Jansen's metaphyseal chondrodysplasia


Jansen's metaphyseal chondrodysplasia is a disease that results from ligand-independent activation of the type 1 of the parathyroid hormone receptor, due to one of three reported mutations.
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, and from a mother to her 2 sons.

Presentation

Blood levels of parathyroid hormone 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 and hypophosphatemia, 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 jaw, choanal stenosis, wide cranial sutures and irregular formation of the long bones which can resemble rickets. Nephrocalcinosis 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.

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.

Eponym

It is named for Murk Jansen, a Dutch orthopedic surgeon.