Ectrodactyly, sometimes referred to as the “lobster-claw syndrome”[1] involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM).[2] The hands and feet of people with ectrodactyly are often described as "claw-like" and may include only the thumb and one finger (usually either the little finger, ring finger, or a syndactyly of the two) with similar abnormalities of the feet.[3]
| Ectrodactyly | |
|---|---|
| Classification and external resources | |
| ICD-10 | Q71.6 |
| ICD-9 | 755.4 |
| OMIM | 225300 |
| DiseasesDB | 32141 |
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A large number of human gene defects can cause ectrodactyly. The most common mode of inheritance is autosomal dominant with reduced penetrance, while autosomal recessive and X-linked forms occur more rarely.[4] Ectrodactyly can also be caused by deletions, translocations, and inversions in chromosome 7 (7q).[5] The deletions in 7q can result in a contiguous gene syndrome that includes growth impairment, microcephaly, craniofacial manifestations, hernias, hearing loss, and mental retardation.[5] Translocations in 7q do not have as many abnormalities but are generally associated with most hearing loss cases.[5] This is why most cases of ectrodactyly are generally accompanied by another abnormality or linked to another syndrome (ex. EEC, LMS, ECP).[6] 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.[4] 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.[4] In the clinical setting these genetic characteristics can become problematic and making predictions of carrier status and severity of the disease impossible to predict.[7]
In 2011, a novel mutation in DLX5 was found to be involved in SHFM.[8]
As mentioned in the Genetics section, ectrodactyly can be caused by various changes to 7q. When 7q is altered by a deletion or a translocation ectrodactyly can sometimes be associated with hearing loss.[5] Ectrodactyly, or Split hand/split foot malformation (SHFM) type 1 is the only form of split hand/ malformation associated with sensorineural hearing loss.[5]
The functional utility of the malformed limbs is discussed in issue 2481 of The British Medical Journal.[9] The affected persons can perform work that requires skillful manipulation, regardless of their handicap. The article says, “The needlework of some of the females is good; the handwriting of most is excellent. One individual is a boot maker, two others drive cabs, none finding difficulty in clothing themselves, and most do so with extraordinary rapidity, even to the lacing of boots....It is said of one that he is able in this way to lift pins from the floor with his feet.” Those with ectrodactyly are contributing members of society with their own jobs and careers;[1] many choose to have families and raise children.[1] In most daily tasks the health condition appears to have a small effect on their functionality. In 2006, the London Tate exhibition Single Shot featured a video of an unidentified person with ectrodactyly skillfully playing the piano with only four fingers.[10]
Ectrodactyly is not only a genetic characteristic in humans, but can also occur in frogs and toads,[11] mice,[12] salamanders,[13] cows,[4] chickens,[4] rabbits,[4] marmosets,[4] cats and dogs,[14] and even West Indian manatees.[4] The following examples are studies showing the natural occurrence of ectrodactyly in animals, without the disease being reproduced and tested in a laboratory. In all three examples we see how rare the actual occurrence of ectrodactyly is.
The Department of Biological Sciences at the University of Alberta in Edmonton, Alberta performed a study to estimate deformity levels in Wood Frogs in areas of relatively low disturbance.[11] After roughly 22,733 individuals were examined during field studies, it was found that only 49 Wood Frogs had the ectrodactyly deformity.[11]
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.[13] Among the 687 adults, 54 (7.9%) were malformed. Of these 54 adults, 46 (85%) had missing (ectrodactyly), extra (polyphalangy) or dwarfed digits (brachydactyly).[13] Among the 1259 larvae, 102 were malformed, with 94 (92%) of the malformations involving ectrodactyly, polyphalangy, and brachydactyly.[13] Results showed few differences in the frequency of malformations among life-history changes, suggesting that malformed larvae do not suffer substantially higher mortality than their adult conspecifics.[13]
In a “Journal of Heredity” published by the Oxford Journals a study was performed to test allele frequencies in domestic cats. Among the 265 cats observed, there were 101 males and 164 females. Only one cat was recorded to have the ectrodactyly abnormality,[15] illustrating this rare and unique disease. According to M.P. Ferreira, a case of ectrodactyly was found in a two month old male mixed Terrier dog.[16] In another study, Carrig and co-workers also reported a series of 14 dogs[17] with this abnormality proving that although ectrodactyly is an uncommon occurrence for dogs, it is not entirely unheard of.
Ectrodactyly is frequently seen with other congenital anomalies, or other birth defects.[4] Syndromes in which ectrodactyly is associated with other abnormalities can occur when two or more genes are affected by a chromosomal rearrangement.[4] Disorders associated with ectrodactyly include Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) syndrome, which is closely correlated to the ADULT syndrome and Limb-mammary (LMS) syndrome, Ectrodactyly-Cleft Palate (ECP) syndrome, Ectrodactyly-Ectodermal Dysplasia-Macular Dystrophy syndrome, Ectrodactyly-Fibular Aplasia/Hypoplasia (EFA) syndrome, and Ectrodactyly-Polydactyly. More than 50 syndromes and associations involving ectrodactyly are distinguished in the London Dysmorphology Database.[6]
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