There was an Ape in the days that were earlier;Centuries passed, and his hair became curlier;Centuries more gave a thumb to his wrist—Then he was MAN, and a Positivist.(Edward James Mortimer Collins [1827-1876], from: "The British Birds. A Communication from the Ghost of Aristophanes"1)
There was an Ape in the days that were earlier;
Centuries passed, and his hair became curlier;
Centuries more gave a thumb to his wrist—
Then he was MAN, and a Positivist.
(Edward James Mortimer Collins [1827-1876], from: "The British Birds. A Communication from the Ghost of Aristophanes"1)
The human hand evolved from a specialized fin some 400 million years ago, and its many shapes and purposes have culminated in a masterful instrument capable of great skill—and a source of great despair. When things go awry in development, aberrancies range from the appearance of simple webbing and skin tags to the disappearance of the radius and mirror hand duplication. As surprising and rare as these conditions are, they occur in patterns of morphologic consistencies, although the inciting genetic programming and signaling pathways are complex, interrelated, and only provisionally understood. Identifying the gene's role in evolution has hallmarked much of evolutionary study in the twentieth century, with the discovery of genetic aberrations associated with anomalies often providing a clue to the normal orchestration and development of the limb bud.
The scrutiny of limb-development morphology hearkens back to the nineteenth century natural scientists, who observed phenotypic features of human limbs compared with those of other primates and mammals. In his essay, commonly known as the Bridgewater Treatise2, Sir Charles Bell commented on the unique "perfection" of the human hand in its full array of possibilities as compared with the analogous structure in the chimpanzee, the horse, and the bird, among other animals. Although Charles Darwin first espoused natural selection as the mechanism of evolution in the Origin of Species in 1859 as a culmination of current thought and decades of observing insects and small exotic animals3, it was not until The Descent of Man in 18714 that he published his daring observations on the origin of Homo sapiens. His own children and the primates at the London Zoo provided much of the fodder; he was particularly intrigued with an orangutan—Quadrumana, as it was commonly known then—named Jenny, for her human gestures and behavior5. And Ernst Haeckel's controversial concept that ontogeny recapitulates phylogeny, meaning that the evolutionary history of the species is seen early in development but fades toward adulthood, introduced the concept that our ancestors had amphibious gills and tails, just like the embryonic human6.
Although argued and in part disproven by creationists and scientists alike, Haeckel's observations contribute to a continuum of modern evolutionary theory that begs one more hypothesis: that every congenital hand anomaly has an evolutionary cognate. The morphologic similarities of congenital anomalies compared with those of extant primates and evolutionary forbears appear consistently, as if the recipe remains encoded within us until some quirk of nature chooses to let it surface. Like any theory, this hypothesis can never be proven, but supporting evidence stacks in favor. The evidence follows.
The educated Charles Darwin (1809-1882)—student of medicine and the Church of England, and married to a Wedgwood—was fascinated with the origin of words and the life of a language5. His similar observations of zoological ontogeny compared the dog embryo and that of a human (Fig. 1), noting the many homologous structures between them4. His "tree of life," a deductionist map of evolutionary change, holds up well to modern-day evolutionary trees that include the primitive amphibian Eusthenopteron from 380 million years ago and hominin Lucy Australopithecus afarensis from approximately 4 million years ago (Fig. 2 of this paper3, and see cladogram in Fig. 1 of M.W. Marzke's "Upper-Limb Evolution and Development," in this supplement).
Darwin's contemporary, William Henry Flower, a British surgeon and comparative anatomist, published the seminal An Introduction to the Osteology of the Mammalia on vertebrate morphology, forming the basis for twentieth-century taxonomy7. In Functional Morphology of the Evolving Hand and Foot8, modern-day anthropologist O.J. Lewis has refined the evolutionary templates that provide the basis for the proposed hypothesis. The use of the word template intentionally borrows from the physical pattern used in woodworking or architecture to reproduce a design, as well as the biochemical term for a building block as a model for larger molecules.
Conditions such as ulnar impaction and the problematic vascularity of the distal pole of the scaphoid may be subtle versions of phylogenetic templates. In addition, several hand and wrist cognates such as polydactyly and Madelung deformity can be explained with this template approach. These are discussed below.
As terrestrial apes developed trunk musculature and a pelvis that afforded upright posture and bipedalism, the brain and hand coevolved, and the upper-limb sphere of motion increased. Although ulnar impaction assists animals with upper-limb axial load bearing, it does not permit rotational activity and thus limits upper-limb motion. Accordingly, the ulna receded to accommodate forearm rotation. Marzke postulates that the hamate facet found in type-II cadaveric lunates, which is associated with size-dependent facet arthritis and altered radioulnar kinematics9,10, suggests a remnant of stabilization for knuckle-walking (personal communication, February 2008). Radial and ulnar prehension created the cupping needed for tool use, with the thumb making the greatest strides in development. Thumb development was not without its price, however; the necessary laxity of the saddled trapeziometacarpal joint, its mismatch of smaller metacarpal size relative to trapezial size, and the necessity of play affording circumduction with paradoxic needs for stable positioning has predisposed this joint to wear out. (Whether the female predilection for arthritis of this joint accompanies an evolutionarily advanced status remains to be seen.)
A few generalities should be borne in mind when applying the concept of cognates to congenital anomalies. Evolution tends to favor simplicity, eliminating or fusing unwanted parts. According to Lewis and previous authors8, early amphibians had six or seven digits of the upper limb, providing a template for polydactyly (Fig. 3). The pentadactyl hand became the preferred configuration 180 million years ago.
In birds the manus—the anthropologic term given to the wrist, palm, and digits—becomes an aerodynamic foil, having undergone both fusion and loss11. In the bird embryo, however, phalanges are present, an example of ontogeny recapitulating phylogeny.
The ulna sometimes fuses to the humerus and bears less weight, or is even vestigial, as in bats and frogs. However, in most mammals that require forward propulsion, the ulna bears substantial load. The block-like wrist configuration of a primitive mammal shows the functional template of terrestrial animals today (Fig. 4). The elephant is one extant creature whose upper and lower limbs act as walking pillars, with both the fibula and radius as perfunctory contributions. Flower compared the manus of the tapir, rhinoceros, and horse, correlating the reduction of bones to function, with "complete suppression of the pollex"7 (Fig. 5). Extremes in wrist configuration exist between the saltatory (jumping) and cursor (running) animals that require forward propulsion, and the climbers that require side-to-side motion in addition to forward propulsion12. The runners and jumpers, in general, have deeply grooved block-like joints, whereas the climbers possess joints that accommodate rotation.
In most nonhuman primates, the ulna articulates with the pisiform and triquetrum, with a true meniscus acting as a gasket between the articulations (Fig. 6). As the trunk afforded upright posture, the ulna receded along with the true meniscus, allowing forearm rotation at the distal and proximal radioulnar joints. Combined with the rotation afforded by the glenohumeral joint, this provides a sphere of motion unique to humans.
The mammalian wrist has also evolved to eliminate or fuse certain carpal bones. The distal row of carpal bones 4 and 5 in Figure 4 evolved into the hamate, and the os centralia, present in early human development, fuses with the distal pole of the scaphoid by three months of gestation in humans and the knuckle-walking chimpanzee13,14. This fusion explains the retrograde and thus problematic vascularity of the scaphoid's distal pole.
Disproportionate shortening or lengthening of bones may occur, such as has occurred with the length of phalanges in hominins; the thumb in its recessed position is an obvious example. The variability of finger and thumb length in primates is postulated to occur from conflicting requirements for prehension and running, and the size of hand muscles varies accordingly. Fossil records suggest that the radius is getting longer and the hand is getting shorter, and although the third metacarpal is lengthening, the overall length of the third digit is shortening15.
The panda exhibits another example of lengthening: the panda's "thumb" is not a true thumb but a sixth "nubbin." Like its cousin the bear, the panda's first ray is in the plane of the other digits, essential for running and clawing. But unlike its omnivorous cousin, the panda is content to eat bamboo shoots all day long (Fig. 7). The "thumb" is an elongated carpal sesamoid with the adductor and abductor intrinsic attachments acting independently from the first ray, serving as a post for bamboo shoots16.
Presumably, in a world that revolves around humans, the fading away of unnecessary traits over millennia gives way to a more advanced being—or perhaps just a more adaptive one.
Specific hand and wrist cognates are discussed below.
As described above, early amphibians demonstrate extra digits (see Fig. 3). Human polydactyly varies and can manifest as simple nubbins or a complex variety of nubbins in both preaxial and postaxial manifestations. The dwarfism and postaxial polydactyly associated with Ellis-van Creveld syndrome, an autosomal recessive disorder linked to chromosome 4p16 and first identified in the Amish population, has provided an opportunity for more in-depth investigation of the link between morphology and genetic signaling17. This represents the isolation of a single mutation in a consanguineous population, and establishes the link between an evolutionary cognate and a genetic reason for unmasking a dormant trait. Genetic markers, in this analogy, presumably signal events that recall the tetrapod template of wrist and hand.
Whereas lower primates have a true meniscus at the radiocarpal joint, humans do not, as the ulna has receded. Instead of a v-shaped wrist with deep notching of the carpus as in monkeys, the load distribution across the radius, the triangular fibrocartilage complex, and the distal part of the ulna of the human wrist accommodates more of an arch, in accordance with the laxity required by the climbing vertebrate for lateral as well as forward movement13. The human embryo and early fetus, however, demonstrate this atavism, with a prominent styloid articulating with the pisiform and triquetrum (Figs. 8 and 9)18. In Madelung deformity, a hallmark of Léri-Weill dyschondrosteosis, a similar deformity occurs, and symptoms range from mild ulnar impaction to pronounced deformity and pain with rotation. Léri-Weill dyschondrosteosis is associated with known mutations in the SHOX gene, and recently has been reproduced in a chick model19.
Webbed fingers relate to the primordial fish fin, and the hand paddle differentiates into digits through the process of apoptosis as the embryo becomes a fetus. Incomplete differentiation causes simple syndactyly with only skin involvement, or bone involvement in the complex forms, with a variety of signaling abnormalities having been identified, including mutations in the fibroblast growth factor receptor 2 (FGFR2) gene in Apert syndrome20.
Distinct bones also develop through apoptosis, and growth plates are a manifestation of incomplete apoptosis. Secondary sites of ossification often represent previous phylogenetic or atavistic anatomy. The olecranon is such an example; its predecessor was a sesamoid like the patella8. If simplification is an evolutionary asymptote—the line approaching the curve toward zero yet never attained—then carpal coalition is an advanced trait. The avian limb and the leg of a horse, however, also demonstrate significant reduction in parts, so cautionary application of these rules is advised.
The great apes—other than human—all exhibit various forms of thumb hypoplasia; the relative long fingers to short stiff thumb provide the chimpanzee with a thumb more useful as a post than for prehension, effectively a Blauth type-2 reduction (Fig. 10)21.
The tetrapod template of the hand and forearm (Fig. 3) has more symmetry than the current template of radial and ulnar orientation as governed by the zone of polarizing activity, which was first described in chick embryos22. Ulnar dimelia (mirror hand) and central deficiency resemble these early tetrapod patterns; one need only see a koala to know this trait still remains in living homologues (Fig. 11). Camptodactyly might be explained by retained vestiges of contrahentes digitorum muscles; lost in human embryonic development with the exception of the adductor pollicis, they are ulnar-innervated intrinsic muscles thought to provide better grasp and branch negotiation for most monkeys, but absent in great apes23-25. Their frequency and attachments in primates vary, but they include connections between the metacarpal and proximal phalanges25, suggesting the typical pattern of the human palmar aponeurosis. The few reports of contrahentes muscles found in humans suggest more robust thenar and hypothenar musculature26, but the similarities between the primate and anomalous lumbrical muscles in camptodactyly or other aponeurotic bands are striking.
The surgeon has the opportunity to alter misdirected templates of congenital anomalies, sometimes "advancing" evolution with the stroke of the scalpel as with pollicization of an index finger in the case of an absent or severely hypoplastic thumb. Other times, however, surgical intervention may worsen the functional adaptation inherent in the anomaly. For example, closure of the cleft in a centrally deficient hand and wrist centralization for radial aplasia may provide little benefit or may even diminish function. The majority of surgical procedures described for deficiencies and duplications, including reduction and construction of duplicated digits, syndactyly release, tendon transfers and repositioning of the hypoplastic thumb, and ulnar leveling procedures for Madelung deformity, improve both the function and appearance of the hand.
The surgeon's desire to classify and create a language to better understand why things go wrong, for now at least, fits with the working hypothesis that hand and wrist anomalies exist as evolutionary cognates. Our current basis for understanding the genetic programming of congenital differences relies largely on the experimental study of homologous structures in animals quite dissimilar to our own morphology, and thus the genetic etiology and its complexity of expression remain obscure in most human conditions. Whether the cognate hypothesis will hold up when and if the genes for congenital limb differences have been thoroughly mapped and sequenced remains to be seen—but observation and preliminary evidence suggest a robust possibility. 
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