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Jansen Sign

Exams and Signs

Historical Overview

  • In 1934, Jansen described the first case of a subtype of metaphyseal chondrodysplasia that came to be known as Jansen’s metaphyseal chondrodysplasia (JMC). This skeletal dysplasia is characterized by progressive growth plate abnormalities and sclerosis of some bones that is typically associated with major changes in mineral ion homeostasis.1

Description

  • Jansen sign is a clinical indication of a possible diagnosis of JMC in the presence of short, clubbed fingers concomitant with other features of the disorder.1,2

Pathophysiology

  • JMC, also known as Jansen disease, is an extremely rare autosomal-dominant disease that is primarily characterized by short-limbed stature, typical facies, waddling gait, swelling of the joints, short, clubbed fingers, bowing of the legs, and hypercalcemia that develops postnatally due to delayed chondrocyte differentiation.1-3
  • JMC is caused by heterozygous, activating mutations of the parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR1). So far, five different PTHR1 mutations affecting one of three different amino acid residues have been identified in JMC patients, all of which cause constitutive, ligand-independent receptor activation.1,4
    • Most cases appear to result from de novo mutations, while only a few parent-to-child transmissions of an established disease-causing PTH1R mutation have been reported.1
  • JMC is also typically associated with severe—and generally asymptomatic—hypercalcemia and hypophosphatemia, with low-normal or undetectable serum PTH levels.1
  • Most cases of JMC are diagnosed during childhood, based on a combination of radiographic and biochemical abnormalities, but some patients with less severe disease progression are not diagnosed until adulthood.1
  • Of the three main subtypes of metaphyseal chondrodysplasia, Jansen type is considered to be the most severe. 

Instructions

  1. Obtain a complete and accurate patient history that includes questions related to other clinical indications of JMC.
  2. Perform a careful examination of the patient’s hands.
  3. Look for any signs of shortened and/or clubbed digits.

Related Signs and Tests

  • X-ray
    • The diagnostic radiographic manifestations of JMC include severe metaphyseal dysplasia, large epiphyses, wide distance between the epiphyses and metaphyses in the long bones, and a sclerotic skull base.2
    • These findings are associated with failure of the long bones to grow normally, which results in severely reduced adult height. Sclerosis of the base of the skull is typically recognized by late childhood and is evident in adults but has also been documented during infancy.1
  • Laboratory tests
    • Calcium and phosphorous levels in the blood and urine
  • Differential diagnosis for JMC:
    • Hypochondroplasia
    • McKusick type metaphyseal chondrodysplasia
    • Spahr type metaphyseal chondrodysplasia
    • Schmid type metaphyseal chondrodysplasia
    • Vitamin D deficiency rickets

Diagnostic Performance Characteristics

  • JMC has been found to demonstrate significant clinical and radiographic variability, and the appearance of the disease changes during childhood. However, because of the rarity of this disorder, the range of variability for the patients of the same age is uncertain. At any given age, it may be difficult to determine which patients may have JMC and its variants, and which may have similar but separate entities.2
Definition of Positive Result
  • A positive result occurs when the clinician observes any shortened or clubbed fingers.
Definition of Negative Result
  • A negative result occurs when the clinician does not observe any shortened or clubbed fingers.
Comments and Pearls
  • In infancy, osteopenia, subperiosteal erosions, and hypercalcemia may cause confusion with hyperparathyroidism.2
  • After a positive Jansen sign, additional diagnostic studies are needed; however, in some reports, the diagnosis of JMC is uncertain because of insufficient radiographic documentation.2
References
  1. Nampoothiri, S, Fernandez-Rebollo, E, Yesodharan, D, et al. Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R-PTH1R Mutations With or Without Overt Hypercalcemia. J Clin Endocrinol Metab 2016;101(11):4283-4289. PMID: 27410178
  2. Kozlowski, K, Campbell, JB, Azouz, ME, et al. Metaphyseal chondrodysplasia, type Jansen. Australas Radiol 1999;43(4):544-7. PMID: 10901979
  3. Schipani, E, Kruse, K and Juppner, H. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science1995;268(5207):98-100. PMID: 7701349
  4. Saito, H, Noda, H, Gatault, P, et al. Progression of Mineral Ion Abnormalities in Patients With Jansen Metaphyseal Chondrodysplasia. J Clin Endocrinol Metab 2018;103(7):2660-2669. PMID: 29788189
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