Metaphyseal Chondrodysplasia, Jansen Type

Extremely rare progressive disorder in which portions of the bones of the arms and legs develop abnormally with unusual cartilage formations and subsequent abnormal bulbous metaphyses (metaphyseal chondrodysplasia). Affected individuals exhibit unusually short arms and legs and short stature (short-limbed dwarfism), findings that typically become apparent during early childhood. Infants with Jansen-type metaphyseal chondrodysplasia may have characteristic facial abnormalities and additional skeletal malformations. Hypercalcemia is present.

Jansen Metaphyseal Dysplasia; Murk Jansen Metaphyseal Chondrodysplasia; Chondrodysplasia Jansen type

Fewer than 25 cases have been reported in the literature.

Autosomal dominant. Majority of cases are sporadic.

Caused by mutation in parathyroid hormone receptor 1 gene (PTHR1), which has been mapped to 3p22-p21.1.

Clinically evocated by the postnatal onset of severe short stature with joint dysfunction. Radiologic signs vary with age, showing diffuse radiolucency at birth, irregular calcification in childhood, and bulbous deformations of long bone extremities.

Severe short stature (adult height: 125 cm [49.2 inches]) and enlarged joints with flexion contractures (knees, hips). Small thorax, kyphoscoliosis. Irregular and disorganized metaphyses but normal epiphyses. Small face with prominent supraorbital ridges; micrognathia; sometimes choanal atresia, high-arched palate, mandibular cyst. Wide cranial sutures with hyperostosis of calvaria and cranial bone sclerosis. Variable deafness. Waddling gait. Biochemistry: Hypercalcemia, hypercalciuria, hypophosphatemia. Increased urinary cAMP; elevated 1,25(OH2D3 , alkaline phosphatase; low/absent parathyroid hormone.

Assess renal function and serum calcium and phosphate levels. Hypercalcemia may be asymptomatic or may be associated with polyuria, dehydration, thrombosis, muscle weakness, and hyporeflexia. ECG is recommended. In the presence of symptomatic or clinically significant hypercalcemia, active steps should be taken to lower the serum levels (i.e., with saline rehydration/diuresis). Phosphate supplementation may be required. Evaluate carefully the airway for potential difficult tracheal intubation (clinical, radiograph). Evaluate severity of the disease (clinical, full history, radiographs).

Anesthesia in this condition has not been described. The features of the disease suggest that face-mask ventilation, direct laryngoscopy, and tracheal intubation may be difficult. If it is the case, spontaneous respiration should be maintained until confirmation that face-mask ventilation can support gas-exchange or until the trachea has been secured and lung ventilation confirmed. Renal dysfunction may be present. Patient positioning may be difficult because of contractures. Patients may be prone to fractures. Hypercalcemia may lead to arrhythmias and hypertension. Hyperventilation may be useful in life-threatening hypercalcemia. Neuromuscular monitoring is recommended to facilitate titration of muscle relaxants.

Metabolism/excretion of some drugs may be altered in the presence of renal dysfunction. Digitalis toxicity is exacerbated by hypercalcemia. The response to neuromuscular blockers may be potentialized by hypercalcemia. Consider renal function before using aminoside antibiotics.