Worth Syndrome-Patient Report, Diagnostic Work-Up, and Surgical Management of a Rare Craniofacial Entity.

Worth syndrome is a rare genetic bone disorder that often presents with cortical thickening of the mandible and an increase in mandibular width. The authors report the preoperative considerations in a young female with Worth syndrome, operative planning, and successful mandibular reduction using cutting guides.

A successful implant-supported fixed prosthesis in a patient with osteopetrosis: A clinical report.

Osteopetrosis (marble bone disease) is a family of rare genetic disorders characterized by impaired osteoclast function leading to hyperdense, hypovascular, brittle bone. Typical imaging shows increased bone mass and thickened cortical and trabecular bone. Bones are more prone to fracture and osteomyelitis may develop. When considering dental implant placement in a patient with osteopetrosis, the potential for bony fracture and/or osteomyelitis should be considered along with the decreased likelihood of successful osseointegration because of hypovascularity. This clinical report describes an unusual imaging presentation and successful osseointegration of multiple dental implants supporting an implant-supported fixed mandibular prosthesis with long-term survival.

Successful complete oral rehabilitation of a patient with osteopetrosis with extensive pre-treatments, bone grafts, dental implants and fixed bridges: a multidisciplinary case report.

BACKGROUND: Osteopetrosis comprises a group of inherited disorders that are rare and result in abnormal bone structure. Bone remodeling is extremely inhibited because osteoclasts are nonfunctional or lacking. This condition causes overgrowth of bone with disappearance of the bone marrow, leading to aplastic anemia; obstruction of nerve passages in the skull leads to blindness and often hearing impairment. In most cases, osteopetrosis results in oral complications such as tooth deformation, hypomineralization, and delayed or absent tooth eruption. The only curative treatment is hematopoietic stem cell transplantation (HSCT). The main treatment of the oral complications during childhood and adolescence consists in protecting the erupted teeth against caries disease through prophylactic treatment aimed at optimal oral hygiene through frequent regular dental visits throughout life. Many patients with osteopetrosis require major oral rehabilitation to treat complications of the disease. Improved results of HSCT increase the likelihood that dental professionals will encounter patients with osteopetrosis. CASE PRESENTATION: In this case report, we show that individuals with osteopetrosis who have severe oral complications can be treated successfully if they are treated for osteopetrosis at an early age. The boy had his dental care in pedodontics, and regular multidisciplinary meetings were held for future treatment planning. At the age of 15, he was then referred for rehabilitation. The initial evaluations revealed no further growth in the alveolar bone. The rehabilitation was done stepwise, with extraction of malformed and malpositioned teeth. Initially, the patient received a removable partial denture followed by reconstruction of the width of the alveolar process, titanium implants, temporary fixed bridges, and finally screw-retained titanium-ceramic bridges with titanium frames for the upper and lower jaws. CONCLUSIONS: The three-year follow-up after loading indicated a stable marginal bone level and optimal oral hygiene as a result of frequent professional oral hygiene care. The patient showed no signs of symptoms from the temporomandibular joint and has adapted to the new jaw relation without any functional or phonetical issues.

[Minimally Invasive Direct Coronary Artery Bypass in a Patient with Osteopetrosis and Symptomatic Ischemic Heart Disease:Report of a Case].

Osteopetrosis is a heterogeneous group of heritable conditions. It varies greatly in severity, and fracture treatment remains a matter of controversy due to altered responses to fixation and the risk of osteomyelitis. Therefore, sternotomy outcomes in this condition are unclear. We report the case of a patient with osteopetrosis and coronary artery disease (CAD). A 78-year-old man with osteopetrosis presented with frequent chest pain. Coronary angiography revealed two-vessel CAD. Percutaneous coronary intervention was contraindication because of coronary aneurysm in the left main trunk. Considering risks in median sternotomy, we performed minimally invasive cardiac surgery through left minithoracotomy for coronary artery bypass grafting( CABG). But we needed to break the left fourth rib to obtain sufficient surgical views. To the best of our knowledge, this is the first case report on CABG for a patient with osteopetrosis and endoscopic surgery without rib retractor is recommended.

Anterior cruciate ligament rupture in a patient with Albers-Schonberg disease.

BACKGROUND: Osteopetrosis is an uncommon inherited disease marked with elevated bone density and frequent bone fractures owing to flawed osteoclast activity. Autosomal dominant osteopetrosis type 2 (ADO-2), a benign form of osteopetrosis, is also known as Albers-Schonberg disease. CASE PRESENTATION: We report the first successful anterior cruciate ligament (ACL) reconstruction surgery for ACL rupture treatment in a 30-year-old female with ADO-2, who carried a heterozygous missense mutation c.2227C > T (p.Arg743Trp) in exon 23 of the chloride channel 7 (CLCN7) gene. Histopathological analysis of the ruptured ACL sample revealed massive calcium salt deposition in the ligament tissue. A ligament advanced reinforcement system (LARS) artificial ligament was employed in her ACL reconstruction surgery. At her final 16 month's follow-up, she reported no knee instability symptoms and other complications. The range of motion of the affected knee was good. The side-to-side difference in knee laxity, as evidenced by a KT-1000 arthrometer was 0.9 mm. The Lysholm score improved from 45 before operation to 83 after operation. The Tegner activity score improved from 1 before operation to 4 after operation. CONCLUSIONS: Our findings further confirmed that the newly identified mutated locus (p.Arg743Trp) may lead to acid secretion disorders at different sites (including calcified ACL in our case). In terms of clinical treatment, ligament reconstruction surgery in patients with Albers-Schonberg disease presents a unique challenge to orthopedic surgeons and requires further preparation and time.

Total Hip Arthroplasty in Patients With Osteopetrosis.

BACKGROUND: Osteopetrosis is an inherited bone disease associated with high risk of osteoarthritis and fracture non-union, which can lead to total hip arthroplasty (THA). Bone quality and morphology are altered in these patients, and there are limited data on results of THA in these patients. The goals of this study were to describe implant survivorship, clinical outcomes, radiographic results, and complications in patients with osteopetrosis undergoing primary THA. METHODS: We identified 7 patients (9 hips) with osteopetrosis who underwent primary THA between 1970 and 2017 utilizing our total joint registry. The mean age at index THA was 48 years and included two males and five females. The mean follow-up was 8 years. RESULTS: The 10-year survivorship free from any revision or implant removal was 89%, with 1 revision and 1 resection arthroplasty secondary to periprosthetic femoral fractures. The 10-year survivorship free from any reoperation was 42%, with 4 additional reoperations (2 ORIFs for periprosthetic femoral fractures, 1 sciatic nerve palsy lysis of adhesions, 1 hematoma evacuation). Harris hip scores significantly increased at 5 years (P = .04). Five hips had an intraoperative acetabular fracture, and 1 had an intraoperative femur fracture. All postoperative femoral fractures occurred in patients with intramedullary diameter less than 5 mm at a level 10 cm distal to the lesser trochanter. CONCLUSION: Primary THA in patients with osteopetrosis is associated with good 10-year implant survivorship (89%), but a very high reoperation (58%) and periprosthetic femoral fracture rate (44%). Femoral fractures appear associated with smaller intramedullary diameters.

Anterior cervical arthrodesis for chronic hangman's fracture in a patient with osteopetrosis: a case report.

INTRODUCTION: Osteopetrosis is a clinical syndrome characterized by the failure of osteoclasts to resorb bone. Affected patients usually suffer from repetitive fractures due to this pathological state. Surgical treatment of these fractures is often complicated by the difficulty of working with the extremely hard and brittle bones. The purpose of this study was to report a case of chronic hangman's fracture in a patient with osteopetrosis who underwent surgery for cervical anterior interbody fusion. MATERIALS AND METHODS: A 76-year-old woman visited our institute 1 month after injury. Radiographs revealed a type II hangman's fracture with severe translation according to the Levine-Edwards classification. We performed anterior spinal arthrodesis from C2 to C3. RESULTS: We obtained successful anterior C2-C3 arthrodesis without major complications, but encountered some surgical difficulties in treatment due to hard and brittle bones. CONCLUSIONS: Anterior cervical arthrodesis can be considered an effective treatment for chronic unstable hangman's fracture in patients with osteopetrosis. However, great care must be taken when performing surgery and continued follow-up is warranted.

Novel mutations of TCIRG1 cause a malignant and mild phenotype of autosomal recessive osteopetrosis (ARO) in four Chinese families.

Human autosomal recessive osteopetrosis (ARO), also known as infantile malignant osteopetrosis, is a rare genetic bone disorder that often causes death. Mutations in T-cell immune regulator 1 (TCIRG1) are a frequent cause of human ARO. Six additional genes (TNFSF11, TNFRSF11A, CLCN7, OSTM1, SNX10, PLEKHM1) were also found to be associated with human ARO. In order to expand the mutation spectrum and clinical diversity for a better understanding of the ARO phenotype and to further investigate the clinical characteristics of benign subjects with ARO, we here report five individuals with ARO from four unrelated Chinese families. X-ray examination was conducted and bone turnover markers were assayed. The gene of T-cell immune regulator 1 (TCIRG1) was screened and analyzed. Monocyte-induced osteoclasts were prepared and their resorption ability was studied in vitro. We identified five novel mutations (c.66delC, c.1020+1_1020+5dup, c.2181C>A, c.2236+6T>G, c.692delA) in these patients. Four patients displayed a malignant phenotype, three of them died, and one who received bone marrow transplantation survived. The remaining one, a 24-year-old male from a consanguineous family, was diagnosed based on radiological findings but presented no neurological or hematological defects. He was homozygous for c.2236+6T>G in intron 18; this mutation influenced the splicing process. An in vitro functional study of this novel splicing defect showed no resorption pits on dentine slices. TCIRG1-dependent osteopetrosis with a mild clinical course was observed for the first time in Chinese population. The present findings add to the wide range of phenotypes of Chinese patients with TCIRG1-dependent ARO and enrich the database of TCIRG1 mutations.

Case update on cranial osteopetrosis: which is the role of the neurosurgeon?

PURPOSE: Osteopetrosis (OP) is a rare skeletal disease, which can affect the skull base and calvaria. A multidisciplinary approach is mandatory and patient may need neurosurgical care. Few observations have been published, and optimal management of OP is not established yet. METHOD: We report a case of an infant with OP diagnosed at 5 months, who presented signs of intracranial hypertension associated with unilateral blindness. Bone marrow allograft was performed at 6 months of age. At neurosurgical first examination at 11 months, the child was hypotonic, with severe amblyopia; features of bicoronal synostosis were appreciated, with tense anterior fontanel bulging indicating synostotic oxycephaly. Head circumference had decreased from +3 SD to +1SD. Cerebral CT scan showed reduction of intracranial volume, inward thickening of the calvaria, bilateral stenosis of optic canal, ventricular dilatation, enlarged arachnoid spaces, and tonsillar herniation. We performed cranial vault expansion with frontal advancement and bi parietal decompression, thinning of the inner table, unroofing of the left orbit and optic canal in order to obtain optic nerve decompression. RESULTS: Postoperative course was uneventful, and the patient was discharged on day 8. Vision was unchanged but rapid improvement of axial tonus was noted. The CT scan showed satisfactory calvarial expansion with regression of tonsillar herniation. CONCLUSIONS: Neurosurgical evaluation and care are necessary in the context of a multidisciplinary approach to the patient affected by osteopetrosis. Cranial vault remodeling and expansion should be considered in patients with sign of intracranial hypertension. Timing of optic canal decompression is to be defined.

Case report: A 10 years follow-up of periprosthetic femoral fracture after total hip arthroplasty in osteopetrosis.

Osteopetrosis is an inherited disorder characterized by increased bone density and brittle bone quality. Degenerative changes often occur after the age of 40 in patients with osteopetrosis. Operative intervention is the primary treatment option if the clinical manifestation of secondary osteoarthritis is severe. A 44-year-old male suffering autosomal dominant osteopetrosis and progressive unilateral hip osteoarthritis required a total hip arthroplasty. However, there were several technical challenges associated with this procedure including creating a femoral medullary canal and developing a Vancouver type B2 periprosthetic femoral fracture postoperatively. To afford some experience for the management of similar cases, we here present our technical solutions to these problems.

Ultrastructural Analyses of Alveolar Bone in a Patient With Osteomyelitis Secondary to Osteopetrosis: A Review of the Literature.

Osteopetrosis is a generic term for generalized sclerotic conditions caused by rare genetic disorders. Decreased osteoclastic activities disturb bone remodeling, resulting in greater mineral density and greater compressive strength; therefore, bone fracture is a major physical symptom of osteopetrosis. Osteomyelitis of the maxilla or mandible is a common and well-documented complication of osteopetrosis. Local infection, such as odontogenic infection, is more likely to lead to osteomyelitis, and treatment strategies can be challenging. However, detailed ultrastructural analyses of bone from patients with osteopetrosis and odontogenic infection are limited. This report describes a case of osteomyelitis of the maxilla and mandible secondary to osteopetrosis in an adult patient and presents ultrastructural data of alveolar bone tissue analyzed by contact microradiography, electron probe microanalysis, and x-ray diffraction. Cases of osteomyelitis of the jaw secondary to osteopetrosis also are reviewed.

Clinical Characteristics and Treatment of Osteopetrosis Complicated by Osteomyelitis of the Mandible.

Osteopetrosis represents a heterogeneous group of rare, hereditary bone disorders with variable clinical features, and an increase in bone density. Osteomyelitis of the jaws is a significant complication of osteopetrosis. In this article, a reported patient with osteopetrosis complicated by osteomyelitis of the mandible was examined. The patient was treated with intravenous antibiotic therapy, debridement of necrotic bone and hyperbaric oxygen therapy; in addition, the authors attempted to implant the calcium sulfate and vancomycin to reconstruct the bone defect. The patient demonstrated satisfactory healing, and no recurrence of osteomyelitis was observed during the 6-month follow-up period. The treatment of osteopetrosis complicated by osteomyelitis of the mandible is difficult. The treatment of osteopetrosis complicated by osteomyelitis is controversial. The authors recommend the following sequential treatment of osteopetrosis complicated by osteomyelitis of the mandible: systemic antibiotic therapy and hyperbaric oxygen therapy before and after surgery; debridement of the necrotic bone; sufficient periosteal coverage and adequate soft tissue to cover the wound; implantation with calcium sulfate and vancomycin to reconstruct the bone defect as much as possible, which may be helpful in treating the disease.

Maxillomandibular osteomyelitis associated with osteopetrosis.

Osteopetrosis is a heterogeneous disorder characterized by abnormal bone remodeling and increased bone density primarily due to defective osteoclast resorption. The diagnosis is based on a history of numerous fractures and radiological findings indicative of osteosclerosis, usually sufficient for a definitive diagnosis. We present a quite rare case of osteopetrosis complicated by recurrent episodes of maxillomandibular osteomyelitis associated with cutaneous fistulization and purulent nasal discharge. We used intravenous antibiotic therapy and necrotic bone debridement that prevented the appearance of acute infections over a 3-year follow-up, but the complete healing of the case was not achieved.

Prosthetic aspects in adult osteopetrosis.

Osteopetrosis (OP) is a rare condition characterized by skeletal sclerosis caused by dysfunctional osteoclasts. Though many reports have described severe infantile-malignant autosomal recessive OP, few have described the prosthetic management of adult OP. This report discusses the prosthetic treatment of adult OP. Although prosthodontists should try to reconstruct occlusal function as much as possible, a conservative prosthodontic approach may be a reasonable and recommended treatment option for minimizing the risk of further osteomyelitis and osteonecrosis.

Conversion Total Hip Arthroplasty in Patients With Osteopetrosis: Insights From Two Unique Cases.

CASE: Two patients with osteopetrosis underwent conversion total hip arthroplasty (THA) after failure of internal fixation due to hip fractures. We experienced challenges, including difficulty of hardware removal, remaining of previous broken screws in the canal, difficulty in finding the femoral canal, and an intraoperative acetabulum fracture. Despite complications, both patients achieved satisfactory functional outcome after surgery at the latest follow-up. CONCLUSION: Our cases showed that previous hip fracture and failed internal fixation make conversion THA more complex and unpredictable in patients with osteopetrosis. This in turn underscores the critical need for advanced preoperative planning, intraoperative flexibility, and meticulous postoperative care.

Challenges of Hip and Knee Arthroplasty in Patients With Osteopetrosis.

Osteopetrosis is a rare metabolic bone disease, characterized by dysfunction of osteoclasts, resulting in increased bone density and brittleness leading to pathological fractures and bone deformities. Hip and knee osteoarthritis (OA) are common long-term complications in patients with osteopetrosis. Joint arthroplasty surgery remains an effective and recommended treatment for these patients with an end-stage OA because it provides favorable outcomes. However, in osteopetrosis, joint arthroplasty surgery carries an increased risk of complications, and specific preoperative and perioperative considerations are required to deal with the technical challenges related to the disease. The aim of this article was to review some of the key aspects of osteopetrosis, provide technical recommendations, and answer clinically relevant questions related to hip and knee arthroplasty surgery.

Successful cord blood transplantation in a patient with malignant infantile osteopetrosis and hemophilia.

MIOP is a congenital disorder of osteoclast differentiation or dysfunction. Inadequate bone resorption by osteoclasts results in a spectrum of complications including hypocalcemia, osteosclerosis, marrow failure, extramedullary hematopoiesis, hydrocephalus, visual deficits, and eventual mortality. Early diagnosis and timely HCT is a recommended treatment approach for select patients prior to the development of end-organ damage. A comorbid bleeding disorder presents a unique challenge in the setting of MIOP and cord blood HCT given the additional risk factors for bleeding including delayed engraftment, a high risk of developing sinusoidal obstruction syndrome, and potential need for emergent invasive procedures. To our knowledge, this is the first report of a patient with an autosomal recessive form of MIOP who successfully underwent a cord blood HCT complicated by the presence of mild hemophilia A and HCT-related complications including delayed engraftment, sinusoidal obstruction syndrome, and need for multiple invasive procedures (e.g., ventriculostomy, tracheostomy) without clinically significant bleeding. Given the underlying diagnosis of MIOP and need for HCT, the challenge of mitigating the significant risk of bleeding in a patient with a comorbid bleeding disorder is discussed.

Surgical treatment of an osteopetrotic patient with postoperative fractures: lessons from siblings with osteopetrosis.

Osteopetrosis is a rare, inherited disease characterized by dense and brittle bones, and it is associated with an increased risk of femoral fractures. However, the surgical treatment of the fracture patients with osteopetrosis is a subject of controversy, because it is difficult to compare the treatment effects between surgical treatment and conservative treatment in part due to the rarity of siblings with osteopetrosis. In fact, the genetic background and the environmental factors, such as living conditions and daily work, may influence the prognosis of the fracture patients with osteopetrosis. Here we describe siblings with osteopetrosis, a 23-year-old female patient and her older brother, both of whom had suffered from bilateral femoral fractures at their childhood. They do not have other brothers or sisters, and their parents are healthy. The younger sister had undergone surgical treatment for femoral fractures at the age of 8 years and recovered very well. In contrast, her brother had received the conservative treatment for femoral fractures at the age of 6 years, and thereafter he is badly disabled due to the malunion of the fractured femurs. Apparently, the surgical treatment is superior to the conservative treatment for the fracture patient with osteopetrosis. Unfortunately, fifteen years later, the sister fractured again at both femurs and underwent another operation. She recovered quickly from the second operation, indicating that second operation should be considered in osteopetrosis patients with postoperative fractures. The present report provides valuable information for the choice of treatment of femoral fractures associated with osteopetrosis.

[Visual function of seven children with malignant osteopetrosis after hematopoietic stem cell transplantation].

OBJECTIVE: To detect long-term ocular alteration of children with malignant osteopetrosis after hematopoietic stem cell transplantation. METHODS: Children diagnosed as osteopetrosis from 5 months to 31 months underwent hematopoietic stem cell transplantation. Computed tomography of optic canal, FVEP, ERG and fundus examination were applied to assess the visual function. RESULTS: Bone marrow transplantation was successful. Peripheral blood test, splenohepatomegalia and osteosclerosis improved gradually. The mean optic canal diameters of right eyes before transplantation was (1.7 ± 0.4)mm. The mean optic canal diameters of right eyes was (3.2 ± 0.7)mm after transplantation. The mean optic canal diameters of left eyes before transplantation was (1.9 ± 0.5)mm . The mean optic canal diameters of left eyes was (3.1 ± 0.8)mm after transplantation. The difference between above two groups was statistically significant(t = -5.204, -4.211;P < 0.05). P2 latency period of FVEP prolonged in 7 cases before transplantation. Mean P2 latency period of FVEP decreased 21.13 ms in 5 cases after transplantation. Mean P2 latency period of FVEP prolonged 22.25 ms in 2 cases after transplantation. Under light adaptation and dark adaptation, ERG amplitude depressed obviously in 2 cases. Two cases with optic nerve atrophy did not change after transplantation. CONCLUSIONS: Hematopoietic stem cell transplantation is an effective way to deal with malignant osteopetrosis. Successful transplantation has been shown to arrest visual deterioration in some cases.