Embryonic and fetal development of the human knee with an emphasis on the posterior cruciate ligament: a literature review

Introduction

The embryogenesis of the human knee has been described in many studies, with a focus on the cruciate ligaments due to their clinical importance for stabilization of the knee (1,2). Despite the existing studies examining the timeline and development of the cruciate ligaments in the embryo, there is a paucity of literature describing their position relative to other intra-articular structures and how this may contribute to anatomical variation. Understanding the steps of embryonic and fetal formation of the knee can help elucidate the relationships between the various structures and the resulting clinical conditions. Each developmental stage of the knee is distinguished by morphological criteria that indicate the growth and differentiation of the embryo and fetus (3,4). Studies have found that the developmental orientation of the posterior cruciate ligament (PCL) is intricately linked to the development of other intra-articular structures, including the posterior meniscofemoral ligament (MFL) of Wrisberg (1,5-8). Current studies on the embryological development of the knee include the cruciate ligaments, but to our knowledge there is not yet a review focusing solely on the development of the PCL. The aim of the current review is to create a consolidated perspective on the development of the knee and the cruciate ligaments, bringing together findings and images from various studies that have explored the developing knee by sectioning human embryos and fetuses. This review will also discuss the embryological associations between PCL agenesis and other congenital anomalies.

Embryological development

Human embryonic development can be divided into several stages, or developmental horizons, based on a number of external and morphological criteria shared by each stage. The first seven to eight weeks after conception, or embryonic development, is divided into 23 stages (3). These 23 stages are according to the method of Streeter, which is an adaptation of the Carnegie embryonic staging system (3,9). This staging system based on defined details of developmental structures is more accurate than using the gestational age of the mother’s last menstrual period, creating more standardization and consistency to describe the timing and stages of development. The gestational age of older embryos and fetuses is typically based on the crown-rump length (10).

Stages 13−20

About four weeks after fertilization, at stage 13, the lower limb buds begin to develop and are followed by ectodermal thickening (4). At stage 17, the cartilaginous rudimentary basis of the femur and tibia are separated by cells of a uniform density (10). This uniform interzone is an early sign of cavitation, which is evidence of the beginning of the tibiofemoral joint formation (Figure 1) (9,10). Typically an interzone is seen as the first morphological sign of a joint, however, it is not always essential to joint formation as the femoropatellar articulation forms without an interzonal stage (9). Furthermore, interzones don’t have to continue to joint differentiation, but can also lead to fusion or other processes, such as a tissue invasion. For example, the femorofibular interzone gets invaded by tibial tissue, and it is unclear whether the lateral tibial condylar extension develops as an extension of the tibia or condenses independently and then conjoins with the tibia (2,9).

Figure 1 Knee joint at stage 17 in embryological development, highlighting the early evidence of cavitation of the future tibiofemoral joint. Sagittal section. Goldner ×100. Reproduced from Jarvis et al. (10) with permission obtained. C, cavitation; F, femur; T, tibia.

At stage 18, the ectodermal apical ridge develops along with chondrification at the lower epiphysis of the femur and the upper epiphyses of the tibia and fibula (1,5). Blastemal ends of the femur and tibia create a homogenous articular interzone from which the intra-articular structures will develop along with the joint space itself (11). This is visualized as a single band of mesenchymal tissue (5). At this stage, no intraarticular structures can be identified yet (11,12).

At stage 19, mesenchymal cells begin to condense into the lateral collateral ligament (LCL), medial collateral ligament (MCL), popliteus, and patella (1,10). The peripheral interzone forms the primitive menisci, which are densely packed and darkly stained. In the middle of the interzone facing the intercondylar fossa, precursor cells of the cruciate ligaments loosely assemble into oblique strands, indicating the beginning of the differentiation of future sites of the cruciate ligaments (Figure 2) (1). The gradually distinct primordia of the cruciate ligaments are best seen posteriorly, whereas more laterally the loose layers correspond to the primordia of the menisci (12).

Figure 2 Knee joint at stage 19 in embryological development, highlighting the precursor cells for the cruciate ligaments. All coronal sections, H&E. (A,B) Interzone in the knee joint. (A) ×50, (B) ×100. (C,D) Primordia of cruciate ligaments and menisci. (C,D) ×200. Reproduced from Ratajczak et al. (1) with permission obtained. F, femur; Fi, fibula; I, interzone; T, tibia; A, anterior cruciate ligament; L, lateral meniscus; M, medial meniscus; H&E, haematoxylin & eosin.

At stage 20, the femoral and tibial condyles continue to chondrify, along with differentiation of the LCL, MCL, popliteus tendon, and patellar retinacula (1,10). The patellar tendon begins to form off of the developing quadriceps muscle as it appears the patellar primordium originates in the blastema behind the quadriceps tendon (5,12). At this stage, the nuclear morphology between the patellar cells and the cells in the interzone between the patellar and femur are very similar, whereas the morphology between the patellar cells and the extensor tendon cells are different (12). At this point, the different directions of the anterior cruciate ligament (ACL) and PCL are more apparent, marking the beginning of the distinction between the cruciate ligaments (1). The cruciate ligaments are developed in situ from the intermediate zone of blastema and do not undergo a significant migration event (12-14).

Stage 21 (approximately 7.5 postovulatory weeks)

By this stage, the proximal fibula has already reached its definitive location with respect to the proximal tibia (2). The patellofemoral joint cavity has formed, and the patella is starting to chondrify (1,11,15). The connection joining the lateral condyle and the proximal fibula is maintained via the popliteal tendon by a clump of cells from which the posterolateral structures of the knee will originate (2). The cruciate ligaments are visible and separated by loose connective tissue cells in the interzone. Furthermore, the ACL and PCL cells are oriented in different directions, with the PCL becoming recognizable before the ACL (1,5). The LCL is clearly visible at this stage (2). As seen in Figure 3, the articular interzone of the knee is well-defined, with the tibial and femoral condyles mostly chondrified. The articular interzone between the tibial and femoral condyles was formed by two eccentric bands of mesenchymal tissue, along with a medial band that appears looser and more malleable in relation to the denser eccentric bands (5). There is also evidence that vascularization has begun, specifically in the joint periphery.

Figure 3 Knee joint at stage 21 in embryological development, highlighting the interarticular zone and chondrification of the tibial and femoral condyles. (A) Entire length the fibular collateral ligament can be seen (arrows) (2). Distal section of the pt is in proximity with the FH. (B) Sagittal section (5). Chondrification of the epiphysis of the femur and the tibia, and the first signs of the organization of the condyles are seen. Between the femoral and tibial condyles, the articular interzone begins to form. Scale bar: 50 µm. Reproduced from Oransky and Mérida-Velasco et al. (2,5) with permission obtained. *, common peroneal nerve. M, meniscus; T, tibia; pt, popliteal tendon; FH, fibular head; F, femur; 1, interarticular zone.

Stage 22 (approximately 7.5–8 postovulatory weeks)

During stage 22, the articular cavity appears in the middle and peripheral parts of the femorotibial joint in both the femoromeniscal and meniscotibial compartments (Figure 4) (1). The menisci arise from the eccentric portions of the articular interzone and are contiguous with the cruciate ligaments, though they are not easily distinguishable until week nine of development. The proximal tibiofibular zone appears during this stage, but is not yet clearly established (5).

Figure 4 The knee joint at stage 22 of development, showing where the cruciate ligaments will begin to become more distinguishable. Sagittal section, H&E, ×200. Reproduced from Ratajczak et al. (1) with permission obtained. F, femur; A, anterior cruciate ligament; P, posterior cruciate ligament; T, tibia.

The eccentric layers of the interzone follow the contour of the femoral and tibial condyles and are becoming more organized as they form a dense band of perichondrial connective tissue (Figure 5A) (5,9). Within the same image, the medial layer of the interzone continues to appear looser and more malleable than the eccentric layers. Meanwhile, the lateral parts of the interzone become more condensed, indicating the onset of menisci formation (Figure 5B) (5). The joint capsule begins to form and attach peripherally around the menisci (Figures 5C,6A) (5).

Figure 5 The knee joint at stage 22 of embryological development, highlighting the formation of the menisci. Reproduced from Mérida-Velasco et al. (5) with permission obtained. (A) Coronal section. The articular interzone of the knee appears as a 3 layered structure with two dense eccentric layers leaning against the condyles of the femur and tibia, representing the incoming articular cartilage. Scale bar: 50 µm. (B) Sagittal section. Lateral portions of the articular interzone of the knee form the menisci that are located between the condyles of the femur and tibia. The capsule is attached to the eccentric margin of the menisci. Scale bar: 200 µm. (C) Coronal section. Formation of the meniscofemoral [7] and meniscotibial [8] knee joint cavities has begun. Both cavities are crossed at this time by mesenchymal trabeculae. Scale bar: 100 µm. F, femur; 1, interarticular zone; T, tibia; 3, menisci; 4, knee joint capsule.

Figure 6 The knee joint at stage 22 of embryological development, highlighting the tibial insertion of the PCL and the surrounding loose mesenchyme. Reproduced from Ratajczak and Mérida-Velasco et al. (1,5) with permission obtained. (A) Sagittal view showing chondrification of the patella (P) and the organization of the femoropatellar cavity [6] have begun. The PCL (L) is observed in the medial layer of the knee joint interzone [1]. Scale bar: 200 µm. (B) The intercondylar eminence. Coronal section, H&E, ×100. (C) Coronal view showing the articular zone of the superior tibiofibular joint. At this time, no signs of cavitation is evident. Scale bar: 200 µm. A, ACL; E, intercondylar eminence; F, femur; P, PCL; T, tibia; ACL, anterior cruciate ligament; PCL, posterior cruciate ligament.

On the surface of the tibia, the intercondylar eminence begins to form, and immediately dorsal to this, the tibial insertion of the PCL becomes apparent (Figure 6A,6B) (1,5). The PCL continues dorsoventrally towards the medial aspect of the medial femoral condyle (5). At this point, the cruciate ligaments are surrounded by an area of loosely organized mesenchyme known as the superior tibiofibular interzone, which represents the articulation between the proximal fibula and the lateral aspect of the tibia. No signs of cavitation were present within the superior tibiofibular interzone at this point, with the space instead filled with a network of mesenchymal cells (Figure 6C) (5). Vessels continue to proliferate into the interior of the knee (4).

Stage 23 (approximately 8 postovulatory weeks)

The tibial and femoral shafts begin to ossify and the mesenchymal tissue for the menisci and cruciate ligaments are condensing and becoming more visible (1,11). At this later stage of embryonic development, the menisco-ligamentous complex is well-established, and the knee joint has started to attain a shape similar to that of the adult knee (16). The cruciate ligaments appear as densely packed connective tissue fibers that run longitudinally through the intercondylar notch (Figure 7) (1,2,5). They are still surrounded by loosely organized mesenchyme, but contain more vascular elements running behind them, the most prominent of which include the medial geniculate artery branches (12). There are no vessels in the loose tissue between the menisci and tibia, the menisci and femur, or the femur and patella; these avascular regions will later go on to form the interzones of the future joint cavities (12). The posterior third of the lateral meniscus has now become clearly demarcated from the popliteal tendon by synovial mesenchymal cells (2).

Figure 7 The knee joint at stage 23 of development, highlighting the PCL appearing as more densely packed connective tissue fibers. Sagittal sections, H&E, (A) ×100, (B) ×200. Reproduced from Ratajczak et al. (1) with permission obtained. F, medial condyle of femur; T, tibia; M, medial meniscus; P, posterior cruciate ligament; A, anterior cruciate ligament; PCL, posterior cruciate ligament.

Densification of condylopatellar ligaments was also confirmed by another study (Figure 8) (2). By stage 23, the articular capsule is visible, encapsulating the femoral condyles from the lateral margins of the patella (Figure 7) and attaching to the eccentric surface of the menisci (Figure 9A) (1,17,18). The femoropatellar, femoromeniscal, and meniscotibial joint cavities are well-defined by this stage, while the interzone of the tibiofibular joint is visible but shows no sign of cavitations (Figures 8,9) (2,5,17,18). It is thought that the remnants of the divisions between these joint cavities will go on to form the synovial plicae (11,19). In another study, some specimens showed signs of small joint cavities between some structures, but this observation was not uniformly present. The menisci, interior of the patellar ligament, cruciate ligaments, and posterior joint are vascularized at this point (4,16). The PCL can be seen embedded in the interzone mesenchymal tissue of the knee joint and the patella is more present in medial sections (Figure 9B) (17,18).

Figure 8 Lateral aspect of the human knee joint at stage 23 of embryological development, showing how the relation of the popliteal tendon to the lateral meniscus during development. Lateral aspect of the knee of a human embryo. Reproduced from Oransky et al. (2) with permission obtained. (A) The popliteal tendon (vertical arrow) is adjacent to the entire peripheral margin of the lateral meniscus. Distal portion of popliteal tendon is connected to fibular head. Fibular collateral ligament is posterior to popliteal tendon (horizontal arrow). b, biceps femoris tendon. (B) Intermediate section corresponding to the femoral attachment of the anterior cruciate ligament (white dot). Popliteal tendon is just posterior to the inferior edge of the posterior third of the lateral meniscus. Horizontal arrow points to fibular collateral ligament; vertical arrow points the popliteal tendon which is just posterior to the inferior edge of the posterior third of the lateral meniscus. (C) Medial section corresponding to the posterior horn of the lateral meniscus. Relationship of popliteal tendon (vertical arrow) to the inferior pole of the lateral meniscus (black dot) is shown. In all above sections, mesenchymal stratus of cells separates popliteal tendon from the lateral meniscus. F, femoral condyle; T, tibial plateau; FH, fibular head; M, meniscus.

Figure 9 The human knee at stage 23 of development, depicting how the knee has assumed by this stage a shape akin to that of an adult knee with defined joint cavities. (A) Sagittal section—the quadriceps tendon, the patellar and anterior (A) cruciate ligaments, and the beginning of the patella femoral joint cavitation are outlined. Loose cellular tissue occupies the future site of the infrapatellar fat pad. While the shape of the proximal tibia resembles that of an adult bone, modeling of the femur has not yet started. (B) Sagittal section—the PCL is embedded in the interzone mesenchymal tissue (arrows) of the knee joint. The patella is more present in more medial sections. All sections were stained with haematoxylin and eosin. Photographs were taken using a Nikon Eclipse 80. Reproduced from Finnegan and Kim et al. (17,18) with permission obtained. M, meniscus; F, femur; T, tibia; PT, patellar tendon; FI, fibula; PCL, posterior cruciate ligament.

Stage 23, which extends to the end of week 8, is considered the last stage of embryological development. After week 8 ends, the embryo is considered a fetus for the rest of the pregnancy.

Fetal development

During week 9 of fetal development, cavitations around the femoral condyle and the patella, the femoropatellar, femoromeniscal, and meniscotibial joint cavities, start to coalesce to form larger cavitations (Figure 10A-10D) (2,5,18). Eventually at the end of development, all these cavities will become one to form the adult knee joint, which consists of a single cavity with a synovial lining (11). The septums between the primary joint cavities are noteworthy since its thought that their remnants become the suprapatellar plica and infrapatellar plica. The mediopatellar plica, however, is not a remnant of a septum and is a remnant of mesenchymal tissue. In one study of fetuses aged 11 to 20 weeks, 50% of them had an infrapatellar plica, 33% had a suprapatellar plica, and 37% had a mediopatellar plica (11).

Figure 10 Sagittal sections of interzone mesenchymal tissues of the knee joints of a 9-week fetus. Reproduced from Kim et al. (18) with permission obtained. (A) The ACL is embedded in the interzone tissue remnant (stars) along almost the entire course. The infrapatellar fat pad was not developed (arrow heads). (B) Along the PCL the loose tissue (star) was restricted near the femur. Staining method: haematoxylin and eosin. Photographs were taken using a Nikon Eclipse 80.

At 9 weeks gestation, a mesenchymal band can be seen connecting the proximal end of the patella with the anterior surface of the femur at this point, which may represent the first sign of formation of the fat pad (5,18). Some specimens show a synovial band between the patella and the lateral femoral condyle. The interzone mesenchymal tissue between the tibia and femur are to beginning to disappear at this stage, and most parts of the ACL can be seen embedded in the interzone tissue remnant (Figure 10A) (18). A joint cavitation is advancing into the posterolateral aspect of the joint, and the interzone tissue is merely around the femoral attachment along the PCL (Figure 10B) (5,18). Cavitation also ensues between the popliteal tendon and tibia and continues separating the popliteal tendon and the lateral meniscus (2). A thick band composed of closely packed longitudinally oriented cells is seen connecting the popliteal tendon and fibular head, which demarcates the popliteal bursa posteriorly (2). On the periphery, the menisci can be seen attached by the coronary ligaments to the capsule (5). The development of the infrapatellar fat pad at this timepoint is delayed compared to the cruciate ligaments (Figure 10) (5,18). At certain places, such as the medial aspect of the patellofemoral and the infrapatellar regions, mesenchymal tissue remains and will become the plicae (11).

During weeks 10 and 11 of fetal development, the superior tibiofibular joint cavity appears and has a connection to the meniscotibial joint cavity (5). At this stage, both the lateral meniscus and medial meniscus start to develop more of their final characteristics with the anterior and posterior horns making their attachments (10). As the medial and lateral menisci develop, the menisci are starting to articulate with the femoral and tibial surfaces and form the femoromeniscal and meniscotibial joints (5). The anterior horn of the medial meniscus can be seen attached to the anterior aspect of the upper tibial surface (5). The popliteofibular ligament starts to form, and as the popliteal bursa enlarges, the popliteal tendon detaches from the meniscus and the popliteomeniscal fibers originate (2). At this stage, there are no vascular channels present yet in the epiphyses (10).

During weeks 12–13 of fetal development, the communication between the lateral meniscotibial and superior tibiofibular cavities disappears, and the knee joint cavity starts to attain its final appearance (5). By week 12.5, a dense layer of cells covers the tibiofemoral articular surfaces, and the menisci are well-formed and surrounded by vasculature (10). Vessels can be seen at the periphery of the menisci and vascular channels are present in the femoral epiphysis (10). At this stage, the popliteus muscle can be seen as well as the PCL inserting into the tibia (Figure 11) (10). During week 13, ossification of the knee joint begins starting with the lower epiphysis of the femur and then the upper epiphysis of the tibia (5). Cartilage canals can be seen advancing into the perichondrial zone of the condyles and penetrated from superficial to deep areas (5,10). In the femur, these cartilage canals emerge from the margins and deep portion of the intercondylar notch of the femur (5). In the tibia, the cartilage canals emerge from the anterior and superior margins (5).

Figure 11 Frontal section of a human knee at 12.5 weeks gestation (Goldner, ×20). Reproduced from Jarvis et al. (10) with permission obtained. F, femur; PO, popliteus muscle; PCL, posterior cruciate ligament; LM, lateral meniscus; MM, medial meniscus; T, tibia.

The tibial tuberosity begins to form at 14 weeks, at which point the PCL can be clearly seen on histology inserting into the tibia (10). At this time, the ossification of the patella begins, with cartilage canals emerging from the anterior and superior surfaces (5). There is a thick superolateral attachment of the popliteal tendon to the lateral meniscus, and a fold of the lower aspect of the meniscus can be seen as a vestige at the fascicle that ran between the meniscotibial cavity and popliteal bursa (2). Muscular fascia at the level of the popliteal muscle form a dense fascicle that attaches to the lowest part of the lateral meniscal wall (2).

By week 15.5, the lateral and medial retinacula can be clearly seen, with the medial retinaculum being much denser than the lateral, which helps to distinguish the medial facet of the patella from the lateral facet (10). At the 16^th week of development, the connections between the popliteal tendon, lateral meniscus, and fibular head are fully formed (2). The floor of the popliteal hiatus is formed by an expansion that extends from the popliteal tendon to the lower margin of the lateral meniscus (2). The popliteofibular ligament is fully formed by this point, attaching the posterolateral capsule to the upper fibula via the popliteal tendon (2). The top of the posterolateral capsule is supported by the oblique posterior ligament, which stems from the semimembranosus tendon (2).

One study found a difference in attachment morphology between the ACL and PCL of fetuses at 15- and 16-week gestation (20). Both of the femoral and tibial insertions of the ACL and the tibial insertion of the PCL consisted of a continuation to the perichondrium, indicating that these attachments were not nested in cartilage, but were attached more superficially (20). However, the PCL insertion into the femoral condyle is very deep and has a fibrous tissue mass imbedded in the cartilage (20). It is postulated that this difference in attachments of the cruciate ligaments might be related to the difference in shape, since the femoral condyle is curved and the tibial plateau is flat (20). It has been found previously that ligament attachment morphology changes drastically after birth due to various loading and rotational forces (20-22). After birth, the development of the ACL and PCL is likely to depend on the bipedal posture of humans that requires more stability and less rotation than other animals (20). This leads to a change in the cartilage attachment of the ligaments from a perichondrium-type to a fovea-type from the increased loading force in the knee (20).

By week 16.5, the diaphyseal ossifications of the tibia and femur are progressing towards the metaphyses (10). At this stage of development, the PCL can be seen on histology originating from the intercondylar fossa and the infrapatellar fat pad (Figure 12) (10). The suprapatellar bursa can be seen extending under the quadriceps muscle (10). This is also the stage where blood vessels will begin to cross the growth plate (10).

Figure 12 Sagittal section of a human knee at 16.5 weeks gestation (Goldner, ×5). Reproduced from Jarvis et al. (10) with permission obtained. PCL, posterior cruciate ligament; FP, fat pad; V, blood vessels.

By week 18, the advancing ingrowth of vessels around the tibial tuberosity has begun to separate the apophysis from the tibial epiphysis, and a thick periosteum can be seen spanning from the tibial tuberosity to the tibial metaphysis (10). By week 19, the fat pad is well-developed and the intra-articular structures at the level of the intercondylar notch, including the PCL, are visible (Figure 13) (10). Endochondral ossification of the tibial tuberosity occurs late and does not reach its final destination between the metaphysis and epiphysis until shortly after week 20 (10).

Figure 13 Sagittal section of a human knee at 19 weeks gestation (Goldner, ×20). Reproduced from Jarvis et al. (10) with permission obtained. PCL, posterior cruciate ligament; FP, fat pad.

Clinical relevance

The knee is a complex joint that undergoes many important modifications during the embryological and fetal growth stages, resulting in alterations in joint alignment, shape, and laxity that can last a lifetime (23). The prevalence of abnormalities and normal variants of the knee is unknown, however, the most commonly described variants are the discoid meniscus and bipartite patella that have a prevalence of 2.1% and 1.1% respectively (23). Although rare, reports of congenital anomalies of the PCL have been reported, such as agenesis, and the presence of an accessory bridge between the cruciate ligaments and the lateral meniscus posterior horn (6-8,24-29). Another anatomical variation of the PCL that can be understood with the PCL development is a PCL with a large medial synovial fold that forms a plica (30,31).

Congenital absence of the cruciate ligaments occurs in only 0.017 per 1,000 live births. Most of the documented cases involve ACL agenesis, a few describe both the absence of the ACL and PCL, whereas only three isolated reports of PCL agenesis are found in the literature (6,26). When anatomic variants of the PCL have been reported, most occur related to other abnormalities, such as ACL agenesis, meniscus alterations, patellar dysplasia, thickened MFLs, or hypoplasia of the tibial spines and intercondylar notch (6-8). Thus, this scenario is clinically relevant to distinguish between a chronic PCL tear versus PCL agenesis (8,28,29).

A congenital absence of the PCL is associated with thickened MFLs that have an anterior attachment to the femoral condyle near the PCL footprint, as well as hypoplasia of the tibial spines and intercondylar notch (6-8). An abnormal intercondylar notch that is both narrowed and filled with fibrous tissue has been found to be associated with PCL agenesis (8). Since around stage 21 of embryological development (weeks 7–8) the tibial and femoral condyles develop alongside the cruciate ligaments, the lack of pressure and traction of the cruciate ligaments on the tibial spines and intercondylar notch may lead to lack of development (6,8). Since the purpose of the intercondylar notch is to contain the cruciate ligaments, the development may halt when the cruciate ligaments are missing (8). Without the presence of the developing cruciate ligaments, the normal anatomical reshaping and adaptation process of the notch fails to occur, resulting in a nonfunctional and fibrous intercondylar notch (8).

While case reports of PCL agenesis have described the presence of thickened MFLs, there have been no reported relationships between the embryological development of the cruciate and the MFLs (6,8). Since the lateral MFLs play a role as a secondary posterior knee stabilizer, thickened MFLs may help compensate for the lack of PCL, and explain why patients with PCL agenesis often do not present in the clinic until imaging or arthroscopy following injury to the knee (6,8). In one case report of a patient with isolated PCL agenesis and thickened MFLs, the patient did not have any instability until a low-energy trauma in which the patient sustained a lateral meniscus tear (6). In this patient, the lateral meniscus may have had a role as a secondary stabilizer of the knee and had a larger more important role in knee stability in the absence of the PCL. In another similar case, a patient with congenital absence of both the ACL and PCL, associated with type 1 A fibular hemimelia, had a hypertrophied MFL of Humphrey (27). In another case report, a congenital absence of the cruciate ligaments had the presence of a thickened posterior MFL of Wrisberg (8). Thus, the development of thickened MFLs appears to be in compensation of the lack of cruciate ligaments to help provide more stability to the knee. In the literature, there is no reported connection between the development of the cruciate and MFLs, but this may be due to a paucity of data on the MFLs. Furthermore, their smaller size may cause difficulties in embryological detection before week 10 of development, while the cruciate ligaments may be detected around the 7^th week of development (8).

Since there are clinical implications in distinguishing a chronic PCL tear from a PCL agenesis, it is important to detect signs in the imaging to differentiate the two, since it is possible to have variations in the MFLs without necessarily the absence of the entire PCL (6). A case report of another anatomic variant that is important to distinguish from an injury is one of a bridging accessory bundle connecting the ACL and PCL with the posterior horn of the lateral meniscus (7). This accessory bundle could easily be mistaken for a meniscal fragment (7). In the case of PCL agenesis, there is controversy over the therapeutic approach (8,26,28,29). A systematic review on management for ACL aplasia concluded that reconstruction is an option in only a select number of symptomatic cases and otherwise should be avoided (28). There are not yet any long-term studies on the outcomes of cruciate agenesis, such as the development of osteoarthritis. One study however that looked at 6 cases of PCL agenesis found that it may predispose to meniscus injury, retropatellar pain, or subluxation or dislocation of the knee during leg-lengthening procedures (24). While there have been case reports on the reconstruction of both the cruciate ligaments and isolated ACL in the scenario of agenesis, there have been no reports on isolated PCL reconstruction in a patient with agenesis. Based on the cases of ACL reconstruction for patients with ACL agenesis, some report difficulty with extension and severe patellofemoral pain, while others have reported favorable outcomes. However, the long-term outcomes of these knees are unknown (8,28,29).

Conclusions

This paper consolidates and expands upon findings from different sources throughout the literature to provide a current review of the embryogenesis of the knee, with an emphasis on the PCL. The PCL has received limited attention in the wider discourse on knee development. As such, this review adds to the literature by being the first to focus solely on the development of the PCL. The development of the cruciate ligaments in relation to other intra-articular structures such as the MFLs is discussed, along with the association between embryological development of the PCL and congenital anomalies such as PCL agenesis.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://aoj.amegroups.com/article/view/10.21037/aoj-24-36/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoj.amegroups.com/article/view/10.21037/aoj-24-36/coif). P.J. owns a leadership or fiduciary role in Patella Femoral Foundation, Our Sisters of Mercy Lauralton Hall Academy BOT, and Yale Orthopaedic Alumni BOD. M.J.M. is the consultant of Smith & Nephew and received payment from Depuy Mitek Synthes and Smith & Nephew as the speaker and lecturer. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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