Introduction
Hereditary abnormalities involving connective tissue are among the most common genetic diseases in human beings. Individuals with these disorders demonstrate an array of disease severity and phenotypes, and athletes with these disorders are at increased risk of anterior cruciate ligament (ACL) injury. Surgery to reconstruct the ACL in these patients is associated with a significantly increased risk of complications, and special consideration must be given to all facets of orthopaedic care in an effort to achieve an optimal outcome. In this chapter, we will focus primarily on those heritable disorders of connective tissue that are commonly encountered by surgeons performing ACL reconstruction for which there is some discussion in the existing orthopaedic literature. These disorders include osteogenesis imperfecta (OI), Ehlers-Danlos syndrome (EDS), and Marfan syndrome (MS).
Body
Osteogenesis Imperfecta
OI is a heritable disease of connective tissue that results from mutations in one of the two genes that code for type 1 procollagen, and it is generally characterized by bone fragility. When taking care of patients with this disease, it is important to recognize that any connective tissue related to type 1 collagen may be affected. In addition to bone fragility and multiple fractures, patients with this disorder commonly exhibit pronounced ligamentous laxity, blue sclera, dental abnormalities, spinal and long bone deformity, progressive hearing loss, skin that scars extensively, and cardiovascular manifestations. Diagnosis is usually made on the basis of clinical criteria. The most commonly used classification was developed by Sillence ( Table 125.1 ) and highlights the variability of the disease and its manifestations. Genetic testing is available, although it is often performed only at specialized centers.
| Type | Bone Fragility | Blue Sclera | Abnormal Dentition | Hearing Loss | Inheritance |
|---|---|---|---|---|---|
| I | Mild | Present | Absent in IA Present in IB | Present in most | Autosomal dominant |
| II | Extreme | Present | Present in some | Unknown | Autosomal recessive or sporadic |
| III | Severe | Bluish at birth | Present in some | High incidence | Autosomal dominant or recessive |
| IV | Variable | Absent | Absent in IVA Present in IVB | High incidence | Autosomal dominant |
Ehlers-Danlos Syndrome
EDS is a group of heritable disorders characterized by hyperelasticity of the skin and hypermobile joints. It has been classified into six major types, and specific mutations have been described for most types ( Table 125.2 ). The preponderance of cases falls into the classical and hypermobile types with vascular being the third most common. Often patients manifest characteristics of varying types and may not fit perfectly into one classification. In addition to hyperelastic skin and hypermobile joints, EDS is also commonly associated with visceral involvement, bleeding, pain syndromes, scoliosis, ophthalmologic abnormalities, and neuromuscular involvement. The clinical course can vary from severe cases to mild or moderate forms.
| Type | Major Criteria | Minor Criteria | Inheritance | Genetic Defect |
|---|---|---|---|---|
| Classical | Skin hyperextensibility, widened atrophic scars, joint hypermobility | Smooth skin, molluscoid pseudotumors, subcutaneous spheroids, joint hypermobility, easy bruising, tissue fragility, positive family history | Autosomal dominant | Abnormal type V collagen ( COL5A1 and COL5A2 genes) |
| Hypermobility | Skin involvement, generalized joint hypermobility | Recurrent joint dislocations, chronic limb pain, positive family history | Autosomal dominant | Reduction in tenascin X (small percentage of cases) |
| Vascular | Thin skin, arterial intestinal or uterine fragility, extensive bruising, characteristic facial appearance | Acrogeria, small joint hypermobility, tendon or muscle rupture, clubfoot, early onset varicose veins, arteriovenous fistulae, pneumothorax, gingival recession, positive family history | Autosomal dominant | Structural defects of type III collagen ( COL3A1 gene) |
| Kyphoscoliosis | Generalized joint laxity, severe muscle hypotonia, scoliosis, scleral fragility | Tissue fragility, easy bruising, arterial rupture, Marfanoid habitus, microcornea, osteopenia, positive family history | Autosomal recessive | Deficiency of lysyl hydroxylase (collagen modifying enzyme) |
| Arthrochalasia | Severe joint hypermobility with subluxations and congenital hip dislocations | Skin hyperextensibility, tissue fragility, easy bruising, muscle hypotonia, kyphoscoliosis, osteopenia | Autosomal dominant | Deficiency of chains in type I collagen (skipped exon 6 in COL1A1 or COL1A2 genes) |
| Dermatosparaxis | Skin fragility, redundant skin | Soft skin, easy bruising, premature rupture of fetal membranes, umbilical or inguinal hernias | Autosomal recessive | Deficiency of procollagen I ( ADAMST2 gene) |
Marfan Syndrome
MS is a heritable disorder of connective tissue that results from a mutation in the fibrillin gene. It is characterized by three dominant features: skeletal changes (long, thin extremities, arachnodactyly, chest deformities, scoliosis, and high pedal arches or pes planus), reduced vision (due to ectopia lentis), and aortic aneurysms. Diagnosis is usually made on the basis of clinical criteria (identification of the above features). Milder forms that predominantly result in only the skeletal manifestations of the disease exist and are difficult to classify. Any patient suspected of having MS should have a slit lamp examination and echocardiogram to rule out ocular and cardiac abnormalities. Genetic testing is available and may be useful in some cases, but is not mandatory to establish the diagnosis.
Clinical Evaluation
ACL injury occurs in this population and is difficult to successfully treat. Common features of heritable connective tissue disorders include osteoporosis, ligamentous laxity, and elastic or fragile skin, all of which could negatively affect the outcome following ACL reconstruction. Even more importantly, we must remember that patients who present to us with the musculoskeletal manifestations of these diseases may also have less identifiable and possible life-threatening associated conditions that require referral and appropriate workup. In our experience, connective tissue diseases often present as a spectrum of phenotypes, and care and treatment strategies must be individualized. However, due to the complex nature of these diseases, we find it helpful to follow a standardized approach to all patients suspected of having a connective tissue disease. In this section we will discuss the clinical evaluation, surgical treatment, and rehabilitation of ACL injury in this population of patients.
History
A detailed understanding of the mechanism of injury is quite helpful. Lower energy mechanisms or atypical injury patterns are more common in this population and may provide some insight as to the severity of the underlying disorder. A complete past medical history is essential. This should focus on fracture history; abnormal bleeding or scarring; previous joint laxity or dislocations; cardiovascular, visual, or dental problems; abnormal healing; and any history of chronic pain. Additionally, because these diseases are heritable, patients should also be asked whether any family members exhibit the above signs or symptoms.
Physical Examination
Many patients with heritable connective tissue diseases exhibit joint hypermobility of varying degrees, and it is often difficult to determine which condition they may have based on their hypermobility. The literature is not clear, and disorders like benign joint hypermobility syndrome, hypermobility type EDS, and generalized joint hypermobility are difficult to differentiate. To avoid confusion and to ensure appropriate attention is placed on both the symptoms from hypermobility as well as those related to other manifestations of connective tissue disorders, it is helpful to assign the diagnosis joint hypermobility syndrome to all patients with symptomatic joint hypermobility, in addition to any contributing connective tissue disorder. Beighton score is useful for the assessment of joint hypermobility and allows for some characterization of the severity ( Table 125.3 ). Often heritable connective tissue disorders are relatively easy to recognize based on their typical features, including abnormal faces, dentition, scarring, or stria; blue sclera; and deformity of the long bones, spine (scoliosis or kyphosis), hands (arachnodactyly), feet (pes planus, or high pedal arches), or chest. Cardiac evaluation should be performed to identify any associated valve or vessel abnormalities (aortic dilations and mitral valve prolapse are common).
| Finding | Score |
|---|---|
| Passive apposition of the thumb to the flexor aspect of the forearm (one point for each hand) | 2 |
| Passive dorsiflexion of the fifth digit beyond 90 degrees (one point for each hand) | 2 |
| Hyperextension of the elbow beyond 10 degrees (one point for each arm) | 2 |
| Hyperextension of the knees beyond 10 degrees (one point for each leg) | 2 |
| Forward flexion of the trunk with the knees extended, while the palms easily rest flat on the floor | 1 |
Additional Testing
A genetics consultation is typically ordered for patients with Beighton scores greater than 5, those with a positive family history of a connective tissue disorder, those who exhibit other pathognomonic signs of a heritable connective tissue disorder, and those with any history of family history of artery or visceral rupture. Due to the association of cardiac abnormalities and heritable connective tissue diseases, echocardiogram and primary care or cardiology evaluation of all patients is recommended. Ophthalmology consultation is obtained for all patients with a confirmed heritable connective tissue disorder or who exhibit joint hypermobility and visual symptoms. In addition to the standard imaging modalities commonly used in the assessment of patients with ACL injury, dual-energy X-ray absorptiometry (DEXA) can be helpful to quantify the degree of decreased bone mineral density in this patient population. Atypical pain patterns are associated with these disorders, and anesthesia pain management assessment and intervention can be helpful prior to any intervention, particularly for patients who exhibit pain out of proportion to their physical or imaging findings.
Surgical Reconstruction
ACL surgery in patients with connective tissue disorders results in a higher rate of complications when compared with surgery performed on unaffected individuals. In this section we will discuss several considerations that may help mitigate some of this risk.
Perioperative Considerations
As discussed previously, a cardiovascular evaluation with echocardiogram and assessment for bleeding disorders should be performed prior to surgery. Prophylactic antibiotics should be given as indicated, and all patients should have a blood type and screen in case abnormal bleeding is encountered and transfusion is necessary. Attention must be paid to positioning in order to prevent abnormal pressure on skin or injury, subluxation, or dislocation of another joint. Intubation needs to be performed carefully to avoid iatrogenic damage to the soft tissues in the mouth and throat. High airway pressures may result in barotrauma to the lung tissue, or pneumothorax and hypertension should be avoided to prevent damage to blood vessels.
Surgical Considerations
The bleeding abnormalities associated with connective tissue diseases increase the risk of hematoma formation postoperatively, and electrocautery is utilized to maintain meticulous hemostasis. In general a tourniquet is avoided to decrease the risk of vessel rupture and to enable the identification of small vessels that may bleed. Care should be taken when drilling tunnels and placing implants to decrease the risk of iatrogenic fracture. The surgeon can also take this opportunity to get a sense of the degree of osteopenia, and backup fixation may be considered. Graft choice in this patient population is controversial, and there is no clear guidance from the available published literature. At first look, allograft may seem to be appropriate, as this avoids utilizing the patient’s own connective tissue that is known to be compromised. However, evidence shows that re-rupture rates in the general population may be higher with allografts, and in patients with connective tissue disorders, this rate could be even higher due to a more disordered process of ligamentization. Healing is abnormal in this population, and it is likely that graft incorporation may be adversely affected. Bone–tendon bone–autograft and double-bundle quadriceps autograft have been successfully used for patients with generalized ligamentous laxity. There are no reports of large series of allograft reconstruction in this patient population. Using autograft must be weighed against the risk of iatrogenic fracture or failure of donor tissue (quadriceps or patellar tendon rupture) due to further weakening already abnormal structures. Patients with OI in particular are at risk for future fractures and may be more difficult to treat if they occur in the area of the previous donor site. For most patients (those with sufficient bone and tendon size/quality), our graft of choice is bone–patellar tendon–bone autograft; however, further study is necessary to identify the optimal graft type. ACL graft fixation can be performed many different ways. Due to disordered healing and incorporation, we avoid biologic fixation and typically utilize metal interference screws (biologic screws are used for soft tissue grafts to decrease the risk of graft damage). Intermittent parathyroid hormone to enhance biologic healing potential and incorporation of the graft can be considered but is unstudied in this patient population. Depending on bone quality, fixation may be backed up on the femur or tibia with a screw and post. Due to abnormalities within the connective tissue of the skin, wound-healing problems are more common in this patient population. Unnecessary retraction should be avoided, and a careful layered closure must be performed. We generally utilize nylon sutures over bioabsorbable products and reinforce the closure with Steri-Strips. The patient may require more frequent checks postoperatively, and often sutures are left in place for an extended period (14–21 days). For most patients, immobilization in a brace is also extended 2 additional weeks to allow for enhanced wound healing. Pain is common, and multimodal pain management is helpful. Nonsteroidal antiinflammatory drug use is avoided if at all possible during the initial 6 weeks postoperatively to avoid its potential detrimental effect on healing in an already compromised host. Vigilance should be maintained for the development of complex regional pain syndrome, and pain management consultation should be expedited if there are any concerns.
Postoperative Rehabilitation
Physical therapy (PT) following surgery begins during the first postoperative week. We feel this frequent contact facilitates the early identification of any complications and allows us to individualize the patient’s rehabilitation. PT modalities and desensitization techniques may be helpful in alleviating early postoperative pain. Typical ACL reconstruction is phase based. In addition to prolonged healing rates, many patients with connective tissue disorders exhibit some degree of neuromuscular involvement. Due to these factors, rehabilitation is more prolonged in this patient population, and there is a greater amount of time spent in each phase of recovery. Most patients are counseled to expect a minimum 12-month recovery. Support groups are available for patients with heritable connective tissue diseases and include the Osteogenesis Imperfecta Foundation ( www.oif.org ), the Ehlers-Danlos National Foundation ( www.ednf.org ), and the Marfan Foundation ( www.marfan.org ).
Case Example
A case of a patient with ACL tear and OI is presented to highlight some of the unique considerations a surgeon faces when treating patients with heritable connective tissue disease.
A 24-year-old male golfer with previously diagnosed type IA OI slipped on a wet floor and experienced a valgus extension injury to his left knee, tearing his ACL. Past medical history was significant for gastroesophogeal reflux disease (GERD) and fractures of his left femur and tibia, three vertebral compression fractures, and a right humerus fracture. His most recent fracture was 4 years prior to presentation. He denied previous wound or fracture healing problems and had no history of dental, hearing, visual, or cardiovascular problems. Family history was significant for OI in his father and one sister. DEXA scan was performed and demonstrated severe osteoporosis in both the spine and appendicular skeleton. The patient remained symptomatically unstable following a period of nonoperative treatment and desired ACL reconstruction.
ACL reconstruction was performed using anterior tibial tendon allograft. Allograft was chosen for this patient due to his severe osteoporosis, in an effort to avoid the risk of iatrogenic fracture or postoperative fracture to the patella or patellar tendon rupture. Graft fixation of the tibia was with an interference screw, and graft fixation on the femur was with an interference screw backed up by a screw and washer due to poor bone quality around the femoral tunnel.
The patient was non-weight-bearing for 10 days and immediately began knee range of motion and quadriceps strengthening. He progressed to full weight bearing at 4 weeks. He had a delayed return of full quadriceps strength, but by 1 year his quadriceps bulk and tone were comparable to the contralateral thigh. He resumed golf at 6 months. He did not participate in any cutting or contact sports. Postoperative images 27 months and 14 years following surgery are displayed in Fig. 125.1 . Since his reconstruction, he has sustained a patella fracture and tibial shaft fracture in operative extremity.
Related posts:
Risk of Anterior Cruciate Ligament Injury as a Function of Type of Playing Surface
Hamstring Harvest Technique for Anterior Cruciate Ligament Reconstruction
Femoral Tunnel Creation Using the Zimmer Biomet SwitchCut Femoral Aimer
Cortical Screw Post Femoral Fixation Using Whipstitches, Fabric Loop, or Endobutton: The Universal Salvage
Acute Anterior Cruciate Ligament Rupture: A Biological Approach through Primary Anterior Cruciate Ligament Repair, Augmentation with Bone Marrow Stimulation, and Growth Factor Injection
Allografts Have Higher Failure Rates Than Autografts in Anterior Cruciate Ligament Reconstruction in Young, Active Patients
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
