Heterozygous mutations in the PRDM5 gene (4q25-q26) are responsible for this condition. Mutations in CYP1b1, PITX2, and FOXC1 were not present. One extended pedigree with 4 affected individuals from Pakistan has been reported.
Type 1 Axenfeld-Rieger syndrome (180500) results from heterozygous mutations in PITX2, RIEG2 (601499) from heterozygous mutations in 13q14, and RIEG3 (602482) from heterozygous mutations in the FOXC1 gene. Thus in three types of Axenfeld-Rieger syndrome (1,3, and 4) the responsible mutation occurs in a transcription factor gene which may explain why the phenotype is highly variable with considerable overlap in clinical signs.
Autosomal recessive brittle cornea syndrome type 2 (614170) is also caused by mutations in the PRDM5 gene.