2q31.1 microdeletion syndrome- redefining the associated clinical phenotype

Boyan I Dimitrov (1) , Irina Balikova (1) , Thomy de Ravel (1) , Hilde van Esch (1) , Maryse de Smedt (2) , Emiel Baten (3) , Joris R Vermeesch (1) , Irena Bradinova (4) , Emil Simeonov (5) , Koen Devriendt (1) , Jean-Pierre Fryns (1) , Philippe Debeer (6)

1 Centre for Human Genetics
2 AZ Sint-Augustinus, 2610 Wilrijk
3 Sint Lucas Hospital, 8310 Bruges
4 University Hospital Aleksandrovska, Department of Paediatrics, Medical University Sofia, 1431 Sofia
5 University Hospital Aleksandrovska, Department of Paediatrics, Medical University Sofia, 1431 Sofia
6 Department of Musculoskeletal Science, Division of Orthopedics, University Hospitals, K.U. Leuven

Introduction: The clinical phenotype of the chromosome 2q31 deletion syndrome consists of limb anomalies ranging from monodactylous ectrodactyly, brachydactyly and syndactyly to camptodactyly. Additional internal organ anomalies, e.g. heart defects, ocular anomalies may be present. Hemizygosity for HOXD13 and EVX2 genes was thought to cause the observed skeletal defects. Recently, based on the phenotype of patients with overlapping 2q31 interstitial deletions, a new SHFM5 locus was proposed- proximal to the HOXD cluster, between EVX2 and marker D2S294. DLX1 and DLX2 haploinsufficiency was suggested as the most plausible explanation for the observed SHFM-like limb anomalies in these cases. Methods and Results: Five unique, interstitial 2q31 deletion patients were selected to further characterize the 2q31 region and to establish a genotype/phenotype correlation map. The size of the deletions was delineated with a chromosome 2 specific tiling path BAC array. The clinical and molecular data for this group of patients were compared to others in the literature. A common locus for the observed skeletal anomalies, including the HOXD genes and surrounding regulatory sequences, was delineated. These results correlate with recently published studies in animal models. In addition, a critical region for the facial gestalt of the 2q31.1 microdeletion syndrome was delineated. Conclusions: Our results reinforce the hypothesis that the variable skeletal phenotype in 2q31 deletion patients is a result of hemizygosity for the HOXD genes and that the 2q31.1 microdeletion syndrome is a well defined and clinically recognizable phenotype.

Mots clés: Genetics; Clinical genetics; Cytogenetics; Genetic screening/counselling; Molecular genetics

Boyan I Dimitrov, Irina Balikova, Thomy de Ravel, Hilde van Esch, Maryse de Smedt, et al.. 2q31.1 microdeletion syndrome- redefining the associated clinical phenotype. Journal of Medical Genetics, 2010, 48 (2), pp.98. ⟨10.1136/jmg.2010.079491⟩. ⟨hal-00584725⟩