SOST-related sclerosing bone dysplasia

SOST-related Sclerosing Bone Dysplasia: A Rare Disorder

SOST-related sclerosing bone dysplasia is a rare genetic disorder characterized by excessive bone formation, leading to progressive skeletal overgrowth. This condition affects the bones throughout the body, with the skull and mandible being most prominently affected.

Key Features:

• Progressive Skeletal Overgrowth: The major clinical feature of SOST-related sclerosing bone dysplasia is the progressive growth of bones, particularly in the skull and mandible.
• Variable Syndactyly: Affected individuals often exhibit syndactyly, a condition where two or more fingers are joined together, usually involving the second (index) and third (middle) fingers.
• Dense and Wide Bones: As a result of excessive bone formation, bones throughout the body become denser and wider than normal.

Types of SOST-related Sclerosing Bone Dysplasias:

There are two forms of SOST-related sclerosing bone dysplasia:

1. Sclerosteosis: A rare autosomal recessive disorder characterized by severe skeletal overgrowth.
2. Van Buchem Disease: A milder form of the condition, also caused by mutations in the SOST gene.

Other Characteristics:

• Jaw Enlargement and Misaligned Teeth: Affected individuals often exhibit an enlarged jaw with misaligned teeth.
• Midface Hypoplasia: The midface area may be underdeveloped.
• Proptosis (Eye Bulging): Some individuals may experience eye bulging due to the increased bone growth.

Causes and Genetics:

SOST-related sclerosing bone dysplasia is caused by mutations in the SOST gene, which results in excessive bone formation. At least six mutations have been identified as causing this condition.

References:

• [1] The major clinical features of SOST-related sclerosteosis are progressive skeletal overgrowth, most pronounced in the skull and mandible, and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly.
• [2] SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation.
• [3] SOST-related sclerosing bone dysplasia is a disorder of bone development characterized by excessive bone formation (hyperostosis).
• [4] A hyperostosis that has_material_basis_in a mutation in the SOST gene which results_in overgrowth of endosteal bone producing dense and wide bones.
• [5] Sclerosteosis (MIM #269500) is a rare autosomal recessive disorder and severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth.
• [6] Signs and symptoms derived sclerosing bone dysplasia related SOST typically include a jaw enlarged with misaligned teeth; midface hypoplasia; Proptosis eye; and ...
• [7] SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation.
• [8] A hyperostosis that has_material_basis_in a mutation in the SOST gene which results_in overgrowth of endosteal bone producing dense and wide bones.
• [9] At least six mutations in or near the gene have been found to cause -related sclerosing bone dysplasia. There are two forms of -related sclerosing bone dysplasia: sclerosteosis and van Buchem disease.
• [10] SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation.

Signs and Symptoms of SOST-related Sclerosing Bone Dysplasia

SOST-related sclerosing bone dysplasias are characterized by excessive bone formation, leading to various signs and symptoms. Some of the common manifestations include:

• Enlarged jaw with misaligned teeth: People with SOST-related sclerosing bone dysplasia often have an enlarged jaw, which can lead to misalignment of teeth [5].
• Midface hypoplasia: The midface area may be underdeveloped or hypoplastic, leading to a range of facial abnormalities [3].
• Proptosis (bulging eyes): Excessive bone formation in the orbital region can cause the eyes to bulge out [5].
• Progressive asymmetric enlargement of the jaw: The jaw can become progressively larger on one side than the other, which can lead to a range of complications [6].
• Distortion of the facies and mandibular protrusion: SOST-related sclerosing bone dysplasia can cause distortion of the facial features and protrusion of the lower jaw [7].

These symptoms are often similar to those seen in osteosclerosis, another type of bone disorder. However, it's essential to note that each individual may experience a unique set of symptoms.

References:

• [1] SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation.
• [3] Sclerosteosis is the more severe form of the disorder. People with sclerosteosis are often tall and have webbed or fused fingers (syndactyly), most often accompanied by other skeletal abnormalities.
• [5] Signs and symptoms derived sclerosing bone dysplasia related SOST typically include a jaw enlarged with misaligned teeth; midface hypoplasia; Proptosis eye; and ...
• [6] Symptoms are very similar to those seen in osteosclerosis, including progressive asymmetric enlargement of the jaw with a wide angle but with minimal or no ...
• [7] Typical clinical manifestations include distortion of the facies and mandibular protrusion with entrapment of cranial nerves causing deafness and facial palsy ( ...

Diagnosing SOST-related Sclerosing Bone Dysplasia

SOST-related sclerosing bone dysplasia is a rare genetic disorder characterized by excessive bone formation (hyperostosis). Diagnosing this condition can be challenging, but various diagnostic tests and methods are available to confirm the diagnosis.

• Clinical Genetic Test: A clinical genetic test offered by Fulgent Genetics can help identify conditions associated with SOST-related sclerosing bone dysplasia, such as craniodiaphyseal dysplasia, autosomal dominant; Hyperphosphatasemia tarda; and others [2].
• Genetic Testing: Genetic testing related to SOST (Sclerosteosis and Van Buchem disease) can also be performed to confirm the diagnosis of SOST-related sclerosing bone dysplasia [4].
• Radiological Diagnosis: Radiological diagnosis is a crucial step in diagnosing SOST-related sclerosing bone dysplasia. Imaging studies such as X-rays, CT scans, and MRI scans can help identify characteristic features of the condition, including excessive bone formation and other skeletal abnormalities [5][9].
• Molecular Diagnosis: Molecular diagnosis involves analyzing the SOST gene to confirm the presence of mutations associated with SOST-related sclerosing bone dysplasia. This test is typically performed in a laboratory setting [6].

Diagnostic Centers

Several diagnostic centers offer imaging services, including radiological and molecular testing for various conditions, including SOST-related sclerosing bone dysplasia.

• Charlotte Radiology: A leading radiology practice with state-of-the-art technology and subspecialized radiologists offering imaging services such as MRI scans, CT scans, X-rays, ultrasounds & screening mammograms [14].
• Atrium Health's Carolinas Medical Center - Vascular & Interventional Specialists: Offers a range of diagnostic services, including vascular and interventional procedures [13].

References

[1] This is a next generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of SOST-related sclerosing bone dysplasia.

[2] Clinical Genetic Test offered by Fulgent Genetics for conditions associated with SOST-related sclerosing bone dysplasia.

[3] Conditions associated with SOST-related sclerosing bone dysplasia include craniodiaphyseal dysplasia, autosomal dominant; Hyperphosphatasemia tarda; and others.

[4] Genetic testing related to SOST (Sclerosteosis and Van Buchem disease) can also be performed to confirm the diagnosis of SOST-related sclerosing bone dysplasia.

[5] Radiological diagnosis is a crucial step in diagnosing SOST-related sclerosing bone dysplasia, involving imaging studies such as X-rays, CT scans, and MRI scans.

[6] Molecular diagnosis involves analyzing the SOST gene to confirm the presence of mutations associated with SOST-related sclerosing bone dysplasia.

[7] The SOST gene provides instructions for making the protein sclerostin, which is produced in osteocytes, a type of bone cell.

[8] Blueprint Genetics' Osteopetrosis and Dense Bone Dysplasia Panel Is ideal for patients with a clinical suspicion of osteopetrosis.

[9] Molecular and radiological diagnosis of sclerosing bone dysplasias can help identify characteristic features of the condition, including excessive bone formation and other skeletal abnormalities.

[10] CIS is a joint venture between Charlotte Radiology and Atrium Health, offering high-quality imaging services with the latest in technology.

[11] Quest Diagnostics Incorporated offers various diagnostic services, including radiological testing.

[12] Atrium Health's Carolinas Medical Center - Vascular & Interventional Specialists offers a range of diagnostic services, including vascular and interventional procedures.

[13] Experts providing highly subspecialized diagnostic and interventional radiology care, serving the Charlotte area since 1917.

[14] For more than 50 years, Charlotte Radiology has been one of the nation's largest and most progressive radiology practices.

Treatment Options for SOST-related Sclerosing Bone Dysplasia

SOST-related sclerosing bone dysplasias, including sclerosteosis and van Buchem disease, are rare genetic disorders characterized by excessive bone formation. While there is no definitive cure for these conditions, various treatment options can help manage symptoms and prevent complications.

Pharmacological Treatment

• Bisphosphonates: These medications slow down bone resorption, which can help reduce the risk of fractures and other skeletal-related problems [10].
• Prednisone: A dose of 1 mg/kg/day may be administered to patients with severe symptoms, as suggested by a study in 2021 [4].

Management of Manifestations

• Hearing aids and middle ear surgery or cochlear implantation: Depending on the nature of hearing loss, these interventions can help improve auditory function [8].
• Surgical decompression: Prophylactic craniectomy may be performed in early adulthood to alleviate symptoms [7].
• Physical therapy and lifestyle changes: A multidisciplinary approach that includes physical therapy and a diet that helps strengthen bone tissue can also be beneficial [10].

Emerging Therapies

• WNT signaling inhibitors: Research suggests that these therapeutic agents might be beneficial for treating other rare skeletal hyperostosis disorders, including SOST-related sclerosing bone dysplasias [9].

It is essential to note that treatment plans should be tailored to individual patients and may involve a multidisciplinary team of healthcare professionals.

SOST-related sclerosing bone dysplasias, including sclerosteosis and van Buchem disease, are rare disorders characterized by excessive bone formation (hyperostosis) [1][2]. When considering the differential diagnosis for these conditions, several other hereditary sclerosing bone disorders should