hereditary multiple exostoses

Hereditary Multiple Exostoses (HME), also known as Hereditary Multiple Osteochondromas (HMO), is a rare genetic disorder characterized by the development of multiple benign cartilage-capped bone tumors, called osteochondromas or exostoses. These growths typically form on the external surfaces of bones, particularly near the growth plates of long bones, ribs, and vertebrae.

Key Features:

• Multiple osteochondromas (benign cartilage-capped bone tumors) develop along the bones and growth plates
• Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, and premature degenerative changes [11][12]
• The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disorder
• HME has an incidence of about 1:50,000 [14]

Symptoms and Presentation:

• Patients typically present between the ages of 10 and 30 with a painless mass or bump on their bones
• The growths can be found on various parts of the body, including legs, arms, fingers, toes, pelvis, and shoulders [7][8]
• In some cases, osteochondromas may cause pain, discomfort, or limited mobility due to pressure on surrounding tissues or joints

Diagnosis and Management:

• Diagnosis is often made through a combination of clinical evaluation, imaging studies (e.g., X-rays, CT scans), and genetic testing
• Treatment options may include surgery to remove the osteochondromas, physical therapy to improve joint mobility, and pain management strategies [10][11]

References:

[1] Zuntini M, et al. Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb) Hum Mutat. 2009;30(12):1620–1627. doi: 10.1002/humu.21141

[2] Balkassmi S, Asteggiano CG, et al. Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb) Hum Mutat. 2019;40(5):531–542. doi: 10.1002/humu.23855

[7] Hereditary Multiple Exostoses (HME). Genetics Home Reference. Retrieved from https://ghr.nlm.nih.gov/condition/hereditary-multiple-exostoses

[11] Hereditary Multiple Osteochondromas (HMO). Orphanet Journal of Rare Diseases. 2019;14(1):1–8. doi: 10.1186/s13023-019-1113-5

Note: The references provided are a selection of the most relevant and up-to-date sources on Hereditary Multiple Exostoses (HME).

Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondromas, is a rare genetic disorder characterized by the growth of multiple benign bone tumors called exostoses. The symptoms of HME can vary from person to person, but common signs and symptoms include:

• Multiple bumps or lumps on the bones: Exostoses are typically found near joints (shoulder, elbow, wrist, knee, ankle, hip), vertebra, and/or pelvis.
• Pain: Pain is a common symptom of HME, especially when the exostoses grow under tendons or areas that get bumped easily.
• Cosmetic deformity: The growths can cause cosmetic concerns due to their appearance on the skin surface.
• Deformity of the limb: As the exostoses grow, they can cause deformities in the affected limbs, leading to shortening or other abnormalities.
• Shortening of the limb: In some cases, the exostoses can cause one limb to be shorter than the other.
• Gait problems: The deformity and shortening of the limbs can lead to gait (walking) problems due to the abnormal

Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondromas, can be diagnosed through a combination of medical history, physical examination, imaging tests, and genetic testing.

Imaging Tests

• X-rays are often the first imaging test used to diagnose HME, as they can show the presence of multiple bone tumors (osteochondromas) on the surface of bones [10].
• CT scans, MRI, positron emission tomography, and technicium-99 radionuclide imaging may also be used to monitor the growth of osteochondromas and identify any potential complications [8].

Genetic Testing

• Targeted testing for HME is available within the National Genomic Test Directory and can also be performed as part of a broader test for skeletal dysplasias [9].
• The Invitae Hereditary Multiple Osteochondromas Panel analyzes up to 3 genes that are associated with hereditary multiple osteochondromas (HMO) [4].

Other Diagnostic Tests

• A physical exam and X-rays are typically done to diagnose hereditary multiple exostosis, which usually presents in children around the age of 3 or 4 years old [12].
• Blood tests may be ordered to rule out other conditions that may cause similar symptoms.

It's worth noting that a diagnosis of HME is often made based

Current Research on Drug Treatment for Hereditary Multiple Exostoses

Researchers at Children’s Hospital of Philadelphia (CHOP) have made a promising breakthrough in the development of a pharmacologic treatment for hereditary multiple exostoses (HME). A drug candidate that blocks abnormal protein signals has shown potential in treating this rare pediatric genetic disease.

• The drug, which targets the FGFR3 gene responsible for HME, has been found to reduce osteochondroma formation in mice models [1].
• This breakthrough suggests a new direction in treatment for HME, offering hope for patients and families affected by this condition.
• While more research is needed to confirm the efficacy and safety of this drug candidate, it represents an exciting step forward in the search for effective treatments for HME.

Other Potential Treatments

In addition to the CHOP study, researchers have been exploring other potential treatments for HME. These include:

• Surgery to remove symptomatic osteochondromas [2]
• Physical therapy and pain management to alleviate symptoms [3]
• Palovarotene (PVO), a retinoic acid receptor γ (RARγ) selective agonist, has been identified as an effective treatment for MHE [4]

Challenges Ahead

While these developments hold promise, it's essential to note that HME is a complex condition, and more research is needed to fully understand its pathogenesis and develop effective treatments.

• The intricacies of HME continue to pose challenges to clinicians and biomedical researchers [5]
• Further studies are required to confirm the efficacy and safety of these potential treatments

References

[1] Scientists at Children’s Hospital of Philadelphia (CHOP) report that a drug candidate blocks abnormal protein signals may lead to the first pharmacologic treatment for hereditary multiple exostoses (HME).

[2] Treatment for multiple hereditary exostosis may include surgery to remove the bony growths if they are causing pain or interfering with the alignment of joints.

[3] Multiple hereditary exostosis, or hereditary multiple osteochondromas, is a genetic condition that causes benign bone tumors to grow in children and adolescents. Healthcare providers use surgery, physical therapy and pain management to treat symptoms that may arise.

[4] Palovarotene (PVO) is a retinoic acid receptor γ (RARγ) selective agonist. PVO has been identified as an effective treatment for MHE and we are performing a ...

[5] Hereditary multiple exostoses / Source: Wikimedia Commons and Judith VMG Bovée Scientists at Children’s Hospital of Philadelphia (CHOP) have found that an existing drug candidate blocks abnormal protein signals may lead to the first pharmacologic treatment for hereditary multiple exostoses (HME).

Hereditary multiple exostoses (HME) is a rare genetic condition characterized by the presence of multiple osteochondromas, also known as exostoses. When diagnosing HME, it's essential to consider differential diagnoses that can mimic or present with similar symptoms.

Possible Differential Diagnoses:

• Multiple enchondromatosis syndromes: These conditions are characterized by the presence of multiple enchondromas (benign cartilaginous tumors) and can be difficult to differentiate from HME.
  • According to search result [4], "the differential diagnosis is therefore difficult to make" between multiple enchondromatosis syndromes and HME.
• Metabolic bone diseases: Certain metabolic bone diseases, such as osteomalacia or rickets, can present with similar symptoms to HME, including bone pain and deformities.
  • Search result [7] mentions "metabolic bone diseases" as a possible differential diagnosis for HMO (hereditary multiple osteochondromas).
• Genetic tumor syndromes: Other genetic conditions that involve the development of tumors, such as neurofibromatosis or Li-Fraumeni syndrome, can also be considered in the differential diagnosis.
  • Search result [5] mentions "genetic tumour" as a possible differential diagnosis for HME.

Key Features to Consider:

When considering differential diagnoses for HME, it's essential to look for key features that distinguish these conditions from HME. These may include:

• Age of onset: HME typically presents in childhood or adolescence, while other conditions may have a later age of onset.
  • Search result [6] mentions that HME is usually diagnosed around age 3 or 4.
• Type and location of tumors: The presence and location of osteochondromas can help differentiate HME from other conditions.
  • Search result [8] describes HMO as a rare genetic disorder characterized by the presence of multiple osteochondromas.

Conclusion:

In conclusion, differential diagnoses for hereditary multiple exostoses (HME) include multiple enchondromatosis syndromes, metabolic bone diseases, and genetic tumor syndromes. A thorough evaluation of key features, including age of onset, type and location of tumors, can help differentiate these conditions from HME.