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

ligand In coordination chemistry, a ligand is an ion or molecule with a 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 el ...

-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 & Genetics

Blood levels of

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates serum calcium and phosphate through its actions on the bone, kidneys, and small intestine. PTH incre ...

(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 (physical form and structure), its developmental processes, its biochemical and physiological propert ...

, or short stature. Examination of the bone reveals normal

epiphyseal plate The epiphyseal plate, 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, with ma ...

s but disorganized

metaphyseal The metaphysis (: metaphyses) 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 epip ...

regions.

Hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium 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 def ...

(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 soft ...

(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 (: choana), posterior nasal apertures or internal nostrils are two openings found at the back of the nasal passage between the nasal cavity and the pharynx, in humans and other mammals (as well as crocodilians and most skinks). They ...

stenosis Stenosis () is the abnormal narrowing of 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'' as a term is usually used when narrowing ...

, wide

cranial sutures In anatomy, fibrous joints are joints connected by Fibrous connective tissue, 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 ...

and irregular formation of the long bones which can resemble

rickets Rickets, scientific nomenclature: rachitis (from Greek , meaning 'in or of the spine'), is a condition that results in weak or soft bones in children and may have either dietary deficiency or genetic causes. Symptoms include bowed legs, stun ...

. 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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

Diagnosis

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

X-rays An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

may reveal abnormal development of the bulbous ends of the

metaphyses The metaphysis (: metaphyses) 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 epip ...

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 excrete higher levels ...

and

hypercalcaemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium 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 defin ...

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 to treat osteoporosis. Evidence shows that they reduce the risk of fracture in p ...

. 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.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 Rare syndromes Growth disorders Cell surface receptor deficiencies