Ehlers-Danlos Syndrome (EDS) is a heterogeneous hereditary connective tissue disorder. The Dutch surgeon Job Van Meek'ren was first described the EDS in 1668, who had observed a 23-year-old man with "extraordinary elasticity of the skin". The term of "Ehlers-Danlos syndrome" refers to a case presentation given by Edward Ehlers and Henry Danlos in 1901 and 1908 respectively. However, a formal description of Ehlers-Danlos syndrome was provided by an English dermatologist, F P Weber in 1936 [1].

Individuals with EDS often exhibit clinical manifestations include joint hypermobility, skin hyperextensibility, and tissue fragility [2]. Additionally, these patients may experience vascular, ocular, and visceral involvement, each associated with specific modes of inheritance [3]. These involvement lead to the symptoms in multiple organ systems including musculoskeletal pain, cardiac manifestations, mast cell activation disorders, Neurological and spinal manifestations, Psychological and Psychiatric problems [4]. Additionally, urogynaecology services symptoms can be exhibit in EDS patients including vaginal prolapse, bladder pain syndrome, recurrent urinary tracts infections [5]. The age range of affected individuals is highly diverse. Previous studies estimate the prevalence of EDS at approximately 1 in 5,000 births, with classical and hypermobile EDS accounting for 90% of cases [6].

EDS is classified into 14 subtypes based on clinical symptoms, including classical EDS, cardiac-valvular EDS, vascular EDS, arthrochalasia EDS, myopathic EDS, classical-like EDS, classical-like EDS type 2, dermatosparaxis EDS, kyphoscoliotic EDS, brittle cornea syndrome, spondylodysplastic EDS, musculocontractural EDS, periodontal EDS, and hypermobile EDS [7]. These types are caused by 20 different gene variants, most of which encode fibrillar collagen types I, III, and V, processing or modifying enzymes, and enzymes that modify the glycosaminoglycan chains of proteoglycans. The causative gene of hypermobile type of EDS remain unknown [8].

Patients with EDS often experience a reduced oral health-related quality of life due to physical pain, psychological issues, and other disabling concerns [9]. Oral and maxillofacial manifestations are common across all types of Ehlers-Danlos Syndrome. Collagen abnormalities compromise oral health, impacting the vascular system, bones, teeth, periodontium, and the neuromuscular and joint systems [10].

Dental issues associated with EDS include fragile oral mucosa, early-onset periodontal defects, unusual missing of the inferior labial and lingual frenum, dental crown anatomy, crown fractures, stunted roots or dilacerations, aberrant dentinal tubules, pulpal vascular pathology and denticles, hypermobile temporomandibular joints (TMJ), and easy movement of teeth in response to orthodontic treatment [11]. Previous studies have revealed decreased bone mineral density in patients with EDS, though the mechanism remains unclear [12]. Eller vainicher et al, also show an impaired bone quality and increased prevalence of vertebral and non-vertebral fragility fractures in EDS patients [13].

The primary medications used in antiresorptive therapy for osteoporosis are bisphosphonates and denosumab (Prolia), which inhibit osteoclast-mediated bone resorption and prevent future fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a very rare side effect of these antiresorptive agents in patients with osteoporosis [14]. Patients with a history of bisphosphonate use who are candidates for orthognathic surgery are at risk of developing MRONJ, which can impede tooth movement [15].

In this study, we present a case of a patient with EDS who had a history of intravenous denosumab injection for the treatment of osteoporosis and subsequently underwent orthognathic surgery to correct dentofacial deformity.

In accordance with the case report (CARE) guidelines [16], this report describes a patient with Ehler Danlos syndrome who had facial deformity. This patient underwent Bimaxillary orthognathic surgery and open septo-rihnoplasty in the Department of Oral and Maxillofacial Surgery at Imam Hossein Hospital.

According to her medical history, she had been diagnosed with Ehlers-Danlos Syndrome (EDS). The patient reported difficulty breathing in an extended head position and exhibited asymmetric breaths. She also had finger joint hypermobility, and clinical dermatological examination revealed soft, velvety, and hyperextensible skin.

In her medical history, the patient reported a facial trauma followed the car accident and then mandibular symphysis fracture and dentoalveolar fracture. In order to treatment, close reduction was performed. (Fig. 1)

the patient mentioned receiving two injections of Prolia 60mg (denosumab) for osteoporosis, the first in May 2021 and the second four months later. Her cardiological examination was unremarkable.

The challenges to orthognathic surgery in this patient included inherent bony abnormalities, a history of denosumab administration, and altered collagen structure, all of which contributed to an unpredictable bone healing process. The patient had been undergoing fixed orthodontic treatment for approximately one year before the consultation for orthognathic surgery.

The patient extra-oral examination in the frontal view revealed a short face, a deep mentolabial fold, and paranasal deficiency. The malar eminences were flat. In the smile view, tooth exposure was minimal, close to zero. The examination of facial lateral view showed a concave profile and mandibular prognathism (Fig. 2).

During the oral examination, it was noted that her inferior labial and lingual frenulum were absent. Additionally, the first maxillary premolar was missing. Her occlusal relationships were Class III on both the right and left sides in the centric position. The maxillary dental midline was shifted 1.1 mm to the right, while the mandibular dental midline and chin midline were deviated 5.3 mm to the right. The reverse overjet measured 11 mm, and the overbite was 2 mm. A posterior crossbite was evident in the right posterior region (Fig. 3).

The temporomandibular joint showed no history of hypermobility or luxation. The patient presented with mild gingivitis but no recession. Pre-surgical orthodontic treatment achieved good intra-arch dental alignment and arch coordination.

Cephalometric analysis revealed a skeletal Class III relationship with maxillary retrusion and mandibular prognathism (Table 1, Fig. 4).

Under general anesthesia and nasal intubation, the patient underwent orthognathic surgery, which included maxillary anterior-inferior repositioning of 4 mm, advancement of 9 mm, and rotation to the left by 1 mm through Le Fort I osteotomy. Mandibular autorotation and a setback of 3 mm were achieved by bilateral sagittal split osteotomy. Maxillary fixation was performed at both the piriform and zygomatic buttresses using miniplates. Mandibular fixation was completed with a trocar and four screws on the right side and a miniplate on the left side.

In December 2023, the patient underwent cosmetic open septo-rhinoplasty. Healing was uneventfully and the results were satisfactory for both the patients and surgeon. (Fig. 7)

EDS are hereditary connective tissue disorders with symptoms such as tissue fragility, skin hyperextensibility, and joint hypermobility, affecting approximately 1 in 5,000 births [17]. EDS results from mutations in collagen-related genes, impacting bone health and leading to conditions like osteoporosis [18]. Patients with EDS may experience reduced bone mineral density, making them susceptible to fractures, which is managed with antiresorptive drugs such as bisphosphonates and denosumab [12].

Oral and maxillofacial issues in EDS patients include TMJ instability, fragile oral mucosa, early periodontal disease, and abnormal dental anatomy [11]. These factors complicate surgical procedures, raising concerns about delayed healing and postoperative complications [19]. However, recent studies suggest that orthognathic surgery can be safely performed in EDS patients, even those on bisphosphonate therapy. For example, research by Arnaud Gleizal found that patients on bisphosphonates experienced normal bone and mucosal healing without osteonecrosis or periodontal issues [20]. Similarly, Tengku Shaeran and colleagues reported successful bimaxillary surgery in a patient with a history of oral bisphosphonates by incorporating a drug holiday [21].

In this case, the patient with EDS and a history of intravenous denosumab underwent successful bimaxillary orthognathic surgery. Despite concerns about collagen synthesis affecting bone healing, the surgery was completed without major complications, demonstrating that with careful planning, such surgical interventions can be effectively managed in EDS patients.

This case demonstrates that with careful planning, bimaxillary orthognathic surgery can be successfully performed in patients with EDS, even those with a history of denosumab administration. Despite the challenges of altered collagen structure and bone healing, the patient experienced a smooth recovery with no major complications, highlighting the potential for effective surgical correction of dentofacial deformities in EDS patients.