Jansen's metaphyseal chondrodysplasia
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| Jansen's metaphyseal chondrodysplasia | |
|---|---|
| Other names | Murk Jansen-type metaphyseal chondrodysplasia, Jansen metaphyseal dysostosis, Jansen disease |
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| Jansen's metaphyseal chondrodysplasia is inherited in an autosomal dominant manner. | |
Jansen's metaphyseal chondrodysplasia (JMC) is a disease that results from ligand-independent activation of the type 1 (PTH1R) of the parathyroid hormone receptor, due to one of three reported mutations (activating mutation).[1]
JMC is extremely rare, and as of 2007 there are fewer than 20 reported cases worldwide. There are only 2 known families, from Dubai and Texas, in which the disease was passed from mother to daughter (Texas), and from a mother to her 2 sons (Dubai).[2]
Presentation & Genetics
[edit]Blood levels of parathyroid hormone (PTH) are undetectable, but the mutation in the PTH1R leads to auto-activation of the signaling as though the hormone PTH is present. Severe JMC produces a dwarfing phenotype, or short stature. Examination of the bone reveals normal epiphyseal plates but disorganized metaphyseal regions.[3] Hypercalcemia (elevated levels of calcium in the blood) and hypophosphatemia (reduced blood levels of phosphate), and elevated urinary calcium and phosphate, are generally found in JMC. The absence of hypercalcemia does not eliminate the disease from consideration.[3]
Physical irregularities often associated with Jansen's include: prominent or protruding eyes, a high-arched palate, micrognathia or abnormal smallness of the jaws – particularly the lower (mandible) jaw, choanal stenosis, wide cranial sutures and irregular formation of the long bones which can resemble rickets. Nephrocalcinosis (accumulation of calcium in the renal interstitium) is seen commonly as well.
Clinical features
[edit]Individuals with JMC typically present with short stature, bowed legs, and widened growth plates. Other features may include hypercalcemia, joint pain, and muscle weakness. The severity of symptoms can vary widely among affected individuals.[4]
Cause
[edit]Jansen's metaphyseal chondrodysplasia is caused by a mutation in the PTH1R gene. Most cases are due to a spontaneous mutation. Inheritance is autosomal dominant.[5]
Diagnosis
[edit]Diagnosis typically occurs during infancy or early childhood and is based around physical characteristics and symptoms. X-rays may reveal abnormal development of the bulbous ends of the metaphyses of the limb bones. Tests that detect hypercalciuria and hypercalcaemia are also helpful in the diagnosis.[5][6]
Treatment
[edit]There is no known treatment at present, although some investigators have tried to lessen the hypercalcemia with various forms of bisphosphonates. Treatment is symptomatic and may include physical therapy, orthopedic interventions, and management of hypercalcemia. Regular monitoring of growth and skeletal development is essential for managing the condition.[7]
Eponym
[edit]It is named for Murk Jansen (1867–1935), a Dutch orthopedic surgeon.[8][9]
References
[edit]- ^ Yasuda, H; Mine, T; Shibata, H; Eto, Y; Hasegawa, Y; Takeuchi, T; Asano, S; Kojima, I (September 1993). "Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes". Journal of Clinical Investigation. 92 (3): 1491–1496. doi:10.1172/JCI116727. ISSN 0021-9738. PMC 288295. PMID 8376601.
- ^ Luxner, Larry (20 August 2019). "Nebraska's Neena Nizar Seeks Cure for Jansen's, One of World's Rarest Diseases". Huntington Disease News. Retrieved 16 December 2020.
- ^ a b Schipani, E.; Langman, C.B.; Parfitt, A.M.; Jensen, G.S.; Kikuchi, S.; Kooh, S.W.; Cole, W.G.; Jüppner, H. (1996-09-05). "Constitutively Activated Receptors for Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Jansen's Metaphyseal Chondrodysplasia". New England Journal of Medicine. 335 (10): 708–714. doi:10.1056/nejm199609053351004. ISSN 0028-4793.
- ^ Szabo, E. (2002-08-01). "Loss of Heterozygosity in Parathyroid Glands of Familial Hypercalcemia with Hypercalciuria and Point Mutation in Calcium Receptor". Journal of Clinical Endocrinology & Metabolism. 87 (8): 3961–3965. doi:10.1210/jc.87.8.3961. ISSN 0021-972X.
- ^ a b "Jansen Type Metaphyseal Chondrodysplasia - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2018-03-16.
- ^ Joun, H. (1997-04-01). "Tissue-Specific Transcription Start Sites and Alternative Splicing of the Parathyroid Hormone (PTH)/PTH-Related Peptide (PTHrP) Receptor Gene: A New PTH/PTHrP Receptor Splice Variant that Lacks the Signal Peptide". Endocrinology. 138 (4): 1742–1749. doi:10.1210/en.138.4.1742. ISSN 0013-7227. PMID 9075739.
- ^ Weber, Matthias M. (2002). "Effects of Growth Hormone on Skeletal Muscle". Hormone Research in Paediatrics. 58 (Suppl. 3): 43–48. doi:10.1159/000066482. ISSN 1663-2818.
- ^ Jansen, M. Ueber atypische Chondrodystrophie (Achondroplasie) und ueber eine noch nicht beschriebene angeborene Wachstumsstoerung des Knochensystems: Metaphysaere Dysostosis. Z. Orthop. Chir. 61: 253-286, 1934.
- ^ Silverthorn KG, Houston CS, Duncan BP (1987). "Murk Jansen's metaphyseal chondrodysplasia with long-term followup". Pediatric Radiology. 17 (2): 119–123. doi:10.1007/BF02388087. PMID 3562109. S2CID 23466423.
Further reading
[edit]- Metaphyseal chondrodysplasia, Jansen type -- OrphaNet Information (PDF) Archived 2022-05-03 at the Wayback Machine
- Jansen’s Metaphyseal Chondrodysplasia, Case Report, Indian Pediatrics
- Jansen Type Metaphyseal Chondrodysplasia -- National Organization for Rare Disorders (NORD)
- A Novel Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Mutation in Jansen’s Metaphyseal Chondrodysplasia, The Journal of Clinical Endocrinology & Metabolism (1) Archived 2011-05-16 at the Wayback Machine
- A Form of Jansen’s Metaphyseal Chondrodysplasia with Limited Metabolic and Skeletal Abnormalities Is Caused by a Novel Activating Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Mutation, The Journal of Clinical Endocrinology & Metabolism (2) Archived 2011-05-16 at the Wayback Machine
- Constitutively Activated Receptors for Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Jansen's Metaphyseal Chondrodysplasia, The New England Journal of Medicine[permanent dead link]
- Constitutive Activation of the Cyclic Adenosine 3',5'-Monophosphate Signaling Pathway by Parathyroid Hormone (PTH)/PTH-Related Peptide Receptors Mutated at the Two Loci for Jansen’s Metaphyseal Chondrodysplasia, Molecular Endocrinology Archived 2008-08-29 at the Wayback Machine