22q11.2 distal deletion syndrome is distinct from the common 22q11.2 deletion syndrome and caused by microdeletions localized adjacent to the common 22q11 deletion at its telomeric end. Most distal deletions of 22q11 extend from LCR22-4 to an LCR in the range LCR22-5 to LCR22-8. We present three patients with 22q11 distal deletions, of whom two have complex congenital heart malformation, thus broadening the phenotypic spectrum. We compare cardiac malformations reported in 22q11 distal deletion to those reported in the common 22q11 deletion syndrome. We also review the literature for patients with 22q11 distal deletions, and discuss the possible roles of haploinsufficiency of the MAPK1 gene. We find the most frequent features in 22q11 distal deletion to be developmental delay or learning disability, short stature, microcephalus, premature birth with low birth weight, and congenital heart malformation ranging from minor anomalies to complex malformations. Behavioral problems are also seen in a substantial portion of patients. The following dysmorphic features are relatively common: smooth philtrum, abnormally structured ears, cleft palate/bifid uvula, micro-/retrognathia, upslanting palpebral fissures, thin upper lip, and ear tags. Very distal deletions including region LCR22-6 to LCR22-7 encompassing the SMARCB1-gene are associated with an increased risk of malignant rhabdoid tumors.
European Journal of Medical Genetics, 2013, Vol 56, Issue 2, p. 98-107