Two main types of cleft hands have been described. The ulnar cleft hand deformity is very rare and is characterized by two constant features: a deep cleft radial to the little finger and hypoplasia of the ulnar digits. The pathogenesis of ulnar clefts is unknown. The second type is the central cleft hand deformity, which is characterized by a soft tissue/bone defect in the hand centrally. Patients with central clefts also have several concurrent deformities in the remaining digits. This paper reviews the clinical features of three cases with ulnar cleft hands and 44 cases of central cleft hands, with special emphasis on concurrent deformities. The author’s hypothesis of pathogenesis for both types of clefts and their concurrent deformities is then offered.
Al-QattanMM. WNT pathways and upper limb anomalies. J Hand Surg Eur. 2011, 36: 9–22.
2.
Al-QattanMMYangYKozinSH. Embryology of the upper limb. J Hand Surg Am. 2009, 34: 1340–50.
3.
Al-QattanMMAl-MazyedMShamseldinHAl-KurayaFS. Dorsal dimelia: Report of two cases with an emphasis on the variation of phenotype expression and a search for candidate genes. J Hand Surg Eur. 2010, 35: 715–20.
4.
BaluthWFallinerA. Morphology and classification of cleft hands. Hand Chir Mikrochir Plast Chir. 1986, 18: 161–5.
5.
BarskyAJ. Cleft hand classification, incidence, and treatment. J Bone Joint Surg Am. 1964, 46: 1707–20.
6.
BouletAMMoonAMArenkielBRCapecchiMR. The roles of FgF4 and FgF8 in limb bud initiation and outgrowth. Dev Biol. 2004, 273: 361–72.
7.
ElliottAMEvansJA. Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. Am J Med Genet A. 2006, 140: 1419–27.
8.
ElliottAMReedMHEvansJA. Central ray deficiency with extensive syndactyly: A dilemma for classification. Genet Conus. 2009, 20: 27–43.
9.
FallinerAA. Analysis of anatomic variants in cleft hands. J Hand Surg Am. 2004, 29: 994–1001.
10.
Fernandez-TeranMRosMA. The apical ectodermal ridge: morphological aspects and signaling pathways. Int J Dev Biol. 2008, 52: 857–71.
11.
Hernandez-MartinezRCastro-ObreganSCovarrubiasL. Progressive inter-digital cell death: regulation by the antagonistic interaction between fibroblast growth factor 8 and retinoic acid. Development. 2009, 136: 3669–78.
12.
HoriiEMiuraTNakamuraR. Ulnar ray deficiency. A report of a family. J Hand Surg Br. 1994, 19: 244–7.
13.
KatoHIshiiSOginoTShionoH. Anomalous hands with cleft formation between the fourth and fifth digits. J Hand Surg. 1983, 8: 909–13.
14.
KrakowerMAMotoyamaJTsuiLC. Defecting the maintenance of the apical ectodermal ridge in the dactylplasia mouse. Develop Biol. 1998, 201: 78–9.
15.
LauferENelsonCEJohnsonRLSonic hedgehog and FGF4 act through a signaling cascade and feedback to integrate growth and patterning of the development limb bud. Cell. 1994, 79: 993–1003.
16.
Le LaconoNManteroSChiarelliARegulation of DLX5 and DLX6 gene expression by P63 is involved in EEC and SHFM congenital limb defects. Development. 2008, 135: 1377–88.
17.
LetticeLAHoriskoshiTHeaneySJDisruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc Natl Acad Sci USA. 2002, 99: 7548–53.
18.
LiuYLiuCYamadaYGrowth arrest specific gene 1 acts as a region-specific mediator of the FGF10/FGF8 regulatory loop in the limb. Development. 2002, 129: 5289–300.
19.
LuPMinowadaGMartinGR. Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function. Development. 2006, 133: 33–42.
20.
MaiselsDO. Lobster-claw deformities of the hands and feet. Br J Plast Surg. 1970, 23: 269–82.
21.
ManskePRHalikisMN. Surgical classification of central deficiency according to the thumb web. J Hand Surg Am. 1995, 20: 687–97.
22.
MarianiFVAhnCPMartinGR. Genetic evidence that FGFs have instructive role in limb proximal-distal patterning. Nature. 2008, 453: 401–5.
23.
MiuraT. Cleft hand involving only the ring and small fingers. J Hand Surg Am. 1988, 13: 530–5.
24.
MiuraTNakamuraRSuzukiMWatanabeK. Cleft hand, syndactyly and hypoplastic thumb. J Hand Surg Br. 1992, 17: 365–76.
25.
NaruseTTakaharaMTakagiMObergKCOginoT. Busulfan-induced central polydactyly, syndactyly, and cleft hand or foot: A common mechanism of disruption leads to divergent phenotypes. Dev Growth Differ. 2007, 49: 533–41.
26.
NiswanderLJeffreySMartinGRA positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature. 1994, 37: 609–12.
27.
OginoT. Cleft hand. Hand Clin. 1990a, 6: 661–71.
28.
OginoT. Teratogenic relation between central polydactyly, osseous syndactyly and cleft hand. J Hand Surg Br. 1990b, 15: 201–9.
29.
OginoT. Clinical features and teratogenic mechanisms of congenital absence of digits. Develop Growth Differ. 2007, 49: 423–531.
30.
PanmanLGalliALagardeNDifferential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and Gremlin 1 / FGF-mediated epithelial–mesenchymal signaling. Development. 2006, 133: 3419–28.
31.
SatakeHOginoTTakaharaMOccurrence of central polydactyly, syndactyly, and cleft hand in a single family: Report of five hands in three cases. J Hand Surg Am. 2009, 34: 1700–3.
32.
ShamseldinHEFadenMAAlAshramWAlKurayaFS. Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation. J Med Genet. 2012, 49: 16–20.
33.
ShimomuraYWajidMShapiroLChristianoAM. P-cadherin is a p63 target gene with a crucial role in the developing human limb and bud and hair follicle. Development. 2008, 135: 743–53.
34.
SunXMarianiFVMartinGR. Functions of FGF signaling from the apical ectodermal ridge in limb development. Nature. 2002, 418: 501–8.
35.
SuzukiDTHassoSMFallonJF. Unique SMAD 1/5/8 activity of the phalanx-forming region determines digit identity. PNAS. 2008, 105: 4185–90.
36.
TickleC. Making digit pattern in the vertebrate limb. Nat Rev. 2006, 7: 45–53.
WitteFDokasJNeuendorfFMundlosSStrickerS. Comprehensive expression analysis of all Wnt genes and their major secreted antagonist during mouse limb development and cartilage differentiation. Gene Expr Patterns. 2009, 9: 215–23.
39.
YuKOrnitzDM. FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximo distal axis. Development. 2008, 135: 483–91.
