Full-Mouth Rehabilitation With Implant-Prosthesis in Marfan Syndrome Patient: Clinical Report and Literature Review

Marfan syndrome is a genetic disorder that affects connective tissues throughout multiple areas of the body, including the heart, bones, joints, and eyes. The physical manifestations of this syndrome were first reported by Marfan in 1896, who described the case of a 5-year-old girl who presented with long, slender digits and multiple skeletal abnormalities.¹  It was not until the 1950s that Marfan syndrome was discovered to be a connective tissue disorder.²  Marfan syndrome is an autosomal dominant disorder with mutations in the FBN1 gene.³  The FBN1 gene, located on chromosome 15, encodes fibrillin-1, an important protein in the extracellular matrix in connective tissues. Any deficiency in fibrillin-1 affects the resiliency of tissues to stress.⁴ 

The diagnosis of Marfan syndrome was traditionally based on clinical criteria and family history.^5,6  However, wide variations in the clinical presentation led to discrepancies of the diagnostic criteria. The introduction of Ghent-1 criteria^7,8  in 1996 helped create major and minor diagnostic features of the syndrome^9,10  and decreased the risk for missing a diagnosis using traditional diagnostic criteria.¹¹  These criteria include information gathered from medical history, clinical examination, family history, genetic testing, and cardiovascular imaging.⁵  The diagnosis is based on a combination of clinical manifestations, cardiac findings, and genetic findings (mainly FBN1 gene mutation). The manifestations assessed include, but are not limited to, aortic root enlargement, ectopia lentis, and a pathogenic FBN1 variant.⁵  Additionally, a number of highly variable skeletal, ocular, and cardiovascular signs can be observed. Ghent-2 criteria were recently introduced to reprioritize the signs and symptoms, facilitating the early diagnosis of cardiovascular complications.⁹ 

The reported incidence of Marfan syndrome varies between 1 and 7 cases in 10 ,000 worldwide.^5,12,13  A much lower incidence (6.5 cases in 100 ,000) was reported in Denmark in 2015 using the Ghent-2 diagnostic criteria.¹⁴  Many cases are confirmed during the first two decades of life due to the striking clinical manifestations.

The connective tissue abnormality affects multiple organ systems in the body. The major musculoskeletal manifestations of Marfan syndrome are shown in Table 1, and the ocular, cardiovascular, and oral manifestations are described in the sections that follow.

The hallmark ocular change of Marfan syndrome is bilateral dislocation of the lens (ectopia lentis).²  It is estimated that ectopica lentis affects up to 60% of patient with Marfan syndrome.⁵  Additionally, patient with Marfan syndrome have a high incidence of spontaneous retinal detachment²  and myopia.^2,5 

Cardiovascular complications cause up to 95% of deaths in patients with Marfan syndrome.^7,8  However, with proper management, life expectancy approaches that of the general population.⁵  Cardiovascular malformations include interatrial septal defects,²  weakness of the media of the aorta and pulmonary artery,²  and dilation of the aortic root.⁵  The latter is common and could lead to aortic dissection, which is the most common cause of death in patients with Marfan syndrome.²³ 

In addition to the aforementioned craniofacial manifestations, multiple oral and dental manifestations are observed in patients with Marfan syndrome. Table 2 focuses on the common oral manifestations, while the following sections place particular emphasis on the periodontal tissues in patients with Marfan syndrome.

The syndrome is characterized by a narrow nasal airway, which leads to mouth breathing,¹⁷  thereby increasing the risk of developing obstructive sleep apnea.³⁰  Both adults and children with Marfan syndrome have a higher prevalence of obstructive sleep apnea than matched controls,^31,32  with a reported prevalence of up to 64%.³⁰  Correction of Class II malocclusion can improve nocturnal breathing.^32,33  This can be achieved by a combination of treatments, including rapid maxillary expansion or mandibular advancement devices.³²  Although the apnea-hypopnea index and oxygen desaturation index remain higher in children with Marfan syndrome, even after treatment with rapid maxillary expansion, a study found that children treated with mandibular advancement showed no significant differences compared with control children.³²  On the other hand, rapid maxillary expansion in patients with Marfan syndrome resulted in a significant reduction in the horizontal airway dimensions and a significant increase in the vertical airway dimensions compared with control patients. Mandibular advancement did not affect these dimensions significantly.³²  These findings suggest that the combination of these 2 treatment methods improve the prognosis of obstructive sleep apnea in patients with Marfan syndrome.

Contradictory evidence has been reported regarding periodontal disease in patients with Marfan syndrome; some studies report severe periodontal disease,^27,34,35  while another multicenter study does not.³⁶  There is more evidence to support the increased incidence and severity of periodontal disease in patients with Marfan syndrome.²⁷ 

In one study, 87.5% of patients with Marfan syndrome suffered from periodontitis and had fewer teeth than a control group.³⁷  Another study compared patients with cardiovascular disease with or without Marfan syndrome and reported that those with Marfan syndrome suffered from periodontitis more frequently and with greater severity.³⁸  Mutations in FBN1 encoding fibrillin are typically present in patients with Marfan syndrome. Fibrillin is a major component of the elastic fibers that have a mechanical function within the periodontal ligament; therefore, it has a strong impact on the periodontal ligament.^39,40 

Fibroblasts from a patient with Marfan syndrome were isolated and immortalized. The cells were found to be associated with irregular microfibril assembly compared with cells from a healthy control participant, suggesting a role for FBN1 in regulating cell alignment and microfibril assembly.⁴¹  It is suggested that wild type fibrillin-1 encoded by this gene is essential for cell alignment and tissue architecture in periodontal ligaments.⁴²  Cells from the patients with Marfan syndrome also expressed a higher level of activated TGF-β than the healthy control, suggesting the importance of TGF-β activation in the pathogenesis of Marfan syndrome.⁴¹  It is therefore speculated that TGF-β can be a target for therapy and prevention of cardiovascular and periodontal complications.³⁸  Despite the wide range of oral manifestations of Marfan syndrome, none of these manifestations were included as diagnostic criteria in the Ghent system.¹⁰ 

Marfan syndrome is a complex disorder with multiple manifestations affecting various systems. Therefore, multidisciplinary management is essential.⁴³  Because of intraoral findings, patients with Marfan syndrome should be referred to an orthodontic clinic more readily than healthy individuals.⁴⁴  The variability of clinical features of Marfan syndrome creates difficulties in early diagnosis. For this reason, dental professionals may be the first health care providers to observe and refer these patients for initial diagnosis. The role of general dental practitioners and orthodontists is of particular interest as they can identify multiple manifestations of this syndrome and significantly contribute to the management and prevention of associated complications. In particular, dentists should identify signs associated with Marfan syndrome, such as skeletal Class II malocclusion, joint hypermobility, periodontal inflammation, lip incompetence and craniofacial deformities,⁴³  and obstructive sleep apnea.

The dental team should manage periodontal inflammation, correct malocclusions and occlusal discrepancies, and monitor craniofacial growth.⁴³  Prevention is of paramount importance in patients with Marfan syndrome. Thus, the appropriate periodontal routine should be chosen (prophylaxis or scaling and root planning) to reduce periodontal inflammation and decrease the risk of endocarditis.⁴³ 

Due to cardiovascular complications in patients with Marfan syndrome, consideration should be given to anesthesia and prophylactic antibiotic coverage. Dental treatments, in particular extractions, are often carried out under antibiotic prophylaxis.^{11,17,18,22,45,46}  Treatment modalities of oral and dental manifestations vary depending on each individual.

In the case of a 12-year-old patients with Marfan syndrome whose demonstrated protrusion of maxillary anterior teeth, impacted maxillary canines, and posterior crossbite,¹⁸  periodontal treatment was performed to improve gingival status. Oral hygiene instructions were emphasized before orthodontic treatment was started. The patient was prescribed prophylactic amoxicillin before orthodontic banding, periodontal treatment, or tooth extraction.¹⁸ 

A 56-year-old woman with Marfan syndrome has been seen since 1999 in the periodontal clinic. Her medical history revealed controlled hypertension and mitral valve prolapse. She is currently taking the following medications: metoprolol 50 mg, losartan 50 mg, Claritin, acidophilus, calcium, and Nexium. During the previous 20 years, she had extensive dental treatment in an attempt to restore and maintain the teeth for as long as possible (restorations, extractions, and periodontal maintenance were performed). The amount of bone loss over the years and malocclusion led the patient to desire an implant-supported prosthesis to replace the entire dentition for better esthetics and function (Figure 1).

Several treatment plan options were discussed with patient as well as the type of prosthesis (fixed vs removable) and support (tissue vs implant). The patient chose implant-retained overdentures due to the ease of implant hygiene, superior esthetics (flange support to enhance the lips and cheeks), and decreased cost compared with full-arch implant-supported restorations. Implant-retained overdentures increase stability and retention of the dentures in advanced bone resorption cases. This patient was classified as Cl-IV based on the prosthodontic diagnostic index due to severely compromised dentition and ridge resorption.

The treatment plan started with bilateral maxillary sinus grafting procedures under intravenous sedation (Figure 2). The periodontist completed a lateral window sinus lift procedures using Piezosurgery, minimizing the incidence of Schneiderian membrane perforation. The maxillary sinus was grafted with a mixture of bone morphogenetic protein-2, Xenograft, and Allograft particulate. The lateral window osteotomy was covered with a resorbable collagen membrane.

After sinus augmentation, uneventful healing was observed for 9 months. Full-mouth extraction was performed, and core bone samples were retrieved from the middle of the bilateral sinus window sites. Histologic examination was completed to assess the quality of the bone in the grafted sinus (Figure 3). Alveoloplasty of the alveolar ridge was performed. A total of 9 regular neck SLActive Straumann implants were immediately placed in sites 3, 5, 6, 12, 14, 22, 24, 26, and 27 (Figure 4).

Immediate maxillary and mandibular complete overdentures were delivered for function while waiting for complete osseointegration of dental implants. The patient was regularly observed to ensure establishment of adequate stability and hygiene. After 4 months of healing, the dental implants were successfully osseointegrated, and Locator abutments were inserted. Metal-reinforced complete maxillary and mandibular overdentures were fabricated using conventional denture fabrication methods. An intraoral pickup of the implant attachments to the final prostheses was completed using Quick-Up material (Figure 5).

Twenty-four months after final prostheses delivery, the patient continued to function with satisfactorily stability and retention. The maxillary sinus augmentation outcome was successful, and the implants maintained osseointegration.

To our knowledge, implant-retained full-arch prostheses have not been reported in a patient with Marfan syndrome. Interestingly, defective collagen metabolism has been associated with decreased bone volumes and lower bone to implant contact.⁴⁷  While other collagen disorders have similar presentations (lathyrism and multiple sclerosis), there is no evidence regarding the effect of Marfan syndrome on the osseointegration of dental implants.

A case report in 2010 discussed the use of implant-supported prosthesis in a patient with Marfan syndrome. The 20-year-old male patient presented with Class III malocclusion, missing teeth in both jaws, high-arched palate, and a thin knife-edged mandibular ridge. Mandibular teeth were extracted, and surgery was performed to place 7 implants in the edentulous mandibular ridge. Upon healing, a ceramo-metal prosthesis was fabricated (tooth retained in the maxilla and implant retained in the mandible). After 6 months, the implant-retained prosthesis was in excellent condition, and the patient was satisfied with comfort and function.⁴⁸ 

In our patient, the implants appeared to maintain osseointegration after 3 years' function. The implants supporting the prostheses showed no signs of peri-implant disease, and implant failure has not occurred.

After sinus augmentation, implant integration, and delivery of the implant-retained prostheses, the patient is functioning well with no major complications. For patients with Marfan syndrome, implant-retained prostheses prove to be a highly effective treatment option. The role of dental care professionals in the management of patients with Marfan syndrome is key for improving the quality of life for these patients.

Abbreviation

FBN1:

fibrillin-1

The authors report no conflicts of interest.