SHFM is a heterogeneous condition caused by abnormalities at one of multiple loci, including SHFM1 (SHFM1 at 7q21-q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX 2 at 2q31).

Detailed studies of a number of mouse models for ectrodactyly have also revealed that a failure to maintain median apical ectodermal ridge (AER) signalling can be the main pathogenic mechanism in triggering this abnormality.

[9] A number of factors make the identification of the genetic defects underlying human ectrodactyly a complicated process: the limited number of families linked to each split hand/foot malformation (SHFM) locus, the large number of morphogens involved in limb development, the complex interactions between these morphogens, the involvement of modifier genes, and the presumed involvement of multiple gene or long-range regulatory elements in some cases of ectrodactyly.

[9] Syndromes in which ectrodactyly is associated with other abnormalities can occur when two or more genes are affected by a chromosomal rearrangement.

[13] The p63 gene plays a critical role in the development of the apical ectodermal ridge (AER), this was found in mutant mice with dactylaplasia.

In vivo tests showed that limb anomalies were found alone or in combination with cleft hand when they were given Myleran.

[citation needed] The social and stigmatising aspects of a cleft hand require more attention.

Indications for early treatment are progressive deformities, such as syndactyly between index and thumb or transverse bones between the digital rays.

Techniques described by Ueba, Miura and Komada and the procedure of Snow-Littler are guidelines; since clinical and anatomical presentation within the types differ, the actual treatment is based on the individual abnormality.

[citation needed] Table 4: Treatment based on the classification of Manske and Halikis The goal of this procedure is to create a wide first web space and to minimise the cleft in the hand.

[6] Transverse flaps are used to resurface the palm, the dorsal side of the transposed digit and the ulnar part of the first web space.

In City of God (426 A.D.), St. Augustine remarks: At Hippo-Diarrhytus there is a man whose hands are crescent-shaped, and have only two fingers each, and his feet similarly formed.

The classification in which typical and atypical cleft hand are described was mostly used for clinical aspects and is shown in table 1.

[citation needed] Ectrodactyly is not only a genetic characteristic in humans, but can also occur in frogs and toads,[24] mice,[25] salamanders,[26] cows,[9] chickens,[9] rabbits,[9] marmosets,[9] cats and dogs,[27] and even West Indian manatees.

[9] The following examples are studies showing the natural occurrence of ectrodactyly in animals, without the disease being reproduced and tested in a laboratory.

[24] After roughly 22,733 individuals were examined during field studies, it was found that only 49 wood frogs had the ectrodactyly deformity.

[24] In a study performed by the Department of Forestry and Natural Resources at Purdue University, approximately 2000 salamanders (687 adults and 1259 larvae) were captured from a large wetland complex and evaluated for malformations.

Ferreira, a case of ectrodactyly was found in a two-month-old male mixed Terrier dog.