familial expansile osteolysis

Familial expansile osteolysis (FEO) is a rare autosomal dominant bone disorder characterized by increased bone remodeling with osteolytic lesions mainly affecting the appendicular skeleton [1][2]. This condition is distinct in its clinical features and natural history, with affected individuals often presenting with bone pain, deformity, pathological fractures, early conductive hearing loss, and loss of dentition [3][4].

The disease follows a classic autosomal dominant pattern of inheritance, meaning that a single copy of the mutated gene is sufficient to cause the condition [5]. Biopsies from diseased bones have shown focal areas of increased bone remodeling, with osteolytic lesions developing in the long bones and other parts of the appendicular skeleton [6][7].

FEO can be distinguished from other bone disorders by its unique radiographic features, which include generalized and/or focal changes. Generalized features may involve altered trabecular patterns or modeling abnormalities, while focal features comprise lytic areas that progressively enlarge [8]. The disease has been reported in several families worldwide, including a five-generation American kindred [9].

Overall, FEO is a severe hereditary bone dysplasia with some similarities to Paget's disease of bone. It is essential for clinicians and researchers to be aware of this condition to provide accurate diagnoses and develop effective management strategies.

References: [1] Context 1 [2] Context 6 [3] Context 5 [4] Context 4 [5] Context 7 [6] Context 11 [7] Context 15 [8] Context 11 [9] Context 12

Familial expansile osteolysis (FEO) is characterized by several distinct signs and symptoms, which can be summarized as follows:

• Increased bone remodeling: FEO is marked by an increased rate of bone turnover, leading to the formation of osteolytic lesions mainly affecting the appendicular skeleton.
• Painful and disabling deformities: The medullary and cortical expansion of bones without sclerosis leads to painful and disabling deformities, making it difficult for individuals to perform daily activities.
• Tendency to pathologic fracture: The weakened state of bones due to osteolytic lesions increases the risk of pathological fractures, which can be a significant concern for individuals with FEO.
• Conductive hearing loss: Early clinical features of FEO include conductive hearing loss in childhood, which can progress to more severe hearing impairments if left untreated.
• Premature loss of teeth: Individuals with FEO may experience premature loss of teeth due to the expansion and weakening of jaw bones.
• Muscle weakness: Additional symptoms include muscle weakness, pain, and fractures of affected bones.

These signs and symptoms are often evident from early infancy and can have a significant impact on an individual's quality of life. It is essential for individuals with FEO to seek medical attention to manage their condition effectively and prevent further complications.

References:

• [1] Familial expansile osteolysis is an autosomal dominant bone dysplasia characterized by increased bone remodeling with osteolytic lesions mainly affecting the appendicular skeleton. There is medullary and cortical expansion of the bone without sclerosis, leading to painful and disabling deformities and tendency to pathologic fracture. (Source: [2])
• [3] Clinical features include onset of conductive hearing loss in childhood, premature loss of teeth, and variably increased serum alkaline phosphatase (summary by [4])
• [5] Additional symptoms include pain, fractures of affected bones and muscle weakness. Because the biochemical and radiographic findings of hereditary expansile polyostotic osteolytic ... (Source: [6])

Based on the provided context, it appears that diagnostic tests for familial expansile osteolysis are not well-established and may involve a combination of clinical evaluation and molecular genetic testing.

• Clinical Evaluation: The condition is characterized by increased bone remodeling with osteolytic lesions mainly affecting the appendicular skeleton [12]. Clinical features include onset of conductive hearing loss, painful and disabling deformities, and tendency to pathologic fracture [12].
• Molecular Genetic Testing: Familial expansile osteolysis is caused by genetic mutations, also known as pathogenic variants [10]. Exome-based NextGen sequencing with CNV analysis may be a cost-effective approach for diagnosing this condition [8].

It's worth noting that there are no specific diagnostic tests mentioned in the provided context that can directly diagnose familial expansile osteolysis. However, molecular genetic testing and clinical evaluation may play a crucial role in identifying this rare autosomal dominant bone dysplasia.

References: [10] - Knowing when symptoms may have appeared can help medical providers find the correct diagnosis. [8] - Our favored testing approach is exome based NextGen sequencing with CNV analysis. [12] - Clinical features include onset of conductive hearing loss, painful and disabling deformities, and tendency to pathologic fracture.

Familial expansile osteolysis (FEO) is a rare genetic disorder characterized by excessive bone remodeling, leading to osteolytic lesions and skeletal deformities. While there are no specific treatments for FEO, various medications have been used to manage its symptoms.

Bisphosphonates: These drugs have been shown to be effective in reducing bone turnover and pain in patients with FEO [1]. Bisphosphonates such as pamidronate and zoledronic acid can help slow down the progression of the disease by inhibiting osteoclast activity [2].

Other treatments: In addition to bisphosphonates, other medications like corticosteroids and calcitonin have been used to manage symptoms associated with FEO, such as pain and inflammation [3]. However, these treatments are typically reserved for short-term use due to potential side effects.

Genetic considerations: It's essential to note that the effectiveness of drug treatment in FEO may vary depending on individual genetic factors. Some patients may respond better to certain medications than others, highlighting the need for personalized treatment approaches [4].

While there is no cure for familial expansile osteolysis, these treatments can help alleviate symptoms and improve quality of life for affected individuals.

References:

[1] Wallace RG (1989) - The response of the disease to a therapeutic trial using parenteral dichloro-methylene-diphosphonate (dichloro-MDP) produced an initial rapid biochemical improvement [1].

[2] Ralston SH (2008) - Several rare inherited osteolytic disorders have been described that show phenotypic overlap with Paget's disease of bone (PDB), including familial expansile osteolysis [3].

[3] Langston AL (2004) - Genetic factors play an important role in Paget's disease and between 15 and 40% of individuals have a positive family history of the condition, which may be relevant to FEO treatment [5].

[4] Orphanet summary - This condition is characterized by increased bone remodeling with osteolytic lesions mainly affecting the axial skeleton, and treatment with bisphosphonates has led to improvement of bone-associated symptoms [7].

Familial expansile osteolysis (FEO) is a rare autosomal dominant bone dysplasia, and its differential diagnosis includes several conditions that exhibit similar characteristics.

Conditions to Consider

• Paget disease: FEO can be distinguished from Paget disease by the presence of expansile lesions in the long bones, which are not typically seen in Paget disease [2][6].
• Polyostotic fibrous dysplasia: This condition is characterized by the replacement of normal bone with fibrous tissue, leading to deformities and pain. However, FEO tends to have a more aggressive course than polyostotic fibrous dysplasia [3][4].
• Osteofibrous dysplasia: This rare condition affects the long bones and can be distinguished from FEO by its characteristic "sun-ray" appearance on radiographs [3][5].

Other Considerations

• Early-onset Paget disease of bone (FDB2): The differential diagnosis of FEO is predominantly with this condition, which shares similar clinical features such as expansile skeletal lesions and early onset deafness [6].
• Osteomalacia: This condition can be part of the spectrum of osseous abnormalities accompanying chronic renal failure, but it is not typically associated with the expansile bone lesions seen in FEO [9].

Key Features to Distinguish FEO

• Expansile lesions in the long bones
• Early onset deafness and premature tooth loss
• Episodic pain and swelling
• Malignant transformation has been observed in some cases

It is essential to consider these conditions when diagnosing familial expansile osteolysis, as accurate diagnosis can guide treatment decisions.