Tuesday 31 August 2004
Split-hand/split-foot malformation (SHFM) 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.
Split hand or cleft hand results from a longitudinal deficiency of the central digits. Two types exist (typical and atypical), probably related to 2 different etiologies: typical cleft hand probably results from fusion of digits, atypical cleft is probably caused by necrosis secondary to a vascular insult.
typical cleft hand (1/90000 live births)
- deep and "V" shape central defect
- Syndactyly commonly affects the residual fingers. The anomaly is often bilateral and affects also frequently the feet.
- The transmission is X-linked dominant with incomplete penetrance.
- Typical cleft hand can be isolated, or associated with other anomalies (cleft lip or palate, absent ulna, etc.) or syndromes (Roberts syndrome, split hand-foot syndrome) (Fig 22).
atypical cleft hand
- The rarer atypical cleft hand (1/150000 live births) has a wider "U"-shaped deformation. The anomaly is often unilateral, and beside brachysyndactyly, is usually isolated.
- The Poland syndrome can be associated with this type of ectrodactyly.
Five loci for isolated SHFM (nonsyndromal SHFM) have been mapped.
SHFM1 at 7q21-7q22: DSS1 gene
SHFM2 (MIM.313350) at Xq26
SHFM3 (MIM.600095) at 10q24-q25
SHFM4 (MIM.605289) at 3q27: TP63 gene (MIM.603273)
SHFM5 (MIM.606708) on 2q31.
Associations (syndromal SHFM)
ectodermal dysplasia-ectrodactyly syndromes
- EEM syndrome (ectodermal dyslasia, ectrodactyly and macular dystrophy) (MIM.225280)
- EEC syndromes (ectrodactyly, ectodermal dysplasia and cleft lip/palate) (MIM.129830) (MIM.129900) (#7939823#)
- EEC1 at 7q11.2-q21.3 (MIM.129900)
- EEC2 at Chr.19 (MIM.602077)
- EEC3 at 3q27 (MIM.604292)
palate cleft-ectrodactyly association syndrome
bilateral tibial agenesis with ectrodactyly (MIM.119100) (tibial aplasia)
Roberts syndrome (#177235#)
Smith-Lemli-Opitz syndrome (#9475598#)
unilateral bifid femur with monodactylous ectrodactyly (MIM.228250)
brachydactyly-ectrodactyly with fibular aplasia or fibular hypoplasia (MIM.113310)
cleft palate, cardiac defect, genital anomalies and ectrodactyly (MIM.600460)
autosomal recessive acrorenal syndrome (tetraectrodactyly and oligomeganephronic renal hypoplasia)
association ectrodactyly-distal phocomelia (#12416640#, #8740915#)
association ectrodactyly-Wolf-Hirschhorn syndrome (#9482640#)
association bifid femur-monodactylous ectrodactyly (#7468656#)
association ectrodactyly-tibial hemimelia or tibial aplasia-ectrodactyly syndrome (Gollop-Wolfgang complex) (#10340652#, #8723107#)
association ectrodactyly-proximal femoral focal deficiency (#9217221#)
association ectrodactyly-ectodermal dysplasia and ventricular septal defect (#7939823#)
association monodactylous ectrodactyly-bifid femur (#7468656#)
pentalogy of Cantrell (#17154221#)
6q16 deletion (#8766142#)
6q21 deletion (#7726229#)
7q22 deletion (SHFM1 locus at 7q21) (#1741973#)
trisomy 18 (#8172239#)
oligodactyly (reduced number of well formed fingers)
Duijf PH, van Bokhoven H, Brunner HG. Pathogenesis of split-hand/split-foot malformation. Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R51-60. PMID: #12668597#
Chen CP, Hsu CY, Tzen CY, Chern SR, Wang W. Prenatal diagnosis of pentalogy of Cantrell associated with hypoplasia of the right upper limb and ectrodactyly. Prenat Diagn. 2007 Jan;27(1):86-7. PMID: #17154221#