Refinement of the region for split hand/foot malformation 5 on 2q31.1

A. Theisen, J. A. Rosenfeld, K. Shane, K. L. McBride, J. F. Atkin, C. Gaba, J. Hoo, T. W. Kurczynski, R. E. Schnur, L. B. Coffey, E. H. Zackai, L. Schimmenti, N. Friedman, M. Zabukovec, S. Ball, R. Pagon, A. Lucas, C. K. Brasington, J. E. Spence, S. SparksV. Banks, W. Smith, T. Friedberg, P. R. Wyatt, M. Aust, R. Tervo, A. Crowley, D. Skidmore, A. N. Lamb, B. Ravnan, T. Sahoo, R. Schultz, B. S. Torchia, M. Sgro, D. Chitayat, L. G. Shaffer

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: Deletions that encompass 2q31.1 have been proposed as a microdeletion syndrome with common clinical features, including intellectual disability/developmental delay, microcephaly, cleft palate, growth delay, and hand/foot anomalies. In addition, several genes within this region have been proposed as candidates for split hand-foot malformation 5 (SHFM5). Methods: To delineate the genotype-phenotype correlation between deletions of this region, we identified 14 individuals with deletions at 2q31.1 detected by microarray analysis for physical and developmental disabilities. Results: All subjects for whom detailed clinical records were available had neurological deficits of varying degree. Seven subjects with deletions encompassing the HOXD cluster had hand/foot anomalies of varying severity, including syndactyly, brachydactyly, and ectrodactyly. Of 7 subjects with deletions proximal to the HOXD cluster, 5 of which encompassed DLX1/DLX2, none had clinically significant hand/foot anomalies. In contrast to previous reports, the individuals in our study did not display a characteristic gestalt of dysmorphic facial features. Conclusion: The absence of hand/foot anomalies in any of the individuals with deletions of DLX1/DLX2 but not the HOXD cluster supports the hypothesis that haploinsufficiency of the HOXD cluster, rather than DLX1/DLX2, accounts for the skeletal abnormalities in subjects with 2q31.1 microdeletions.

Original languageEnglish (US)
Pages (from-to)262-271
Number of pages10
JournalMolecular Syndromology
Issue number5
StatePublished - May 2011


  • 2q31.1
  • DLX1/DLX2
  • HOXD
  • Limb anomalies
  • Microdeletion
  • SHFM5


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