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2q31.1 microdeletion syndrome: redefining the associated clinical phenotype
  1. Boyan Dimitrov1,
  2. Irina Balikova1,
  3. Thomy de Ravel1,
  4. Hilde Van Esch1,
  5. Maryse De Smedt1,2,
  6. Emiel Baten3,
  7. Joris Robert Vermeesch1,
  8. Irena Bradinova4,
  9. Emil Simeonov4,
  10. Koen Devriendt1,
  11. Jean-Pierre Fryns1,
  12. Philippe Debeer1,5
  1. 1Centre for Human Genetics, University Hospitals, Leuven, Belgium
  2. 2AZ Sint-Augustinus, Wilrijk, Belgium
  3. 3Sint Lucas Hospital, Bruges, Belgium
  4. 4Department of Paediatrics, University Hospital Aleksandrovska, Medical University Sofia, Sofia, Bulgaria
  5. 5Department of Musculoskeletal Science, Division of Orthopedics, University Hospitals, Pellenberg, Belgium
  1. Correspondence to Dr Philippe Debeer, Centre for Human Genetics, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; philippe.debeer{at}


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—for example, 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 characterise 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 bacterial artificial chromosome (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 These 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 recognisable phenotype.

  • HOXD13
  • synpolydactyly
  • limb defects
  • 2q31.1 deletion syndrome
  • genetics
  • clinical genetics
  • cytogenetics
  • genetic screening/counselling
  • molecular genetics

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  • Funding PD, KD, and HVE are Clinical Investigators of the Fund for Scientific Research, Flanders, Belgium. This work was supported by grant G019907N from the FWO-Vlaanderen to PD and in part by grants from the IWT (SBO-60848) and GOA/2006/12, and the SymBioSys Center of Excellence (Research Council, K.U.Leuven, EF/05/007) to JRV and KD. BD was partially supported by grant EO/06/32 of the K.U. Leuven, Belgium.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Hospital Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.