Multiple Cartilaginous Exostoses Research Articles

Multiple cartilaginous exostoses of rib in dog: a case report

Multiple cartilaginous exostoses of rib in dog: a case report

Lumbar Myelopathy Caused by Multiple Cartilaginous Exostoses in a Dog

A 6-months-old male mixed-breed dog was admitted to the veterinary hospital with lameness in the right pelvic limb, proprioceptive ataxia, and suspected spinal cord injury in the lumbosacral segment. Upon palpation, firm nodules were noted on the bony surface of the thoracic and pelvic limbs, ribs, vertebrae, and tail. The radiographic study showed nodules of low radiopacity with well-defined limits and smooth contours, one of which was overlapping the fifth lumbar vertebra. Given the clinical presentation indicative of spinal cord injury, the animal was subjected to hemilaminectomy for nodular resection. Histopathological examination of the biopsy enabled the diagnosis of osteochondroma. The clinical follow up after surgery showed improvement in walking, despite persistent monoparesis in the right pelvic limb. The radiographic study in association with clinical and histopathological exams allowed the diagnosis and monitoring of the lesions.

Multiple Cartilaginous Exostoses Causing Severe Cervical Myelopathy in a Puppy Dog

AbstractThis study aimed to report a case of multiple cartilaginous exostoses (MCE) causing severe cervical myelopathy in a puppy dog. An 80-day-old Dachshund cross weighing 2.2 kg presented with progressive development of non-ambulatory tetraparesis, proprioceptive ataxia in all four limbs, and cervical hyperesthesia. Multiple calcified masses in the cervical spine at the levels of C1–C2 and C4–C7, with several points of spinal cord compression, were identified. Ventral atlantoaxial fusion was performed. Four days later, four masses were surgically removed by dorsal laminectomy of C1–C2 and C4–C7, and a right facetectomy between C4 and C5 was performed. Multiple cartilaginous exostoses were confirmed by histopathological examination. Thirty-six months after surgery, the patient showed no recurrence of neurological signs. Ventral atlantoaxial fusion, and surgical removal of MCE masses followed by decompression was effective on alleviating clinical sings in the short and medium term.

Cytological and Histopathological Correlation of Feline Giant Cell-Rich Osteosarcoma

Background: Primary bone tumours are uncommon and poorly reported in cats but osteosarcoma (OSA) is the most frequent, mostly in elderly animals. Giant cell-rich OSA is considered rare in the literature representing 3% of all OSA in humans. The mitotic index seems to have a significant effect on the survival time of cats affected by this neoplasm as well as the tumour histopathological grade. The objective of this study was to report the cytological and histopathological findings of a giant cell rich OSA in a 4-year old cat with persistent feline leukemia virus (FeLV) antigenaemia.Case: A 4-year-old male neutered cat was referred with a history of persistent FeLV viraemia and pelvic limb lameness with a firm swelling. Previous radiographs of the affected limb revealed bone lysis in the third and fourth metatarsals and increased soft tissue radiopacity in the tarsal region. The referral veterinary assumed it to be osteomyelitis and initiated clinical treatment with antibiotic and anti-inflammatory. The cat was referred after there was no response to medical treatment. The cat was presented with a 5cm diameter ulcerated mass, with putrid odor in the pelvic limb. Complementary exams were performed, and abnormalities were found, including increased urea, creatinine, calcium and potassium, and decreased sodium and phosphorus. A new radiograph showed exuberant bone proliferation, with increased radiopacity involving tarsal, metatarsal, distal third of tarsal I and II, and distal diaphysis of metatarsal V, without compromising the metaphyseal region of distal diaphysis of metatarsal IV. Chest radiographs and abdominal ultrasound were unremarkable. Fine-needle aspiration was performed for cytological analysis, which reavealed a moderate amount of pleomorphic mesenchymal cells with moderate adhesion, cytoplasm with a format ranging from fusiform to stellate, pronounced anisocytosis and cellular pleomorphism, and elevated nucleus:cytoplasm ratio. Nucleus was oval and presented loose chromatin, single to double large and evident nucleolus, frequent karyomegaly, along with marked anisocariosis and nuclear pleomorphism. Multinucleated giant cells were and there was a single mitotic figure in 12 high power fields (0.196 mm2 FN20/400x). Therefore, it was suggestive of malignant mesenchymal neoplasia with possibility of OSA, fibrosarcoma oe undifferentiated sarcoma. Limb amputation with femoral disarticulation was performed uneventfully. The material was conserved in 10% formalin, submitted to macroscopic and microscopic evaluation, which showed a large number of fusiform and stellate cells, with indistinct edges, scarce eosinophilic cytoplasm, high nucleus:cytoplasm ratio and oval nucleus, presenting moderate to marked anisocariosis, loose chromatin, with unique and evident nucleoli, besides of bone trabeculae. Nuclear pleomorphism was moderate and there was four mitotic figures in three random high-power fields (400x). It was observed areas of vascular ectasia, and neoplastic embolization in lymphatic and blood vessels. Among the cells, collagenous stroma was predominant but in some areas there was an eosinophilic amorphous material with the possibility of osteoid matrix or collagen. There was also a large numbers of multinucleated giant cells. The histopathological result was compatible with a grade III giant cell rich OSA.Discussion: Although bone tumours are uncommon in cats, OSA is the most frequent, affecting maingly middle-aged to elderly cats, with a mean age of 10 years, which is different from the present report in a 4-year old cat, with FeLV persistent viraemia. Retroviral status may have influenced the development of the disease at na early onset. FeLV induces uncontrolled cell proliferation through insertional mutagenesis (usually near myc) inducing malignant neoplasias, mainly lymphoma, but also multiple cartilaginous exostosis, which, along with osteomyelitis and bone cyst were included in this patient´s list of differential diagnoses. Despite the macroscopic and radiographical andagressiveness there was no metastasis identified through chest radiographs or abdominal ultrasound, and feline OSA is associated with a lower metastatic rate, if compared to canine OSA. Cytological analysis was compatible with malignant mesenchymal neoplasia, being suggestive of giant cell rich OSA. There is no cytological classification for OSA, however cytological findings of malignancy may be correlated with the patient's clinical course. Cytological features were in agreement with the histopathological findings, compatible with a grade III giant cell rich OSA. Therefore, it is concluded that the characteristics of malignancy presented by cytology were sufficient for the recommendation of amputation of the affected limb, once there was no imaging sign of metastases in the chest or abdomen.

Случай множественной экзостозной хондродисплазии в якутской семье, обусловленной редкой мутацией в гене EXT2

Введение. Множественная экзостозная хондродисплазия (МЭХД) - наследственное аутосомно-доминантное заболевание скелета, которое характеризуется образованием множественных хрящевых экзостозов в зонах роста костей. Консультирование семей с МЭХД является сложной задачей для врача-генетика. В статье приведены клинические, молекулярно-генетические данные обследования большой якутской семьи с аутосомно-доминантной наследственной МЭХД, причиной которой является редкая мутация в гене EXT2. Цель: проведение клинико-генеалогического, молекулярно-генетического обследования больных с клиническим диагнозом МЭХД. Методы. В исследование включены 4 поколения одной якутской семьи (11 больных и здоровых членов). Секвенирование экзома одного члена семьи (ДНК пробанда) проводилось на секвенаторе MiSeq Illumina с использованием панели, включающей 4800 генов. Патогенность выявленной мутации подтверждалась in silico, а также секвенированием по Сэнгеру с использованием ДНК пробанда, его родителей. Данный метод также был использован для выявления мутации у остальных членов семьи. Результаты. В результате молекулярно-генетического исследования у 7 членов семьи с клиническим диагнозом МЭХД была выявлена редкая нонсенс-мутация c.751С>T в экзоне 5 гена EXT2 в гетерозиготном состоянии. Данная мутация отсутствовала у 4 здоровых членов этой семьи, а также в 10 образцах из контрольной группы. Оценка патогенности выявленной мутации показала, что данная мутация является причиной возникновения МЭХД в якутской семье. Заключение. Ранняя медицинская помощь пациентам с диагнозом МЭХД может дать возможность оказания медицинской помощи пациентам специалистами разного профиля, а также сосредоточить внимание врачей на ортопедических проблемах в раннем возрасте. Introduction. Multiple osteohondromas (MO) is an autosomal dominant inherited skeletal disease characterized by the formation of multiple cartilaginous exostoses in the areas of growth in a long bones. Difficult issues arise for the genetic counseling of families with MO. We presents the clinical and molecular genetic analysis of four-generation Yakut family with an autosomal dominant inherited MO, caused by a rare mutation in the EXT2 gene. Aim: сonducting a clinical, genealogical, molecular genetic study of patients with a clinical diagnosis MO. Methods. Targeted panel sequencing performed for the 4800 known candidate genes using Trusight One Sequencing Panel (Illumina Inc., USA) on one sample (DNA of proband). Sanger sequencing was performed for validation of candidate disease causing mutation in DNA from a proband and family members. Results. A rare EXT2 nonsense mutation (c.751C> T, p.Gln251*) was revealed by targeted exome sequencing and validated by Sanger sequencing in the 7 MO-affected members of this family. The variant was interpreted as pathogenic based on an in silico analysis. This mutation was absent in 4 healthy members of this family and in 10 controls. Conclusions. This is the first study of EXT2 gene mutation in a Russian patients from Yakut family with MO. Timely health care of patients with diagnosis of MO can contribute to establishment coordinated multispecialty management of the patient focusing on the orthopedic problems issues through childhood.

Multiple cartilaginous exostoses in a Swiss Mountain dog causing thoracolumbar compressive myelopathy

BackgroundMultiple cartilaginous exostoses are a rare, benign, proliferative condition of cartilage and bone. They can be asymptomatic, or they may cause pain, lameness, paresis and even paralysis, depending on their location and size. In cases of spinal cord or nerve root compression, surgery is the treatment of choice. Therefore, an advanced imaging diagnostic work-up is indicated. Due to the unclear pathophysiology and progression of this condition, it is difficult to predict its prognosis.Case presentationA 9-month-old female Swiss Mountain dog was presented with a history of gait abnormalities, kyphosis and hypersensitivity consistent with a thoracolumbar myelopathy. Multiple calcified masses, most prominent at the Th7–Th9 level and the L2–L3 level, were observed. Magnetic resonance imaging of the thoracolumbar vertebral column revealed severe dorsal spinal cord compressions near the dorsal arch of the Th7–Th9 and L2–L3 vertebrae. Two of these masses were removed surgically. The successful removal of both masses was confirmed by postoperative computed tomography. The histopathological examination of the resected tissue revealed multiple cartilaginous exostoses. The first neurological and magnetic resonance follow up examination carried out 6 months postoperatively showed improvement of the clinical status. At that time, no mass regrowth was observed. The last follow up neurological examination carried out 15 months postoperatively showed gait improvement and resolution of pain.ConclusionThis is the first case report of multiple cartilaginous exostoses with a complete pre- and postoperative evaluation and a 15 month follow-up.

Multiple Cartilaginous Exostoses In A Pediatric Dog

Background: Multiple cartilaginous exostosis (MCE) is a rare neoplastic disease in dogs that is characterized by the presence of osteochondromas in multiple bones. MCE is a disorder of development during growth and maturation, the real etiology of which has yet to be elucidated, but is believed to have a genetic basis. Usually affected animals have a history of a palpable mass on the bone surface, causing anatomical deformities and compression of adjacent structures. Since MCE is a rare neoplastic disease in dogs it may be difficult to recognize in the clinic. The aim of this study was to report a case of MCE in a pediatric dog.Case: A female 4-month-old Rottweiler dog with a history of bone neoformation on the left hind limb, anorexia, weight loss, and difficulty walking received clinical care. The disease had its initial onset 2 months prior. At physical examination, the animal showed paresis of the hind limbs and a bony tumor on the lateral part of the left tibia. A complete blood cell count and serum biochemical profile were obtained. The only abnormality diagnosed was hyperproteinemia due to hyperglobulinemia. Other diagnostic tests were not authorized and the animal was euthanized. At the necropsy, an intrathoracic neoformation was observed from the sixth to the eighth rib on the right antimer. Some tumors were also observed on the fourth lumbar vertebra and between the first and the second sacral vertebra, and a left tibial tumor, which had been observed at physical examination. The sagittal section of the spine revealed the presence of extradural compression of the spinal cord due to vertebral proliferations with compression of the nerve roots. All of the proliferations had macroscopic similarities, being firm, sessile, irregular, and with complete adherence to deep planes. Tumor samples were submitted to histopathological analysis and the tissue morphology was compatible with osteochondroma. Based on the clinical, necroscopical, and histopathological findings, a diagnosis of MCE was established.Discussion: In MCE, animals less than one year of age are the most frequently affected, as was observed in the case reported. Clinical signs in MCE usually result from poor bone and cartilaginous anatomical formations and from compression of adjacent tissue structures. In the described patient, the proliferations located in the vertebrae and tibia and the consequent compression of nerve roots and nerves caused the neurological deficits. Unlike in canines, the etiology of MCE in humans is already well established and it is classified as an autosomal dominant genetic disorder. The diagnosis is usually obtained through the association of clinical examination with radiographic and histopathological findings. However, in the animal studied, since it was not possible to perform radiographs, confirmation was obtained only after performing histopathological examination of the neoformations, which is considered the standard for the diagnosis of MCE. Although it corresponds to a benign neoplastic process affecting dogs during their growth stage, it may significantly decrease the animal’s quality of life. In this situation, the prognosis of MCE is considered to be reserved to bad, and animals are often referred for euthanasia, as occurred in the animal under discussion, due to the progression of neurological dysfunction. Early recognition of MCE in routine pet hospital practice is of fundamental importance in order to properly institute treatment and monitoring.

Hypertension in Potocki-Shaffer syndrome: A case report

Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome caused by heterozygous deletion of 11p11.2p12. Typical features described in patients with PSS include developmental delay, intellectual disability, multiple cartilaginous exostoses, biparietal foramina, craniofacial abnormalities, and genitourinary anomalies. While hypertension has been noted in three patients with PSS, it has not been described in most patients with this syndrome. This report details the evaluation and treatment of a teenager with PSS who presented on several occasions during childhood with elevated blood pressure measurements. The renin level was elevated, likely indicating a secondary cause for the HTN. The patient's BP responded to monotherapy with Angiotensin Converting Enzyme Inhibitor (ACEI).

Excisão cirúrgica de um osteocondroma de raiz nervosa da cauda equina de cão

Background: Spinal neoplasms are classified into extradural, intradural/extramedullary or intramedullary. Intradural/extramedullary tumors include meningiomas and nerve sheath tumors, which arise from meninges or peripheral nerves around the spinal cord. Clinical signs are related to dysfunction of the involved nerve and include pain, nerve root signature and atrophy. Osteochondromas are benign tumors located within the bone, on its surface or in extra-osseous regions, when they are classified as soft tissue osteochondoma. The aim of this study is to describe a case of an osteochondroma in a nervous root of the cauda equina in a dog, whose surgical resection allowed the resolution of the clinical signs.Case: A 12-year-old, male, Labrador Retriever dog, was presented with a 40-day history of progressive, painful, pelvic limb paresis, with no improvement when treated with analgesics and acupuncture. Neurological abnormalities included paraparesis, sometimes worse in the left pelvic limb, that was carried flexed at the level of the stifle, hindlimb atrophy, decreased interdigital reflexes and pain in the lumbar spinal region, mainly over L6 vertebra. Results of blood count and serum biochemical analysis were unremarkable. Computed tomography (CT) of the lumbosacral area was performed and the evaluation of images in transverse and reconstructed dorsal and sagittal planes allowed the visualization of a hyperattenuating and calcified round structure with 8 mm x 6 mm, in the left side of vertebral canal, at the level of caudal epiphysis of L6. Lumbosacral (L7-S1) CT abnormalities, as subchondral sclerosis, mild disc margin bulging, spondylosis deformans and foraminal proliferation were also observed but were considered clinically insignificant. Then, a dorsal L6 laminectomy was performed and after opening of the vertebral canal it was observed the presence of an ovoid mass, in the left side of the medullary cone, measuring approximately 0.9 cm in length, originating from a sacral nerve root. This structure was excised and submitted to histopathological evaluation. The dog improved after surgery without any complications, and neurological functions were gradually recovered. The histopathology of the mass was confirmed as an osteochondroma.Discussion: The history and neurologic examination findings as well the improvement after surgery were compatible with the lesion visualized by TC in L6, rather than the degenerative changes in L7-S1. Regarding the position of the mass, the main differential would be nerve sheath tumor, one of the most common types of primary neoplasia of the peripheral nervous system, however in a CT study in dogs with brachial plexus and nerve roots neoplasms, calcification of the tumor was not observed. Most of benign cartilaginous tumors of soft tissue are chondromas/osteochondromas, and this lesion should not be confused with multiple osteochondroma or multiple cartilaginous exostoses, which have been reported as multifocal, proliferative lesions involving the surface of ribs, vertebrae and pelvis of young dogs. If this lesion is unique, it is called osteochondroma. There are two reports of chondromas into the first lumbar vertebrae of dogs, with adherence to the floor of the vertebral canal and one report of an osteochondroma originated from the left pedicle of T11 in a cat. Radiculopathy and myelopathy caused by osteochondromas inside the spine are rare in humans and description of this tumor arising from nerve roots were not found in the veterinary literature. Probably the origin of the mass was metaplasia of the meninges surrounding the nervous root. In conclusion, neurological examination, CT and surgical exploration allowed the diagnosis and removal of a soft tissue osteochondroma, a rare benign tumor, with good patient recovery.

Novel exostosin-2 mutation identified in a Chinese family with hereditary multiple osteochondroma.

Hereditary multiple osteochondroma (HMO) is an autosomal dominant genetic disorder characterized by multiple outgrowing bony tumors capped by cartilage, generally affecting the metaphyses. The disease is known as hereditary multiple exostoses, familial exostosis, multiple cartilaginous exostoses or hereditary malformation of cartilage. The prevalence of HMO in Europe and the Unites States is ~1:100,000, although it has not been reported in China. The disease is often accompanied by pain, asymmetry and skeletal malformations, including forearm and leg bending deformities, limb length discrepancies, and knee internal and external rotation abnormalities. Mutations to exostosin-1 (EXT1) and EXT2 mutations cause insufficient heparan sulfate biosynthesis, leading to chondrocyte proliferation, abnormal bone growth in neighboring regions, multiple exostoses, and ultimately malignant transformation. The risk of malignant degeneration to osteochondrosarcoma increases with age, despite the low lifetime risk (~1%). The present study selected a clinical feature of typical HMO pedigrees, and examined mutations in family members by Sanger sequencing. Each of the five patients examined had a novel heterozygous nonsense mutation, c.67C>T p.Arg23*. The mutation is located prior to the EXT2 exostosin domains in the amino acid sequence and results in a protein truncation of the 705 C-terminal amino acids. The present study provides molecular genetic evidence for a novel causal mechanism of HMO, and provides the basis for clinical genetic counseling for similar diseases.

Multiple cartilaginous exostosis: Case report

This article reports the care of two dogs from Teckel race, both with a history of limited mobility and loss of proprioception, no changes in hematic tests. The first dog, a female, 4 months old, had to take radiographic presence of radiopaque mass at the distal femoral metaphysis, proximal and distal tibia and the proximal left fibula, and similar structures at the spinous processes of T3, T6 and T7 and the third right rib, protruding into the chest cavity. The second dog, a male 6 months old, had nodular bone mass in the ischium and ilium, and proximal metaphysis of tibiae and distal right tibia, as well as similar changes in the ribs protruding both to the surface external and internal chest. Therefore, after the X-ray analysis was diagnosed multiple cartilaginous exostosis (ECM), a disease characterized by bone projections covered with cartilage. It was adopted as a therapeutic measure the use of tramadol and the monitoring of disease progression.

多発性外骨腫症の下肢変形に対するGuided Growth Systemの治療経験

多発性外骨腫症の下肢変形に対するGuided Growth Systemの治療経験

Osteochondroma of the Proximal Fibula-Revisited

It was interesting to read the case report by Kumar et al., [1]. “Osteochondroma arising from the proximal fibula: a rare presentation”, where the authors mentioned about a case of a giant osteochondroma arising from the proximal fibula in an 18-year-old male without the complications of distal neurovascular deficit or a sarcomatous change. We congratulate the authors for such a nice presentation of this common tumour with various case scenarios. The authors mentioned in the title ‘Osteochondroma arising from the proximal fibula: a rare presentation’ which in fact contradicts the statement written in the discussion ‘the most common tumours found in the proximal fibula are osteochondromas, giant cell tumours, osteosarcomas and ewing’s sarcomas’ [1]. Literature gives identical statistics and concludes that the proximal fibula is a common site for symptomatic Osteochondroma [2]. Involvement of the tibia in a case of solitary osteochondroma of proximal fibula is rare and coalescence of kissing osteochondromata (facing osteochondromas of both tibia and fibula may show an interlocking growth at the abutting parts) in patients with multiple cartilaginous exostoses (MCE) may result in tibiofibular synostosis. Hence, the tibial involvement as mentioned by the authors could actually be the scalloping of the proximal tibia due to erosion on the contagious surface adjacent to the giant proximal fibular lesion. Though there were no symptoms of neurovascular involvement in the case reported by the authors, knowledge of the possible complications from the neurovascular involvement as mentioned by the authors should be born in mind especially in cases of a giant tumours at such a notorious anatomical site [1,3,4]. Preoperative nerve conduction studies and the angiography or colour doppler ultrasonography would be invaluable in planning definitive treatment. The authors did an en block resection of the lesion leaving a very small portion of the head of fibula where the lateral collateral ligament (LCL) was attached. In the one year follow-up they did not mention about the status of the knee joint laxity which could have judged the requirement of a LCL repair or reconstruction. Type 1 en block resection of proximal fibula is indicated for aggressive or epiphyseally located tumours where LCL repair and reconstruction is necessary to address the knee instability. Abdel Matthew et al., [5], in their study did en block resection of tumours at proximal fibula followed by LCL and biceps femoris repair or reconstruction. They found no functional knee instability. Last but not the least, further follow-up of the case is required keeping in mind the possibility of recurrence or the malignant transformation. The purpose of this letter is to highlight the key points regarding such an important entity. In the end, we wish to thank the authors for presenting such a difficult to treat case to the readers.

Long‐term follow‐up of four patients with langer–giedion syndrome: Clinical course and complications

Long-term observations of individuals with the so-called Langer-Giedion (LGS) or tricho-rhino-phalangeal type II (TRPS2) are scarce. We report here a on follow-up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone-shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11-q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self-esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non-mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos.

IMAGING DIAGNOSIS: MULTIPLE CARTILAGINOUS EXOSTOSES AND CALCINOSIS CIRCUMSCRIPTA OCCURRING SIMULTANEOUSLY IN THE CERVICAL SPINE OF A DOG

An 8-month-old female Saint Bernard dog was presented with gait abnormalities consistent with a left-lateralizing cervical myelopathy. Imaging revealed a large, irregular soft tissue and mineral mass at the level of C1 and C2. The lesion was successfully excised, and histopathology was performed, revealing evidence of both multiple cartilaginous exostoses and calcinosis circumscripta. To the authors' knowledge, this is the first report comparing features using magnetic resonance imaging, computed tomography, and radiography. Additionally, multiple cartilaginous exostoses have not previously been reported to occur in combination with calcinosis circumscripta.

A systematic review of genetic skeletal disorders reported in Chinese biomedical journals between 1978 and 2012

Little information is available on the prevalence, geographic distribution and mutation spectrum of genetic skeletal disorders (GSDs) in China. This study systematically reviewed GSDs as defined in “Nosology and Classification of genetic skeletal disorders (2010 version)” using Chinese biomedical literature published over the past 34 years from 1978 to 2012. In total, 16,099 GSDs have been reported. The most frequently reported disorders were Marfan syndrome, osteogenesis imperfecta, fibrous dysplasia, mucopolysaccharidosis, multiple cartilaginous exostoses, neurofibromatosis type 1 (NF1), osteopetrosis, achondroplasia, enchondromatosis (Ollier), and osteopoikilosis, accounting for 76.5% (12,312 cases) of the total cases. Five groups (group 8, 12, 14, 18, 21) defined by “Nosology and Classification of genetic skeletal disorders” have not been reported in the Chinese biomedical literature. Gene mutation testing was performed in only a minor portion of the 16,099 cases of GSDs (187 cases, 1.16%). In total, 37 genes for 41 different GSDs were reported in Chinese biomedical literature, including 43 novel mutations. This review revealed a significant imbalance in rare disease identification in terms of geographic regions and hospital levels, suggesting the need to create a national multi-level network to meet the specific challenge of care for rare diseases in China.

Craniomaxillofacial Features in Hereditary Multiple Exostosis

Hereditary multiple exostosis is the most common form of bone dysplasia. This entity is also known as diaphyseal aclasis, hereditary deforming chondrodysplasia, multiple hereditary exostoses, multiple osteochondromatosis, multiple cartilaginous exostosis, dyschondroplasia, and Ehrenfried disease. It is an inherited autosomal dominant disease with predominance in males and a benign condition characterized by the presence of multiple exostosis or osteochondromas arising from long and flat bones.Osteochondroma is the most common benign tumor in persons between 10 and 30 years of age. It accounts for 20% to 50% of all benign tumors and 10% to 15% of all bone tumors. It is more commonly located at the level of the metaphysis of long bones. However, osteochondroma is rare at the level of the facial bones and skull base. It has been reported in the maxillary sinus and in different parts of the mandible, such as the condyle, ramus, body, and symphyseal region. It is very uncommon in the coronoid process and occipital bone.Jacob disease, or osteochondroma of the mandibular coronoid process, is a benign skeletal tumor that is rare in the oral and maxillofacial skeleton. A review of the literature revealed only 41 histologically proven cases of 52 reported cases. To the best of the authors' knowledge this is the first clinical report of bilateral coronoid osteochondroma and associated occipital exostosis in a patient with hereditary multiple exostosis.

Modified Ilizarov technique for the treatment of forearm deformities in multiple cartilaginous exostoses: case series and literature review

The aim of this study is to evaluate the results of gradual ulnar correction and lengthening using the modified Ilizarov technique for the treatment of forearm deformities in patients with multiple cartilaginous exostoses. We retrospectively reviewed 23 forearms in 16 patients. Three different types of operative procedures were performed: (1) corrective osteotomy and gradual lengthening of the ulna, (2) corrective osteotomy of the radius, and (3) excision of exostoses. We evaluated the radiographs; range of motion of the wrist, forearm, and elbow; and functional status using a questionnaire before and after operation. During the clinical interview, post-operative functional status was significantly improved than pre-operative functional status, 12 patients stated that they had no difficulty in performing daily activities, 11 patients stated that they had no pain, and 11 patients stated that the post-operative appearance of the operated forearm was satisfactory. At time of final follow-up, the mean range of motion of the wrist in ulnar/radial deviation, forearm pronation/supination was significantly improved. Also, the radiographic parameters including radial articular angle, carpal slip, radial bowing, and ulnar variance were significantly improved at time of final follow-up. In conclusion, we achieved successful clinical and radiological outcomes in our patients with forearm deformities after treatment with the modified Ilizarov method. However, there could be a recurrence of ulnar shortening and deformity during growth periods in skeletally immature patients.

Reconstruction of Forearm Deformity by Distraction Osteogenesis in Children With Relative Shortening of the Ulna Due to Multiple Cartilaginous Exostosis

In patients with multiple cartilaginous exostosis, distal ulnar osteochondromas frequently cause forearm deformities, with relative ulnar shortening, wrist joint deviation, and varus bowing. Progressive deformation often leads to pain, functional impairment, and cosmetic problems. Surgical ulnar lengthening is necessary to restore the carpal balance. The results of fixator-controlled ulnar lengthening were investigated in this study, using appropriate clinical and radiologic parameters and focusing on medium-term functional and structural outcomes. Twelve children (3 boys, 9 girls; mean age 9.8 y) with multiple cartilaginous exostosis-induced ulnar shortening treated with fixator-controlled ulnar callotasis were evaluated retrospectively based on clinical and radiographic examinations preoperatively, after fixator removal, and at a follow-up investigation. Subjective symptoms and objective joint function were assessed clinically, whereas the extent of ulnar shortening, radial articular angle, carpal slip, and radial head dislocation were determined radiographically. The average follow-up period was 24.6 months. The mean ulnar shortening and radial articular angle improved significantly, from 14.3 mm or 38.7 degrees preoperatively to 1.7 mm or 25.6 degrees after fixator removal and showed a slight but significant increase to 5.2 mm or 30.1 degrees at the follow-up. Carpal slip and radial head dislocation remained unchanged. With the exception of radial abduction, no notable functional advancement was observed. One unintended ulnar overlengthening with a subsequent ulnocarpal impaction syndrome, one premature callus consolidation, and two fixator dislocations were noted. In agreement with literature reports, carpal balance can be restored over the medium term. However, mild recurrences of ulnar shortening and radial malformation were observed during further development. To prevent deformity progression in immature patients, surgery should be carried out early. The optimal timing of surgery needs to be calculated precisely to take advantage of the high remodeling potential and an acceptable degree of recurrent deformity. Ulnar lengthening is necessary, but overcorrection is inadvisable due to possible ulnocarpal impaction syndrome. As significant remodeling effects on the radius were observed, simultaneous radial correction procedures are not recommended a priori.

Single-stage treatment of complete dislocation of radial head and forearm deformity using distraction osteogenesis in paediatric patients having multiple cartilaginous exostosis

We are reporting the results of single-stage treatment for patients with forearm deformity and radial head luxation due to hereditary multiple exostosis using distraction osteogenesis. Six patients with a mean age of 12 years were treated. Morphological evaluation was made according to Masada (3 of the cases were 2a and 3; 2b). Angular deformities of forearm and wrist were evaluated as described by Fogel (distal radial joint angle was 27°, ulnar variance was 12.8 mm and carpal slip was 71.3%). Mean forearm pronation was 48.4° whilst mean supination was 19.2°. Mean elbow range of motion was 26.6°-103.4° and the mean DASH score was 75. Common surgical procedures were deformity correction, ulnar lengthening and gradual radial head reduction using external fixators. Mean follow-up period was 4.2 years and mean external fixation time was 6 months. Mean amount of ulnar lengthening was 2.9 cm and the distraction index was 14.9 cm/day. Mean radial articular angle was 14.3°, ulnar variance 2.3 mm, carpal slip 55%, forearm pronation 65.9° and supination was 55°. Mean elbow range of motion was 15.8°-119.2°. In the last follow-up, the mean value of DASH score was 8.1. Major and minor complications were seen during the follow ups. Single-stage deformity correction, ulnar lengthening and radial head reduction technique that we have used provide satisfactory functional and cosmetic results. Early surgical correction may lead to even better results.