Investigation of the 22q11.2 candidate region in patients with midline facial defects with hypertelorism.

Midline facial defects with hypertelorism (MFDH) are mainly characterized by ocular hypertelorism and bifid nose. They are often associated with structural and functional anomalies of the central nervous system similar to those found in 22q11.2 deletion syndromes. In addition, there are some isolated reports of MFDH and 22q11.2 deletion. These findings suggest that MFDH may be part of the spectrum of 22q11.2 deletion syndromes. To test this hypothesis, 10 individuals with MFDH were analyzed by fluorescent in situ hybridization (FISH), but no 22q11.2 deletion was detected. In view of this result, the TBX1 gene located within the 22q11.2 candidate region was screened. A new sequence variant (1132GA) was identified in one patient. This variant was not found in 110 control individuals genotyped. Considering the rarity of this condition and results of this study, the involvement of the 22q11.2 chromosomal region in the pathogenesis of MFDH could not be excluded.