Jansen's metaphyseal chondrodysplasia (JMC) is a disease that results from

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elect ...

-independent activation of the type 1 ( PTH1R) of the parathyroid hormone receptor, due to one of three reported mutations (activating mutation). 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).

Presentation

Blood levels of

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. PTH influences bone ...

(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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (biology), morphology or physical form and structure, its Developmental biology, developmental proc ...

, or short stature. Examination of the bone reveals normal

epiphyseal plate The epiphyseal plate (or epiphysial plate, physis, or growth plate) is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place; that is, the whole bone is alive, wit ...

s but disorganized

metaphyseal The metaphysis is the neck portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, and as it grows it ossifies near the diaphysis and the epiphyses. The metap ...

regions.

Hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...

(elevated levels of calcium in the blood) and

hypophosphatemia Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softening ...

(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,

choana The choanae (singular choana), posterior nasal apertures or internal nostrils are two openings found at the back of the nasal passage between the nasal cavity and the throat in tetrapods, including humans and other mammals (as well as crocodili ...

stenosis A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture). ''Stricture'' ...

, wide

cranial sutures In anatomy, fibrous joints are joints connected by fibrous tissue, consisting mainly of collagen. These are fixed joints where bones are united by a layer of white fibrous tissue of varying thickness. In the skull the joints between the bones ar ...

and irregular formation of the long bones which can resemble

rickets Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications ma ...

. Nephrocalcinosis (accumulation of calcium in the renal interstitium) 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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

Diagnosis

Diagnosis typically occurs during infancy or early childhood and is based around physical characteristics and symptoms.

X-rays An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nbs ...

may reveal abnormal development of the bulbous ends of the metaphyses of the limb bones. Tests that detect

hypercalciuria Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that put out higher levels o ...

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 Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...

Eponym

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

References

External links

{{DEFAULTSORT:Jansen's Metaphyseal Chondrodysplasia Syndromes Growth disorders Cell surface receptor deficiencies Rare diseases