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)
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