The appendicular skeleton is formed by the bones and joints. There all the soft tissues are organized around them to form the upper limb (1). The skeleton of the upper limb consists of two segments: the pectoral girdle, located proximally, made up by the clavicle and the scapula, which are responsible for joining the upper limb to the pectoral region, mainly through muscles, rather than through ligaments (2). And the distal portion of the upper limb, made up of the humerus, radius and ulna bones and the carpal and hand bones (3, 4, 5) (Figure 1 D)

Figure 1. Figure 1. Embryological development of the upper limb

(A) Embryo at the end of the fourth week of development, which illustrates the formation of the four buds, two of upper limbs and two lower limbs, respectively. An enlargement of the bud is shown on the right, which highlights the areas of the apical ectoderm crest in the distal axis, where the fibroblast growth factor (FGF) is found in greater concentration (orange triangle and margin) and the progress zone (underlying mesoderm, yellow triangle illustrate their greater concentration towards proximal) differentiating the proximal axis. (B) The anterior-posterior and dorsal-ventral axes are shown with the main molecules for their determination: Sonic hedgehog (SHH) on the fifth digit that defines the posterior axis; its absence determines the anterior axis. On the dorsal axis, WNT-7A, which establishes its location, and Engrailed-1 (EN-1), the ventral structures. (C) Illustration of the proximal and distal axis and the five digits located in the distal axis. (D) Presentation of the four portions of the upper and lower limbs from their embryonic origin; they correspond from proximal to distal to the stylopod (humerus and femur), zeugopod (forearm or leg structures), followed by the mesopod (carpus or tarsus, respectively) and autopod (metacarpus, metatarsus and phalanges).

Likewise, the upper limb is divided topographically into regions called the shoulder, the arm, the forearm, the carpus and the hand, where each of the upper limbs is made up of 32 bones (2,4,5). From proximal to distal, the arm is made up of the humerus, and distal to the arm, the forearm houses the ulna and radius. In the most distal region of the upper limb is the hand, which includes the wrist with eight carpal bones, the palm (five metacarpal bones) and the fourteen phalanges of the fingers (2).

The appendicular skeleton provides support and insertion to the muscles and tendons responsible for limb movement (1). The movements carried out by the upper limbs are very extensive, thanks to the synovial joints that join the different bones: flexion, generated mainly by muscles located in the anterior zone of the limb, extension, generated by the muscles of the posterior zone, pronosupination, which is specific and exclusive of the region of the forearm, and the most important: grip and clamp, made by the thumb in the region of the hand (3).

Finally, irrigation and innervation are sectorized from proximal to distal from the subclavian artery, coming from the aortic arch and the brachial plexus nerves, giving rise to the radial nerve, with motor information for the posterior area of the upper limb; the muscular-cutaneous nerve, in charge of the muscular action for the anterior face of the arm; the median nerve, for the innervation of most of the muscles of the anterior region of the forearm and the thenar region of the hand, and the ulnar nerve, mainly for the innervation of the hypothenar and palmar region of the hand (3, 4, 5).

Due to the nature of this paper, we only describe the development of the skeletal component of the upper limb. The embryogenesis of the upper limb begins towards the end of the fourth gestation week with the formation of a bud or sprout. These buds are formed by a series of reciprocal inductions between mesoderm and ectoderm, highly controlled by the expression of transcription factors and paracrine factors in time and space (6,7). Limb buds correspond to the proliferation of the mesenchyme, derived from the lateral plate of the mesoderm, which will originate some cartilaginous molds, which later ossify and give rise to the skeletal tissue at the height of the C5 cervical vertebrae and up to the T2 thoracic vertebrae. This proliferation is regulated by a close interaction with the superjacent ectoderm, called the apical ectodermal crest, which gives rise to the structures in three spatial axes: proximal/distal, dorsal/ventral, anterior/posterior. Once the skeletal component is formed, from the somitic mesoderm, flanking each side of the neural tube, will give rise to the soft tissues of the limb (8).

The upper limb bud grows temporarily, from proximal to distal, and generates cartilaginous molds in four different portions (Figure 1) consisting of the stylopod, which will give rise to the structures of the humerus and the arm in the upper limb; followed by the zeugopod, which comprises the structures that will give rise to the radius, the ulna, the associated structures of the forearm; the zeugopod zone is followed by the mesopod, which will give rise to the carpal structures, and the autopod zone, which will finally give rise to the hand or foot structures, and will be the most distal musculoskeletal structure (8,9).

Once the cartilaginous tissue blastemas are formed, the endochondral ossification will take place (Figure 2), which is typical of the appendicular skeleton (8).

Figure 2.

Note: Upper limb of a 15-week fetus, illustrated with cartilaginous molds that will differentiate into bone tissue to give rise to the formation of the palm bones through endochondral ossification, typical of the appendicular skeleton. The distal radio-ulnar and radio-carpal joints can be observed, as well as the joint between the first and second carpal row.

Congenital upper limb malformations are a common entity. It is estimated to occur in about 2.3 out of every 1000 live births (12). The prevalence of congenital upper limb malformations in the United States ranges between 0.16% and 0.18%. However, it is clear that it varies with a regional and ethnic correlation. Studies carried out in Finland, Canada and Australia report that the incidence of upper limb abnormalities ranges between 3.4 and 5.3 per 10,000 live births (13).

In Colombia, Zarante et al. (14) analyzed congenital malformations in 52,744 births in the cities of Manizales, Ubaté and Bogotá between 2001 and 2008. Their findings showed that upper limb malformations were the third most prevalent, among which polydactyly had an incidence of 21.2 per 10,000 live births. In general, this malformation was described more frequently in male patients (14). It should be noted that it is compatible with life, does not tend to get worse and improves significantly in terms of secondary disability with early medical intervention, which highlights the importance of recognizing it early.

However, the association between congenital upper limb malformations and potentially lethal syndromes should not be underestimated. Mortality among live-born patients with upper limb malformations has been documented to range between 14% and 16% in the first year of life; therefore, a comprehensive evaluation of these patients is required, as well as a complete examination of organs in the setting of a fetal necropsy (13). Other authors state that up to 18% of these patients have died by 6 years of age as a result of the syndromic association of the upper limb malformation (12). It is estimated that between 5% and 20% of patients with upper limb malformations have some syndrome that must be comprehensively evaluated by a multidisciplinary group of health professionals, in order to provide timely management (12).

Within the spectrum of congenital upper limb malformations, the most reported include failure of differentiation, followed by failure of duplication and formation abnormalities (12). In general, it has been identified that there is a higher prevalence of congenital upper limb malformations in men than in women, with a ratio of 3:2, respectively (12). Up to 50% of the patients have bilateral malformations, and in 17% of them multiple upper limb malformations are identified (12).

The photographic and histological documentation of congenital upper limb malformations used for this paper was taken from fetal necropsies performed by the authors in Bogotá, Colombia, from November 2012 to March 2019. All were carried out within the framework of Colombian legislation and had the informed consent of the parents or guardians. Photographic images and histological samples protect the identity of fetuses, relatives or guardians.

Based on the clinical cases, the following keywords were searched in the PubMed, SciELO and LILACS databases: upper limb congenital malformation, upper limb failure of formation, upper limb failure of differentiation, syndactyly, phocomelia, club hand, upper limb duplication, polydactyly, upper limb overgrowth, upper limb undergrowth, constriction ring syndrome, Swanson upper limb congenital malformation classification. To describe the diagnosis and differential diagnosis, only review articles and case reports with an emphasis on diagnostic criteria were included, in Spanish and English, without date restrictions.

The case corresponds to a fetus of approximately 10 weeks of gestation with malformation of both upper limbs (Figure 3). It was classified as a type I bilateral upper limb malformation with failure of longitudinal formation. The right upper limb presents formation of the arm (stylopod) with deficiency of longitudinal formation. The zeugopod (forearm) is not present. On the contrary, presence of distal structures of the upper limb can be observed in the autopod, including appendages that rule out transverse deficiency of formation of the upper limb. For the left upper limb there is evidence of the presence of arm, forearm and parts attached to the hand with longitudinal growth deficiency of the limb.

Figure 3. Figure 3. Fetus with type I bilateral upper limb malformation with failure of longitudinal formation

(A) The red arrow indicates the right upper limb with failure of longitudinal formation. Note the presence of distal structures of the upper limb, including appendages, which rules out transverse deficiency of formation of the upper limb. The white arrow points to the upper left limb with longitudinal growth deficiency. (B) Detail of the left upper limb showing the presence of hand appendages (black arrow) with longitudinal growth deficiency of the limb.

The case corresponds to a 9-week fetus with malformation due to longitudinal growth deficiency of the right upper limb (Figure 4A). There is a unilateral phocomelia with only one hand structure, so it is a case of true right phocomelia (Figure 4B). Phocomelia is a congenital anomalous condition, in which the proximal component of the upper limb (humerus, radius and ulna) is absent or markedly hypoplastic with the presence of a hand component. Phocomelia refers to the similarity of the upper limb to the fin of a seal (15). Additionally, the complete absence of the left upper limb is recorded, so it is classified as a true amelia of the upper left limb (Figure 4C).

Figure 4. Figure 4. True phocomelia

Necropsy of a nine-week fetus (A) Side view of fetus with malformation due to longitudinal growth deficiency of the right upper limb (red arrow). Clear example of a true unilateral phocomelia. (B) Detail of the right upper limb with presence of skin appendages given by an incipient nail bed (white dotted arrow). (C) Left side view showing true amelia.

The case corresponds to a 25 week gestation fetus with radial longitudinal deficiency in association with lobster claw hand. The fetus has upper left limb malformation with significant hypoplasia at the radial border, indicated by a red arrow (Figure 5A). The back (Figure 5B) and the palm of the upper left limb can be seen with only two digits (Figure 5C). On the radial end, a digit, which corresponds to the hypoplastic thumb (Figure 5D); additionally, another digit with ulnar deviation, which corresponds to a hand with lobster claw morphology. The hypoplasia of the radial edge of the upper left limb is shown in Figure 5E.

Figure 5. Figure 5. Radial club hand

25-week gestation fetus with radial longitudinal deficiency in association with lobster claw hand. (A) Hypoplasia at the radial border indicated with a red arrow. (B) Back of the hand with lobster claw morphology. (C) Palm with two digits. (D) Hypoplastic thumb on the radial end; additionally, another digit with ulnar deviation. (E) Hypoplasia of the radial edge of the upper left limb.

Clinodactyly in a 38-week fetus. This malformation consists of a deviation of a finger in the coronal plane. It generally occurs due to an abnormal delta morphology of the middle phalanx of the fifth finger, which causes a deviation of more than 10 degrees of the distal interphalangeal joint (Figure 6).

Figure 6. Figure 6. Clinodactyly

38-week fetus with Down syndrome. (A) A middle phalanx of the fifth finger with wedge morphology is observed (red arrow). (B) Representation of a coronal view of a normal phalanx. (C) Representation of a coronal view of a wedge-shaped phalanx.

The case corresponds to an anomaly in a 38-week fetus, characterized by the existence of extra digits in the hands. In the palmar view of the upper left limb of the fetus, a supernumerary pre-axial digit is observed (Figure 7A). Additionally, in the upper right limb there is thumb duplication associated with syndactyly of the supernumerary digit (Figure 7B). Therefore, this fetus has bilateral pre-axial polydactyly associated with right upper limb syndactyly between the supernumerary finger and the thumb.

Figure 7. Figure 7. Polydactyly

(A) Supernumerary pre-axial digit (white arrow) of the upper left limb in palmar view. (B) Thumb duplication associated with syndactyly of the supernumerary digit (white bracket) of the upper right limb of the same fetus.

The case corresponds to a 40-week fetus with disproportionately short fingers. There is a difference between the length of the palm indicated with the white bracket and the region of the digits, indicated with the red bracket (Figure 8).

Figure 8. Figure 8. Brachydactyly. 40-week fetus with brachydactyly

This case corresponds to a 35-week fetus that, due to amniotic bands, suffered constriction of the second digit of the right hand, for which it presented an ischemic process.

Figure 9. Figure 9. Acrosyndactyly

(A) Vestiges of the constriction bands (white dotted arrow). Distal to these is the ischemic digit. (B) Detail of the dorsal region of the second digit. Ischemic process (red arrow) in the affected digit, distal to the constriction bands.

Upper limb malformations can be caused by a transverse interruption or a longitudinal interruption in limb formation.

Failure of differentiation or separation of parts of the upper limb comprises the second group of congenital malformations described by Swanson. They include failures of soft tissues separation or even bone component separation (16). In this second group are all the malformations in which all the basic units of the upper member develop; however, not until its final form, so it does not reach the expected differentiation. Malformations can occur in any area of the upper limb. The most common included within this group are syndactyly, symphalangism or contracture due to failure of formation of muscles, ligaments or capsular structures.

These are the malformations that occur due to early alterations in embryonic development with changes in the apical ectoderm, zone of ectopic polarizing activity and SHH signaling. The spectrum of penetrance ranges from slight duplications, in the case of digits or skin appendages, to severe cases of duplication of the whole hand in patients with mirrored hands, or even duplication of the whole upper limb. Polydactyly, a malformation within this category, must be classified into pre-axial and post-axial duplications, according to its location with respect to the axis of the hand.

Upper limb malformations due to overgrowth can affect the entire limb. It is attributed to an overgrowth of the skeletal components of the limb with soft tissues of usual morphology. They include an increase in the size of the arm, forearm, hand or digits (12,16).

They refer to all forms of hypoplasia of the upper limb or parts of it, that is, it corresponds to the whole limb, only arm, forearm, hand or hypoplasia of one or more digits (12,16). They must be distinguished from the congenital malformations of the first group in Swanson classification, and for this it is necessary to consider that in cases of hypoplasia there are no missing skeletal or soft tissue parts, unlike cases of longitudinal growth deficiency. On the contrary, the parts of the limb are complete, although involuted, resulting in limb hypoplasia. The most distal expression of cases in this category includes nail hypoplasia. Although it can occur in proximal structures and affect only the arm, forearm, hand, metacarpus or phalanges in isolation or in combination with any of the mentioned structures (12,16, 58, 59).

Their frequency is estimated at 1 per 1,200 live births (65.66). These are congenital malformations resulting from a sequence of events leading to focal limb necrosis. This malformation occurs mainly during the post-embryonic stage. That is, it does not correspond to a failure in the embryonic development of the limb, but to an amputation by annular bands coming from chorionic tissue that are organized in the form of a tight band on the limb at any level, so that they produce ischemia, necrosis and intrauterine amputation of the most distal remnants, with scarring of the stump in that area (Figure 9). In the most severe cases, amputation of the entire limb occurs, but it can be at any level (12,16, 65, 67).

It is called acrosyndactyly or pseudosyndactyly in patients or fetuses in which a fusion of the digits is generated as part of the healing process to an injury due to amniotic band syndrome, in a patient or fetus in which there was no failure in the process of interdigital apoptosis and the digits were adequately formed (12, 65).

This is the last group of congenital upper limb malformations described by Swanson. It includes patients who have failure of formation of the upper limb as a result of alterations in generalized skeletal development; for example, in the case of patients with dyschondroplasia, achondroplasia, diastrophic dwarfism and congenital multiple arthrogryposis (12,16). The review of each of these pathologies and their manifestations exceeds the objective of this article.