Alternative titles; symbols
ORPHA: 2440; DO: 0090027;
Cytogenetic location: Xq26 Genomic coordinates (GRCh38): X:129,500,001-138,900,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xq26 | Split hand/foot malformation 2 | 313350 | X-linked | 2 |
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals (Elliott and Evans, 2006).
For additional phenotypic information and a discussion of genetic heterogeneity of split-hand/split-foot malformation, see SHFM1 (183600).
Ahmad et al. (1987) described a Pakistani kindred in which 36 members in 7 generations had split-hand and split-foot anomaly. The full expression of the trait, monodactylous or split hand and split foot, mainly of the lobster-claw type, was present in 33 males and 3 females. Other females showed a distinctly milder expression of the trait, usually in the form of partial syndactyly, metacarpal and phalangeal hypoplasia, and malformation of the bones of the hand. The distribution of affected members in the pedigree was considered to be compatible with X-linked inheritance. Hemizygous males and presumably homozygous females exhibit the typical split-hand/split-foot anomaly, whereas only part of the obligatory heterozygous females show the milder expression. The pedigree contained one example of father and son affected, but it seemed in this case that the mother was heterozygous because there was mild expression of the trait and 2 daughters were apparent homozygotes. The authors referred to the article by Bujdoso and Lenz (1980) proposing 3 distinct types.
Faiyaz ul Haque et al. (1992) performed linkage studies in the Pakistani kindred reported by Ahmad et al. (1987). No recombination was found between the disease locus and the loci DXS294 and HPRT (308000); maximum lod = 5.13 and 4.43, respectively. Thus, linkage analysis suggested that the gene for X-linked split hand/split foot anomaly is located at Xq26.
Faiyaz-Ul-Haque et al. (2005) performed additional linkage studies in the Pakistani kindred reported by Ahmad et al. (1987) and narrowed the SHFM2 locus to a 5.1-Mb region on Xq26.3 between markers DXS1114 and DXS1192.
Exclusion Studies
In the Pakistani kindred with SHFM2, Faiyaz-Ul-Haque et al. (2005) screened the exons and exon/intron boundaries of 19 candidate genes in the Xq26.3 region and did not identify any mutations.
Palmer et al. (1994) suggested that since split-hand/split-foot is a malformation, not a deformity, the gene symbol should be SHSF. The HUGO nomenclature committee determined in 1994 that split hand/foot malformation should be symbolized SHFM.
Ahmad, M., Abbas, H., Haque, S., Flatz, G. X-chromosomally inherited split-hand/split-foot anomaly in a Pakistani kindred. Hum. Genet. 75: 169-173, 1987. [PubMed: 3817811] [Full Text: https://doi.org/10.1007/BF00591081]
Bujdoso, G., Lenz, W. Monodactylous splithand-splitfoot: a malformation occurring in three distinct genetic types. Europ. J. Pediat. 133: 207-215, 1980. [PubMed: 7389732] [Full Text: https://doi.org/10.1007/BF00496078]
Elliott, A. M., Evans, J. A. Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. Am. J. Med. Genet. 140A: 1419-1427, 2006. [PubMed: 16688749] [Full Text: https://doi.org/10.1002/ajmg.a.31244]
Faiyaz ul Haque, M., Uhlhaas, S., Knapp, M., Schuler, H., Friedl, W., Ahmad, M., Propping, P. X-chromosomal split-hand/split-foot anomaly maps to Xq26. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A189 only, 1992.
Faiyaz-Ul-Haque, M., Zaidi, S. H. E., King, L. M., Haque, S., Patel, M., Ahmad, M., Siddique, T., Ahmad, W., Tsui, L.-C., Cohn, D. H. Fine mapping of the X-linked split-hand/split-foot malformation (SHFM2) locus to a 5.1-Mb region on Xq26.3 and analysis of candidate genes. Clin. Genet. 67: 93-97, 2005. [PubMed: 15617554] [Full Text: https://doi.org/10.1111/j.1399-0004.2004.00369.x]
Palmer, S. E., Scherer, S. W., Kukolich, M., Wijsman, E. M., Tsui, L.-C., Stephens, K., Evans, J. P. Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation. Am. J. Hum. Genet. 55: 21-26, 1994. [PubMed: 7912888]