Because this genetic anomaly is genetically linked, genetic counseling may be the only way to decrease occurrences of Cherubism. The lack of severe symptoms in the parents may be the cause of failure in recognizing the disorder. The optimal time to be tested for mutations is prior to having children. The disorder results from a genetic mutation, and this gene has been found to spontaneously mutate. Therefore, there may be no prevention techniques available.

The chemical imbalance is usually diagnosed when dental abnormalities are found. These abnormalities include premature deciduous teeth and abnormal growth of permanent teeth due to displacement by cysts and lesions. The only definite way to correctly diagnose the condition is by sequence analysis of the SH3BP2 gene. The gene has been found to have missense mutation in exon 9. Initial study of the patient is usually conducted using x-ray and CT scans. Neurofibromatosis may resemble Cherubism and may accompany the condition. Genetic testing is the final diagnosis tool.

Diagnosis should be based on the clinical and radiographic findings and a genetic analysis can be assessed.

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.

One person in every 100,000 is affected. Ollier disease is not normally diagnosed until toddler years because it is not very visible.

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.

The deformities are managed surgically to preserve the function of the limb.

Many features of gerodermia osteodysplastica (GO) and another autosomal recessive form of cutis laxa, wrinkly skin syndrome (WSS, ""), are similar to such an extent that both disorders were believed to be variable phenotypes of a single disorder.

Several delineating factors, however, suggest that gerodermia osteodysplastica and wrinkly skin syndrome are distinct entities, but share the same clinic spectrum.

While the prevailing feature of wrinkly, loose skin is more localized with GO, it is usually systemic, yet eases in severity with age during the course of WSS. Also, as the fontanelles ("soft spots") are usually normal on the heads of infants with GO, they are often enlarged in WSS infants.

While WSS is associated with mutations of genes on chromosomes 2, 5, 7, 11 and 14; GO has been linked to mutations in the protein GORAB. A serum sialotransferrin type 2 pattern, also observed with WSS, is not present in GO patients.

But perhaps the most notable feature, differentiating GO from WSS and similar cutis laxa disorders, is the age-specific metaphyseal peg sometimes found in GO-affected long bone, near the knee. Not appearing until around age 4–5, then disappearing by physeal closure, this oddity of bone is thought to represent a specific genetic marker unique to GO and its effects on bone development.

CDPX1 activity may be inhibited by warfarin because it is believed that ARSE has enzymatic activity in a vitamin K producing biochemical pathway. Vitamin K is also needed for controlling binding of calcium to bone and other tissues within the body.

Since elevated PGE2 levels are correlated with PDP, urinary PGE2 can be a useful biomarker for this disease. Additionally, HPGD mutation analyses are relatively cheap and simple and may prove to be useful in early investigation in patients with unexplained clubbing or children presenting PDP-like features. Early positive results can prevent expensive and longtime tests at identifying the pathology.

For the follow-up of PDP disease activity, bone formation markers such as TAP, BAP, BGP, carbodyterminal propeptide of type I procallagen or NTX can play an important role. Other biomarkers that can be considered are IL-6 and receptor activator of NF-κB ligand (RANKL), which are associated with increased bone resorption in some patients. However, further investigation is needed to confirm this use of disease monitoring.

Prostaglandin E2 may also be raised in patients with lung cancer and finger clubbing. This may be related to raised levels of cyclooxygenase-2, an enzyme involved in the metabolism of prostaglandins. A similar association has been noted in cystic fibrosis.

Pacman dysplasia (alternatively known as epiphyseal stippling with osteoclastic hyperplasia) is a lethal autosomal recessive skeletal dysplasia. The dysplasia is present during fetal development.

The easiest way to diagnose PDP is when pachydermia, finger clubbing and periostosis of the long bones are present. New bone formation under the periosteum can be detected by radiographs of long bones. In order diagnose PDP, often other diseases must be excluded. For example, to exclude secondary hypertrophic osteoarthropathy, any signs of cardiovascular, pulmonary, hepatic, intestinal and mediastinal diseases must be absent. MRI and ultrasound also have characterictic findings.

Skin biopsy is another way to diagnose PDP. However, it is not a very specific method, because other diseases share the same skin alterations with PDP, such as myxedema and hypothyroidism. In order to exclude these other diseases, hormonal studies are done. For example, thyrotropin and growth hormone levels should be examined to exclude thyroid acropachy and acrome. However, skin biopsy helps to diagnose PDP in patients without skin manifestations.

When clubbing is observed, it is helpful to check whether acroosteolysis of distal phalanges of fingers is present. This is useful to diagnose PDP, because the combination of clubbing and acroosteolysis is only found in PDP and Cheney’s syndrome.

Ultrasound remains as one of the only effective ways of prenatally diagnosing Larsen syndrome. Prenatal diagnosis is extremely important, as it can help families prepare for the arrival of an infant with several defects. Ultrasound can capture prenatal images of multiple joint dislocations, abnormal positioning of legs and knees, depressed nasal bridge, prominent forehead, and club feet. These symptoms are all associated with Larsen syndrome, so they can be used to confirm that a fetus has the disorder.

The activity of arylsulfatase E can be measured with the substrate 4-methylumbelliferyl sulfate.

Spondyloepimetaphyseal dysplasia, Pakistani type is a form of spondyloepimetaphyseal dysplasia involving "PAPSS2" (also known as "ATPSK2"). The condition is rare.

Radiographic features include delayed epiphyseal ossification at the hips and knees, platyspondyly with irregular end plates and narrowed joint spaces, diffuse early osteoarthritic changes (in the spine and hands), mild brachydactyly and mild metaphyseal abnormalities which predominantly involve the hips and knees.

Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae, is an autosomal recessive congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.

Some affected individuals are born with an inward- and downward-turning foot (a clubfoot). An abnormality of the kneecap called a double-layered patella is also relatively common. Although some people with recessive multiple epiphyseal dysplasia have short stature as adults, most are of normal height. The incidence is unknown as many cases are not diagnosed due to mild symptoms.

Plain film

often seen as a lobulated, eccentric radiolucent lesion

long axis parallel to long axis of long bone

no periosteal reaction (unless a complicating fracture present)

geographic bone destruction: almost 100%

well defined sclerotic margin: 86%

there can be presence of septations (pseudotrabeculation): 57% 2

there can be presence of matrix calcification in a small proportion of cases: 12.5%1

MRI

MR features are often not particularly specific. Signal characteristics include

T1 - low signal

T1 C+ (Gd) -

the majority (~70%) tend to show peripheral nodular enhancement

~ 30% diffuse contrast enhancement and this can be either homogeneous or heterogeneous 19

T2 - high signal

Bone scan

A scintigraphic "doughnut sign" has been described in this tumour type 11. However, this is very non-specific and can be found in a plethora of other bone lesions.

Symptomatic individuals should be seen by an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs). Although there is no cure, surgery is sometimes used to relieve symptoms. Surgery may be necessary to treat malformation of the hip (osteotomy of the pelvis or the collum femoris) and, in some cases, malformation (e.g., genu varum or genu valgum). In some cases, total hip replacement may be necessary. However, surgery is not always necessary or appropriate.

Sports involving joint overload are to be avoided, while swimming or cycling are strongly suggested. Cycling has to be avoided in people having ligamentous laxity.

Weight control is suggested.

The use of crutches, other deambulatory aids or wheelchair is useful to prevent hip pain. Pain in the hand while writing can be avoided using a pen with wide grip.

They are benign lesions and malignant degeneration is rare. They are usually treated with curettage which however have a high recurrence rate of 25%. As such if an en-bloc resection is possible this is advisable

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.

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.

Mutations in the SLC26A2 (DTDST) gene, located at human chromosome 5q32-33.1, are the cause of ARMED. It is considered a milder disorder within a spectrum of skeletal disorders caused by mutations in the gene, which encodes a protein that is essential for the normal development of cartilage and its conversion to bone. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in associated skeletal maldevelopment.

The disorder is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome (chromosome 5 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

While Larsen syndrome can be lethal if untreated, the prognosis is relatively good if individuals are treated with orthopedic surgery, physical therapy, and other procedures used to treat the symptoms linked with Larsen syndrome.

In 1983 Heffez and colleagues published a case report in which they suggested eight criteria for a definitive diagnosis of Gorham's disease:

- Positive biopsy with the presence of angiomatous tissue

- Absence of cellular atypia

- Minimal or no osteoblastic response or dystrophic calcifications

- Evidence of local bone progressive osseous resorption

- Non-expansile, non-ulcerative lesions

- No involvement of viscera

- Osteolytic radiographic pattern

- Negative hereditary, metabolic, neoplastic, immunologic, or infectious etiology.

In the early stages of the disease x-rays reveal changes resembling patchy osteoporosis. As the disease progresses bone deformity occurs with further loss of bone mass and, in the tubular bones (the long bones of the arms and legs), a concentric shrinkage is often seen which has been described as having a "sucked candy" appearance. Once the cortex (the outer shell) of the bone has been disrupted, vascular channels may invade adjacent soft tissues and joints. Eventually, complete or near-complete resorption of the bone occurs and may extend to adjacent bones, though spontaneous arrest of bone loss has been reported on occasion. Throughout this process, as the bone is destroyed it is replaced by angiomatous and/or fibrous tissue.

Often Gorham's disease is not recognized until a fracture occurs, with subsequent improper bone healing. The diagnosis essentially is one of exclusion and must be based on combined clinical, radiological, and histopathological findings. X-rays, CT scans, MRIs, ultrasounds, and nuclear medicine (bone scans) are all important tools in the diagnostic workup and surgical planning, but none have the ability alone to produce a definitive diagnosis. Surgical biopsy with histological identification of the vascular or lymphatic proliferation within a generous section of the affected bone is an essential component in the diagnostic process.

Recognition of the disease requires a high index of suspicion and an extensive workup. Because of its serious morbidity, Gorham's must always be considered in the differential diagnosis of osteolytic lesions.