considerable phenotypic variability seen in individuals with 6q21-q22 microdeletion and emphasize the need for further scrutiny into the hypothesis of Acro–Cardio–Facial syndrome being a microdeletion syndrome.