Jansen's metaphyseal chondrodysplasia

Presentation & Genetics

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. 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.

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

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.

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 dominant.

Diagnosis

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.

Treatment

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.

Eponym

It is named for Murk Jansen (1867–1935), a Dutch orthopedic surgeon.

References

References

1. (September 1993). "Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes.". Journal of Clinical Investigation.
2. (20 August 2019). "Nebraska's Neena Nizar Seeks Cure for Jansen's, One of World's Rarest Diseases".
3. (1996-09-05). "Constitutively Activated Receptors for Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Jansen's Metaphyseal Chondrodysplasia". New England Journal of Medicine.
4. 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.
5. "Jansen Type Metaphyseal Chondrodysplasia - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders).
6. 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.
7. Weber, Matthias M.. (2002). "Effects of Growth Hormone on Skeletal Muscle". Hormone Research in Paediatrics.
8. 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.
9. (1987). "Murk Jansen's metaphyseal chondrodysplasia with long-term followup". Pediatric Radiology.