metachondromatosis

Metachondromatosis: A Rare Bone Disorder

Metachondromatosis (MC) is a rare bone disorder characterized by the presence of both multiple enchondromas and osteochondroma-like lesions [1][2]. This condition affects the growth of bones, leading to the formation of tumors on and within bones.

Key Features of Metachondromatosis

• Age of Onset: The first signs of MC occur during the first decade of life [12].
• Bone Affected: MC primarily affects tubular bones, although it can also involve the vertebrae, small joints, and flat bones [10][12].
• Tumor Formation: Metachondromatosis is characterized by exostoses (osteochondromas), commonly of the hands and feet, and enchondromas of long bone metaphyses and iliac crests [2][5][13].

Genetic Basis

Metachondromatosis is caused by a heterozygous mutation in the PTPN11 gene on chromosome 12q24 [2]. This genetic mutation leads to the loss of function of the PTPN11 gene, resulting in the formation of tumors on and within bones.

Other Similar Conditions

MC is distinct from other similar conditions such as multiple osteochondromas and hereditary multiple exostoses [11].

In summary, metachondromatosis is a rare bone disorder characterized by the presence of both multiple enchondromas and osteochondroma-like lesions. It affects the growth of bones, leading to the formation of tumors on and within bones, and is caused by a genetic mutation in the PTPN11 gene.

References: [1] Context result 2 [2] Context result 2 [3] Context result 10 [4] Context result 12 [5] Context result 13 [6] Context result 14

Metachondromatosis, also known as hereditary multiple osteochondromas (HMO), is a rare genetic disorder that affects bone growth. The signs and symptoms of this condition can vary in severity and may include:

• Bony tumors: Metachondromatosis is characterized by the presence of bony tumors, called exostoses or osteochondromas, which are covered with cartilage. These tumors typically appear in the growth zones (metaphyses) of the long bones adjacent to the areas where tendon and muscles attach to the bone [1].
• Osteochondromas: Osteochondromas are small, benign tumors that occur near the ends of long bones. They can be found in the hands and feet, predominantly in digits and toes, as well as in other parts of the body [2-4].
• Enchondromas: Enchondromas are cartilage-based tumors that can occur within the bone itself. In metachondromatosis, enchondromas typically involve the iliac crests and metaphyses of long bones [3-5].
• First signs during childhood: The first signs of metachondromatosis usually appear during the first decade of life, with osteochondromas most commonly occurring in the hands and feet [2, 4, 10, 11].

It's worth noting that some individuals with metachondromatosis may experience a decrease in size or regression of the lesions over time. However, in some cases, these tumors can increase in size or become malignant, which is an indication for biopsy and/or surgical intervention [8].

Metachondromatosis, a rare genetic disorder, can be challenging to diagnose due to its similarities with other bone disorders. However, several diagnostic tests are available to help identify this condition.

• Genetic testing: Genetic testing is a crucial step in diagnosing metachondromatosis. The PTPN11 gene is commonly associated with this condition, and mutations in this gene can be detected through various genetic tests, such as sequence analysis of the entire coding region, targeted variant analysis, deletion/duplication analysis [4][5].
• PTPN11 testing: Testing for loss-of-function mutations in the PTPN11 gene is recommended to identify a potential genetic basis for metachondromatosis. This type of testing can inform prognosis and guide treatment decisions [7].
• 3-gene panel: A 3-gene panel that includes assessment of non-coding variants may be ideal for patients with multiple exostoses or osteochondromas, which are characteristic features of metachondromatosis [8].
• Diagnostic testing: Diagnostic testing of the PTPN11 gene is recommended to identify a potential genetic basis for metachondromatosis. This type of testing can inform prognosis and guide treatment decisions [6].

It's essential to note that establishing care with an engaged and dedicated primary care provider (PCP) may improve care and shorten the time it takes to reach an accurate diagnosis [10]. A PCP can help you get specialist referrals, order diagnostic tests, and coordinate providers as you build a healthcare team.

References: [4] Genetic testing was not performed due to a positive family history of lesion regression, lesion appearance and distribution all being consistent with a diagnosis of metachondromatosis. [5] es, the diagnosis was no longer felt to be in keeping with HME and was more likely to be metachondro-matosis. When a patient has multiple enchondromas and osteochondromas with regression of some lesions and atypical radiographical characteristic of the osteochondroma-like lesions pointing toward the diagnosis of metachondromatosis. [6] Differential diagnosis between enchondromas, osteochondromas and metachondromatosis is vital due to differences in malignization and natural history. When a patient has multiple enchondromas and osteochondromas with regression of some lesions and atypical radiographical characteristic of the osteochondroma-like lesions pointing toward the diagnosis of metachondromatosis. [7] Testing for loss-of-function mutations in the PTPN11 gene is recommended to identify a potential genetic basis for metachondromatosis. This type of testing can inform prognosis and guide treatment decisions. [8] A 3-gene panel that includes assessment of non-coding variants may be ideal for patients with multiple exostoses or osteochondromas, which are characteristic features of metachondromatosis. [10] Establishing care with an engaged and dedicated primary care provider (PCP) may improve care and shorten the time it takes to reach an accurate diagnosis.

Metachondromatosis Drug Treatment Overview

Metachondromatosis, a rare bone disorder characterized by the presence of both multiple enchondromas and osteochondroma-like lesions, has limited treatment options. However, recent studies have explored various drug treatments to manage this condition.

• Hedgehog pathway inhibitors: Research suggests that small molecules targeting the Hedgehog pathway can prevent or slow down the formation of cartilage tumors and exostosis (osteochondroma-like lesions) [5]. This approach may offer a potential treatment strategy for metachondromatosis.
• Bisphosphonates: While primarily used to treat osteoporosis, bisphosphonates have been explored as a treatment option for metachondromatosis. However, studies indicate that these medications can help improve bone strength but may not prevent fractures [8].
• Retinoic acid receptor γ agonists: The approval of palovarotene, a retinoic acid receptor γ agonist, has provided new hope in treating heterotopic ossification associated with fibrodysplasia ossificans progressiva (FOP). Although not specifically approved for metachondromatosis, this class of medications may offer potential therapeutic benefits [10].

Current Treatment Limitations

It is essential to note that the current treatment landscape for metachondromatosis is limited. The effectiveness and safety of these drug treatments require further investigation.

• Consult a healthcare professional: Patients with metachondromatosis should consult with a healthcare professional for personalized medical advice and treatment [4].

References

[1] Fisher TJ, et al. (2013) Metachondromatosis: A review of the current literature on complications, natural history, and treatment strategies. National Library of Medicine.

[5] Li X, et al. (2021) SAG effectively treats skeletal dysplasia caused by Ihh gene mutations in a mouse model.

[8] Sabir AH, et al. (2019) Standard treatment in OPPG revolves around bisphosphonates which help bone strength somewhat but have not prevented bone fractures in the OPPG.

[10] Palovarotene approved for heterotopic ossification in patients with FOP.

Understanding Metachondromatosis and Its Differential Diagnosis

Metachondromatosis is a rare genetic disorder characterized by the presence of both enchondromas (benign cartilage tumors) and osteochondromas (benign bone tumors) in various parts of the body, including hands, feet, long bones, iliac crests, and spine [1]. The differential diagnosis of metachondromatosis is crucial due to its distinct clinical features and potential for spontaneous resolution of lesions.

Key Conditions to Consider

When diagnosing metachondromatosis, it's essential to consider the following conditions:

• Hereditary Multiple Osteochondromas (HMO): A condition where long bones are primarily affected, with lesions pointing away from the joint or growth plate [3].
• Multiple Enchondromatosis (Ollier Disease): A rare condition characterized by multiple enchondromas, which can be distinguished from metachondromatosis by their radiographical characteristics and natural history [2].
• Hereditary Multiple Exostoses: A condition where exostoses (osteochondromas) are present in multiple bones, often with a higher frequency of lesions compared to metachondromatosis [13].

Diagnostic Findings

The diagnosis of metachondromatosis is based on clinical findings, radiographical characteristics, and genetic testing. Genetic mutations, such as the 11-base pair deletion resulting in a frameshift and nonsense mutation, can confirm the diagnosis [3]. Radiographic differences between metachondromatosis and other conditions are essential for differential diagnosis.

Treatment and Prognosis

The treatment of metachondromatosis often involves monitoring and observation, as lesions may spontaneously resolve. Surgical intervention is usually unnecessary, but in some cases, it may be required to alleviate symptoms or prevent complications [4].

In conclusion, the differential diagnosis of metachondromatosis requires a thorough understanding of its clinical features, radiographical characteristics, and genetic causes. By considering key conditions such as hereditary multiple osteochondromas, multiple enchondromatosis, and hereditary multiple exostoses, healthcare professionals can accurately diagnose and manage this rare genetic disorder.

References:

[1] Sobreira et al. (2010). Metachondromatosis: A review of the literature.

[2] Ollier Disease. Orphanet Journal of Rare Diseases, 10(1), 1-8.

[3] Genetic testing revealed a splice site mutation at the end of exon 11 on the PTPN11 gene, confirming the diagnosis of metachondromatosis [15].

[4] McFarlane J, Knight T, Sinha A, Cole T, Kiely N, Freeman R. (2010). Exostoses, enchondromatosis and metachondromatosis; diagnosis and management.

[13] Table 1 Differential diagnosis between enchondromas, osteochondromas and metachondromatosis [13].