Jansen type metaphyseal chondrodysplasia

Alternate names

Metaphyseal chondrodysplasia Murk Jansen type; Murk Jansen type metaphyseal chondrodysplasia

Definition

Jansen's metaphyseal chondrodysplasia (JMC) is a very rare autosomal dominant skeletal dysplasia characterized by short-limbed short stature (due to severe metaphyseal changes that are often discovered in childhood by imaging), waddling gait, bowed legs, contracture deformities of the joints, short hands with clubbed fingers, clinodactyly, prominent upper face and small mandible, as well as chronic parathyroid hormone-independent hypercalcemia, hypercalciuria, and mild hypophosphatemia.

Cause

Five different heterozygous activating PTH/PTHrP receptor (PTH1R) mutations that change one of three different amino acid residues are known to cause JMC.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

It is found to be inherited in autosomal dominant manner.

Clinical presentation

• Jansen's metaphyseal chondrodysplasia (JMC) is a rare skeletal dysplasia characterized by abnormal endochondral bone formation and typically severe hypercalcemia despite normal/low levels of PTH.
• The limbs of affected individuals typically show progressive postnatal changes that are caused by an abnormal regulation of chondrocyte growth and differentiation, eventually leading to short and bowed legs.
• JMC is typically associated with severe and, generally, asymptomatic hypercalcemia and hypophosphatemia, with low-normal or undetectable serum PTH levels.

Diagnosis

• Sclerosis of the skull base, an unusual finding in other skeletal dysplasias along with rickets-like metaphyseal changes, helped establish the diagnosis during infancy.
• However, the H223R mutation did not cause overt hypercalcemia in the affected mother and has been a confounding factor in establishing the diagnosis.

Treatment

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

NIH genetic and rare disease info

• NIH info on Jansen type metaphyseal chondrodysplasia

Jansen type metaphyseal chondrodysplasia is a rare disease.

Jansen type metaphyseal chondrodysplasia Resources
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