Open AccessRefinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1
Author(s) -
Aaron Theisen,
Jill A. Rosenfeld,
Kate Shane,
Kim L. McBride,
Joan Atkin,
Colette Gaba,
Joe J. Hoo,
Thaddeus W. Kurczynski,
Rhonda E. Schnur,
Lauren B. Coffey,
Elaine H. Zackai,
Lisa A. Schimmenti,
Neil Friedman,
M. Zabukovec,
Susie Ball,
Roberta A Pagon,
Ann Lucas,
Cam Brasington,
J. Edward Spence,
Susan Sparks,
Valerie Banks,
Wendy E. Smith,
Tami Friedberg,
Philip Wyatt,
Michelle R. Aust,
Raymond C. Tervo,
Amy Crowley,
David Skidmore,
Allen N. Lamb,
B. Ravnan,
Trilochan Sahoo,
Roger A. Schultz,
Beth S. Torchia,
Michael Sgro,
David Chitayat,
Lisa G. Shaffer
Publication year - 2010
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000328405
Subject(s) - microcephaly , syndactyly , ectrodactyly , genetics , brachydactyly , genetic heterogeneity , foot (prosody) , haploinsufficiency , medicine , biology , phenotype , pediatrics , ectodermal dysplasia , gene , short stature , linguistics , philosophy
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.