X-Ray

Bubbly lytic lesion / Ground glass

Imaging tests. Computerized tomography or magnetic resonance imaging scans may be used to determine how extensively your bones are affected.

Bone scan. This test uses radioactive tracers, which are injected into your bloodstream. The damaged parts of your bones take up more of the tracers, which show up more brightly on the scan.

Biopsy. This test uses a hollow needle to remove a small piece of the affected bone for laboratory analysis.

Osteofibrous dysplasia is treated with marginal resection with or without bone grafting, depending on the size of the lesion and the extent of bony involvement. However, due to the high rate of recurrence in skeletally immature individuals, this procedure is usually postponed until skeletal maturity.

A combination of medical tests are used to diagnosis kniest dysplasia. These tests can include:

- Computer Tomography Scan(CT scan) - This test uses multiple images taken at different angles to produce a cross-sectional image of the body.

- Magnetic Resonance Imaging (MRI) - This technique proves detailed images of the body by using magnetic fields and radio waves.

- EOS Imaging - EOS imaging provides information on how musculoskeletal system interacts with the joints. The 3D image is scanned while the patient is standing and allows the physician to view the natural, weight-bearing posture.

- X-rays - X-ray images will allow the physician to have a closer look on whether or not the bones are growing abnormally.

The images taken will help to identify any bone anomalies. Two key features to look for in a patient with kniest dysplasia is the presence of dumb-bell shaped femur bones and coronal clefts in the vertebrae. Other features to look for include:

- Platyspondyly (flat vertebral bodies)

- Kyphoscoliosis (abnormal rounding of the back and lateral curvature of the spine)

- Abnormal growth of epiphyses, metaphyses, and diaphysis

- Short tubular bones

- Narrowed joint spaces

Genetic Testing - A genetic sample may be taken in order to closely look at the patient's DNA. Finding an error in the COL2A1 gene will help identify the condition as a type II chondroldysplasia.

Surgery is curative despite possible local relapses. Wide resection of the tumor and resection arthrodesis with an intramedullary nail, vertebrectomy and femoral head allograft replacement of the vertebral body, resection of the iliac wing and hip joint disarticulation have been among the performed procedures.

The close resemblance of FCMB to fibrocartilaginous dysplasia has suggested to some scholars that they might be closely related entities, although the latter features woven bone trabeculae without osteoblastic rimming, which is a quite distinctive aspect. Instead the occurrence of epiphyseal plate-like cartilage is peculiar of the former.

The only effective line of treatment for malignant infantile osteopetrosis is hematopoietic stem cell transplantation. It has been shown to provide long-term disease-free periods for a significant percentage of those treated; can impact both hematologic and skeletal abnormalities; and has been used successfully to reverse the associated skeletal abnormalities.

Radiographs of at least one case with malignant infantile osteopetrosis have demonstrated bone remodeling and recanalization of medullar canals following hematopoietic stem cell transplantation. This favorable radiographic response could be expected within one year following the procedure - nevertheless, primary graft failure can prove fatal.

The disorder is progressive, with the ultimate severity of symptoms often depending on age of onset. In severe cases amputation has been performed when conservative measures such as physical therapy and regional anesthetics have been ineffective.

Ischiopatellar dysplasia is usually identified through radiographic evidence since its characteristic changes are most notable in radiographic tests that indicate delayed boneage or absent ossification. A full skeletal survey should be performed on any patient that has an absent or hypoplastic patellae since they could potentially have ischiopatellar dysplasia. Magnetic resonance imaging (MRI) is especially helpful in the diagnosis of ischiopatellar syndrome and is recommended when an individual affected by ischiopatellar dysplasia has a traumatic injury to the knee.

The differential diagnosis of malignant infantile osteopetrosis includes other genetic skeletal dysplasias that cause osteosclerosis. They are collectively known as osteosclerosing dysplasias. The differential diagnosis of genetic osteosclerosing dysplasias including infantile osteopetrosis has been tabulated and illustrated in literature citations.

- Neuropathic infantile osteopetrosis

- Infantile osteopetrosis with renal tubular acidosis

- Infantile osteopetrosis with immunodeficiency

- IO with leukocyte adhesion deficiency syndrome (LAD-III)

- Intermediate osteopetrosis

- Autosomal dominant osteopetrosis (Albers-Schonberg)

- Pyknodysostosis (osteopetrosis acro-osteolytica)

- Osteopoikilosis (Buschke–Ollendorff syndrome)

- Osteopathia striata with cranial sclerosis

- Mixed sclerosing bone dysplasia

- Progressive diaphyseal dysplasia (Camurati–Engelmann disease)

- SOST-related sclerosing bone dysplasias

Exact diagnosis remains widely built on precise history taking, with the characteristic clinical and radiographic skeletal features. Genetic diagnosis is based on DNA sequencing. Because plasma COMP levels are significantly reduced in patients with COMP mutations, such as pseudoachondroplasia, measuring plasma COMP levels has become a reliable means of diagnosing this and pathopysiologically similar disorders.

The most common locations are the shaft and epyphises of long bones (fibula and humerus) but the spine, metatarsal bones, and ilium have been involved as well. Radiologic examination evidences osteolytic areas with a lobulated framework comprising radiolucent and radiodense foci admixed to speckled calcification. Cortical destruction is a common finding with no soft tissue expansion in many cases. Histopathology of the lesion shows large areas of mature fibrous stroma undergoing hyaline cartilage metaplasia resulting in conspicuous lobules or gradual transformation into chondroid foci. Both hyaline cartilage and chondroid in turn undergo calcification and endochondral cancellous bone formation mimicking epiphyseal plate-like cartilage.

Differential diagnosis is concerned with fibrocartilaginous dysplasia of bone, desmoplastic fibroma, low-grade fibrosarcoma, chondromyxoid fibroma and low-grade chondrosarcoma.

A full account of imaging findings on radiography, bone scan, CT and magnetic resonance has been provided by Sumner et al.

Polyostotic fibrous dysplasia is a form of fibrous dysplasia affecting more than one bone.

McCune-Albright syndrome includes polyostotic fibrous dysplasia as part of its presentation.

One treatment that has been used is bisphosphonates.

The diagnosis of Nezelof syndrome will indicate a deficiency of T-cells, additionally in ascertaining the condition the following is done:

Different features of the dysostosis are significant. Radiological imaging helps confirm the diagnosis. During gestation (pregnancy), clavicular size can be calculated using available nomograms. Wormian bones can sometimes be observed in the skull.

Diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or by the identification of a heterozygous pathogenic variant in RUNX2 (CBFA1).

Biochemical studies reveal hypophosphatemia (low blood phosphate), elevated alkaline phosphatase and low serum 1, 25 dihydroxyvitamin D levels. Routine laboratory tests do not include serum phosphate levels and this can result in considerable delay in diagnosis. Even when low phosphate is measured, its significance is often overlooked. The next most appropriate test is measurement of urine phosphate levels. If there is inappropriately high urine phosphate (phosphaturia) in the setting of low serum phosphate (hypophosphatemia), there should be a high suspicion for tumor-induced osteomalacia. FGF23 (see below) can be measured to confirm the diagnosis but this test is not widely available.

Once hypophosphatemia and phosphaturia have been identified, a search for the causative tumor should begin. These are small and difficult to define. Gallium-68 DOTA-Octreotate (DOTA-TATE) positron emission tomography (PET) scanning is the best way to locate these tumors. If this scan is not available, other options include Indium-111 Octreotide (Octreoscan) SPECT/CT, whole body CT or MRI imaging.

Serum chemistries are identical in tumor-induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopepetidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF-23 gene will identify patients with ADHR.

Treatment of bone tumors is highly dependent on the type of tumor.

DNA testing is now the preferred method of establishing a diagnosis for MEN 2B, and is thought to be almost 100% sensitive and specific. Gordon et al. reported cases of a difference disease—the "multiple mucosal neuroma syndrome"—having the physical phenotype of MEN2B, but without variations in the RET gene and without malignancy.

MEN2B should be entertained as a diagnosis whenever a person is found to have either medullary thyroid carcinoma or pheochromocytoma. Before DNA testing became available, measurement of serum calcitonin was the most important laboratory test for MEN2B. Calcitonin is produced by the "C" cells of the thyroid, which, because they are always hyperplastic or malignant in MEN2B, produce more calcitonin than normal. Calcitonin levels remain a valuable marker to detect recurrence of medullary thyroid carcinoma after thyroidectomy.

Luxol fast blue staining identifies myelin sheathing of some fibers, and lesional cells react immunohistochemically for S-100 protein, collagen type IV, vimentin, NSE, and neural filaments. More mature lesions will react also for EMA, indicating a certain amount of perineurial differentiation. Early lesions, rich in acid mucopolysaccharides, stain positively with alcian blue. When medullary thyroid cancer is present, levels of the hormone calcitonin are elevated in serum and urine. Under the microscope, tumors may closely resemble traumatic neuroma, but the streaming fascicles of mucosal neuroma are usually more uniform and the intertwining nerves of the traumatic neuroma lack the thick perineurium of the mucosal neuroma. Inflammatory cells are not seen in the stroma and dysplasia is not present in the neural tissues.

Because kniest dysplasia can affect various body systems, treatments can vary between non-surgical and surgical treatment. Patients will be monitored over time, and treatments will be provided based on the complications that arise.

Men and women are affected in equal number., reflecting the fact that osteopoikilosis attacks indiscriminately. Additionally, the disease is often associated with melorheostosis, despite the apparent lack of correlation between melorheostosis and genetic heritability. It has been tied to LEMD3. Buschke-Ollendorff syndrome is a similar condition, which is also associated with LEMD3.

The differential diagnosis for this condition consists of acquired immune deficiency syndrome and severe combined immunodeficiency syndrome

Accurate assessment of plain radiographic findings remains an important contributor to diagnosis of pseudoachondroplasia. It is noteworthy that vertebral radiographic abnormalities tend to resolve over time. Epiphyseal abnormalities tend to run a progressive course. Patients usually suffer early-onset arthritis of hips and knees. Many unique skeletal radiographic abnormalities of patients with pseudoachondroplasia have been reported in the literature.

- Together with rhizomelic limb shortening, the presence of epiphyseal-metaphyseal changes of the long bones is a distinctive radiologic feature of pseudoachondroplasia.

- Hypoplastic capital femoral epiphyses, broad short femoral necks, coxa vara, horizontality of acetabular roof and delayed eruption of secondary ossification center of os pubis and greater trochanter.

- Dysplastic/hypoplastic epiphyses especially of shoulders and around the knees.

- Metaphyseal broadening, irregularity and metaphyseal line of ossification. These abnormalities that are typically encountered in proximal humerus and around the knees are collectively known as “rachitic-like changes”.

- Radiographic lesions of the appendicular skeleton are typically bilateral and symmetric.

- Oval shaped vertebrae with anterior beak originating and platyspondyly demonstrated on lateral radiographs of the spine.

- Normal widening of the interpedicular distances caudally demonstrated on anteroposterior radiographs of the dorsolumbar region. This is an important differentiating feature between pseudoachondroplasia and achondroplasia.

- Odontoid hypoplasia may occur resulting in cervical instability.

Initially, patients with neonatal or early-childhood onset diabetes are possible candidates for having Wolcott–Rallison syndrome. The other symptoms include the multiple epiphyseal dysplasia, osteopenia, intellectual disability, and hepatic and renal dysfunction. Patients with the symptoms that line up with Wolcott–Rallison syndrome can be suggested for genetics testing. The key way to test for this disease specifically is through genetic testing for the EIKF2AK3 mutation. Molecular genetic analysis can be done for the patient and the parents to test for de novo mutations or inherited. It can also show whether the patient's parents are heterozygotes or homozygotes for the normal phenotype. X-Rays can show bone age in relation to actual age. Typically the bond age is a few years less than the actual in the patients with WRS. Hypothyroidism is rare is WRS patients but can occur.

Without treatment, persons with MEN2B die prematurely. Details are lacking, owing to the absence of formal studies, but it is generally assumed that death in the 30s is typical unless prophylactic thyroidectomy and surveillance for pheochromocytoma are performed (see below). The range is quite variable, however: death early in childhood can occur, and it is noteworthy that a few untreated persons have been diagnosed in their 50s. Recently, a larger experience with the disease "suggests that the prognosis in an individual patient may be better than previously considered."

Thyroidectomy is the mainstay of treatment, and should be performed without delay as soon as a diagnosis of MEN2B is made, even if no malignancy is detectable in the thyroid. Without thyroidectomy, almost all patients with MEN2B develop medullary thyroid cancer, in a more aggressive form than MEN 2A. The ideal age for surgery is 4 years old or younger, since cancer may metastasize before age 10.

Pheochromocytoma - a hormone secreting tumor of the adrenal glands - is also present in 50% of cases. Affected individuals are encouraged to get yearly screenings for thyroid and adrenal cancer.

Because prophylactic thyroidectomy improves survival, blood relatives of a person with MEN2B should be evaluated for MEN2B, even if lacking the typical signs and symptoms of the disorder.The mucosal neuromas of this syndrome are asymptomatic and self-limiting, and present no problem requiring treatment. They may, however, be surgically removed for aesthetic purposes or if they are being constantly traumatized.

Treatment in fibrous dysplasia is mainly palliative, and is focused on managing fractures and preventing deformity. There are no medications capable of altering the disease course. Intravenous bisphosphonates may be helpful for treatment of bone pain, but there is no clear evidence that they strengthen bone lesions or prevent fractures. Surgical techniques that are effective in other disorders, such as bone grafting, curettage, and plates and screws, are frequently ineffective in fibrous dysplasia and should be avoided. Intramedullary rods are generally preferred for management of fractures and deformity in the lower extremities. Progressive scoliosis can generally be managed with standard instrumentation and fusion techniques. Surgical management in the craniofacial skeleton is complicated by frequent post-operative FD regrowth, and should focus on correction of functional deformities. Prophylactic optic nerve decompression increases the risk of vision loss and is contraindicated.

Managing endocrinopathies is a critical component of management in FD. All patients with fibrous dysplasia should be evaluated and treated for endocrine diseases associated with McCune–Albright syndrome. In particular untreated growth hormone excess may worsen craniofacial fibrous dysplasia and increase the risk of blindness. Untreated hypophosphatemia increases bone pain and risk of fractures.

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