Jansen's metaphyseal chondrodysplasia

Jansen's Metaphyseal Chondrodysplasia (JMC) Overview

Jansen's metaphyseal chondrodysplasia (JMC) is a rare and extremely severe form of skeletal dysplasia, characterized by abnormal endochondral bone formation. This genetic disorder affects the development of bones in the arms and legs, leading to severe short-limbed dwarfism.

Key Features:

• Short-limbed short stature: Individuals with JMC are born with severely shortened limbs, which become more pronounced as they grow.
• Waddling gait: The abnormal bone formation affects the joints, causing a characteristic waddling gait.
• Bowed legs: The legs are often bowed or curved due to the abnormal metaphyseal changes.
• Contracture deformities of the joints: JMC can lead to contractures and deformities in the joints, affecting mobility.
• Short hands with clubbed fingers: Individuals may have short hands with clubbed fingers, a characteristic feature of JMC.
• Clinodactyly: The little finger is often curved or bent due to abnormal bone formation.
• Prominent upper face and small mandible: JMC can cause a prominent upper face and a small jaw (mandible).

Causes and Diagnosis

JMC is caused by constitutively active heterozygous mutations in the parathyroid hormone type 1 receptor gene. This genetic mutation leads to overactivity of the receptor, causing abnormal bone formation.

Diagnosis is typically made through radiological imaging, such as X-rays or CT scans, which reveal characteristic metaphyseal changes and abnormalities in bone development.

Treatment Options

While there are no specific treatments for JMC, management focuses on addressing related complications, such as contractures and joint deformities. Treatment options may include physical therapy, orthotics, and surgical interventions to improve mobility and alleviate symptoms.

Sources: * OMIM (Online Mendelian Inheritance in Man) * Various medical articles and research papers within the provided context.

Physical Characteristics and Symptoms

Jansen's metaphyseal chondrodysplasia (JMC) is a rare genetic disorder that affects the development of bones, particularly in children. The condition is characterized by several distinct physical characteristics and symptoms.

• Short-limbed short stature: Affected individuals exhibit unusually short arms and legs, which become apparent during early childhood [1].
• Waddling gait: Children with JMC often have a waddling gait due to the abnormal development of their bones and joints [3][7].
• Bowed legs: The limbs of affected individuals may show progressive changes, including bowed legs, contracture deformities of the joints, and short stature [5].
• Stunted growth: Patients with JMC often experience stunted growth, which can lead to short-limbed dwarfism [2][4].
• Enlarged joints: The joints of affected individuals may appear enlarged due to the abnormal regulation of chondrocyte growth and differentiation [9].

Early Childhood Diagnosis

Diagnosis typically occurs during infancy or early childhood, based on physical characteristics and symptoms. X-rays may reveal abnormal bone development, which can confirm the diagnosis.

• Age of onset: The condition is first recognized in early childhood, around 2-3 years old, when children present with a waddling gait and other characteristic features [1][7].
• Progressive changes: The limbs of affected individuals typically show progressive changes caused by an abnormal regulation of chondrocyte growth and differentiation [9].

These physical characteristics and symptoms are key indicators of Jansen's metaphyseal chondrodysplasia, a rare genetic disorder that affects bone development in children.

Diagnostic Tests for Jansen's Metaphyseal Chondrodysplasia

Jansen's metaphyseal chondrodysplasia is a rare genetic disorder that affects the development of bones. Diagnosing this condition can be challenging, but several tests can help confirm the diagnosis.

• Laboratory tests: Tests that detect abnormally high levels of calcium in the urine (hypercalciuria) and blood (hypercalcemia) are helpful in confirming the diagnosis [1].
• Clinical evaluation: A thorough clinical evaluation, including identification of characteristic physical findings, is essential for diagnosing Jansen's metaphyseal chondrodysplasia [3].
• Genetic analysis: Genetic analysis can provide a molecular diagnosis of this disorder and is recommended for individuals with a personal and/or family history of this condition [9].

Specialized tests

In addition to the above-mentioned tests, other specialized tests may be used to confirm the diagnosis. These include:

• Radiographic tests: Radiographic tests, such as X-rays or CT scans, can help identify characteristic bone changes associated with Jansen's metaphyseal chondrodysplasia [3].
• Hypercalciuria and hypercalcemia tests: Tests that detect hypercalciuria and hypercalcemia are also helpful in the diagnosis of this condition [7].

No commercially available diagnostic test

It is worth noting that there is no commercially available diagnostic test for Jansen's metaphyseal chondrodysplasia, and diagnosis is often made based on family history associated with typical radiographic and clinical features [5].

References: [1] Context result 1 [3] Context result 3 [7] Context result 7 [9] Context result 9

Current Treatment Options for Jansen's Metaphyseal Chondrodysplasia

Jansen's metaphyseal chondrodysplasia is a rare genetic disorder that affects bone growth and development. While there is no definitive cure, various treatment options are available to manage the symptoms and improve quality of life.

• Symptomatic Treatment: The primary goal of treatment is to alleviate specific symptoms associated with JMC, such as joint abnormalities, hypercalcemia (elevated calcium levels), and bone deformities [4]. Physical therapy and orthopedic surgery may be employed to address these issues.
• Investigational Therapies: Researchers are exploring new investigational drugs, including a PTH Receptor Inverse Agonist (PTH-IA) [3], which has shown promise in treating JMC. These emerging therapies aim to target the underlying causes of the condition.
• Management of Hypercalcemia: Treatment for hypercalcemia may involve medications like alendronate, which can help control calcium levels and prevent complications [7].
• Regular Monitoring: Regular monitoring of growth and development is essential to ensure that any potential issues are addressed promptly.

Current Research Efforts

Researchers are actively working on developing new treatments for JMC. For example:

• A pre-clinical drug development project aims to create a treatment for patients with Jansens Metaphyseal Chondrodysplasia [5].
• Another research project focuses on identifying selective inhibitors of PTH-receptor for Jansen's metaphyseal chondrodysplasia, which began in September 2022 [10].

Support and Awareness

The Jansen's Foundation is dedicated to raising awareness about the condition and supporting research efforts aimed at finding a cure. Their mission is to bring hope to individuals affected by JMC.

References:

[1] NCATS has been working with researchers at Massachusetts General Hospital to develop new treatments for JMC. [2] Treatment of JMC is directed toward specific symptoms apparent in each individual. [3] Development of a PTH Receptor Inverse Agonist (PTH-IA) as a new investigational drug for treatment of patients with JMC. [4] Physical therapy and/or orthopedic surgery may be used to treat particular symptoms of JMC, such as joint abnormalities. [5] A Treatment for Patients with Jansens Metaphyseal Chondrodysplasia ... Type of research project: Pre-clinical drug development / Drug delivery. Status: Ongoing. [6] THE MISSION OF THE JANSEN'S FOUNDATION IS TO BRING AWARENESS AND SUPPORT RESEARCH IN HOPES OF BRINGING ABOUT A CURE TO JANSEN'S METAPHYSEAL CHONDRODYSPLASIA, A [7] Potential Effects of Alendronate on Fibroblast Growth Factor 23 Levels and Effective Control of Hypercalciuria in an Adult with Jansen's Metaphyseal ... [8] Treatment is symptomatic and may include physical therapy, orthopedic interventions, and management of hypercalcemia. Regular monitoring of growth and ... [9] Orphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. [10] The project entitled,

Differential Diagnosis of Jansen's Metaphyseal Chondrodysplasia

Jansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by progressive growth plate abnormalities and sclerosis of some bones. When considering the differential diagnosis for JMC, several other types of metaphyseal chondrodysplasias should be taken into account.

• Hypochondroplasia: This is a rare inherited skeletal disorder that can present with short-limbed dwarfism, similar to JMC [1]. However, hypochondroplasia typically has a milder phenotype and does not involve the same degree of growth plate abnormalities as JMC.
• Schmid metaphyseal chondrodysplasia: This is another rare disorder characterized by moderately short stature with short limbs, coxa vara, bowlegs, and an abnormal gait [6]. While Schmid metaphyseal chondrodysplasia shares some similarities with JMC, it typically does not involve the same level of growth plate abnormalities.
• Pena-Shokeir syndrome: This is a rare genetic disorder that can present with short-limbed dwarfism and severe growth retardation [5]. However, Pena-Shokeir syndrome typically involves additional features such as craniofacial abnormalities and cardiac defects.

Key differences between JMC and other metaphyseal chondrodysplasias

• Growth plate abnormalities: JMC is characterized by progressive growth plate abnormalities, which can lead to short-limbed dwarfism [2]. In contrast, hypochondroplasia typically has a milder phenotype and does not involve the same degree of growth plate abnormalities.
• Sclerosis of bones: JMC is also associated with sclerosis of some bones, particularly in the metaphyses [3]. This feature can help distinguish JMC from other types of metaphyseal chondrodysplasias.

References

[1] ... (context 1) [2] by S Nampoothiri · 2016 · Cited by 28 — Jansen's metaphyseal chondrodysplasia (JMC) (1) is a rare skeletal dysplasia characterized by progressive growth plate abnormalities and sclerosis of some bones ... [3] Sep 18, 2023 — Jansen's metaphyseal chondrodysplasia (JMC) is a rare disorder of the bone with an autosomal dominant pattern of inheritance. [4] by M Dahl · 1996 · Cited by 5 — Other types are Schmid, Spahr, McKusick, Schwachman and Jansen, which can be separated by clinical, radiographic, genetic and biochemical criteria. We ... [5] Jul 21, 2022 — Classification ; Schmid type - mild type, due to mutation in type X collagen (COL10A1 gene), metaphyses are cupped resembling rickets ; Pena and ... [6] Schmid metaphyseal chondrodysplasia is a rare disorder characterized by moderately short stature with short limbs, coxa vara, bowlegs and an abnormal gait. [7] Jun 16, 2021 — Patients present with short-limb dwarfism characterized by genu varum, coxa vara, and spinal abnormalities. Diagnosis is made based on family ... [8] Cause. Jansen's metaphyseal chondrodysplasia is caused by a mutation in the PTH1R gene. Most cases are due to a spontaneous mutation. Inheritance is autosomal ... [9] by H Saito · 2018 · Cited by 24 — Jansen metaphyseal chondrodysplasia is caused by heterozygous activating PTH/PTHrP receptor mutations that lead to mineral ion abnormalities, delayed chond. [10] by H Jüppner · 1996 · Cited by 31 — Jansen's metaphyseal chondrodysplasia (JMC) is a rare genetic disorder that is characterized by short-limbed dwarfism and severe, agonist-independent ...