Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics

Liebenberg syndrome (MIM 186550) is a very rare autosomal dominant condition characterized by three main features: dysplasia of all of the bony components of the elbow joint, abnormalities in the shape of carpal bones, and brachydactyly. In this paper, we report a Saudi Arabian family with Liebenberg syndrome. Comparative genomic hybridization (CGH) revealed a 275-kb deletion within the cytogenetic band 5q31.1 which contains the H2AFY gene and 190,428 bp of its downstream region. The deleted region is upstream to the PITX1 gene. The radiological features in the upper limbs of all affected members of the family were almost identical to the phenotype in the mouse model with ectopic expression of Pitx1 in the forelimbs. We therefore re-define the phenotype of Liebenberg syndrome as a transformation of the upper limbs to reflect lower limb characteristics and speculate that the area of deletion contains a regulatory sequence that suppresses the expression of PITX1 in the upper limb buds.