Jansen's metaphyseal chondrodysplasia

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).

Jansen's metaphyseal chondrodysplasia
Other namesMurk Jansen-type metaphyseal chondrodysplasia, Jansen metaphyseal dysostosis, Jansen disease
Jansen's metaphyseal chondrodysplasia is inherited in an autosomal dominant manner.

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).[1]

Presentation

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 interstitum of the kidney) is seen commonly as well.

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.[2]

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.[2]

Treatment

There is no known treatment at present, although some investigators have tried to lessen the hypercalcemia with various forms of bisphosphonates.

Eponym

It is named for Murk Jansen (1867–1935), a Dutch orthopedic surgeon.[3][4]

References
  1. 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.
  2. "Jansen Type Metaphyseal Chondrodysplasia - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2018-03-16.
  3. 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.
  4. 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
Classification
External resources
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