Jansen Disease - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Jansen disease was named after a French orthopedic surgeon Murk Jansen. It is an extremely rare disorder, with only twenty cases reported so far in the literature. The literature shows that two families have shown the autosomal dominant inheritance pattern where the disease has passed from mother to daughter in a family in Texas and from mother to her two sons in a family in Dubai. Studies suggest that of the twenty cases reported so far. It does not show any gender predilection; it affects both males and females equally. The severity of the disease varies from person to person.

What Is Jansen Disease?

Jansen disease can be defined as an extremely rare autosomal dominant disorder characterized by skeletal dysplasia due to abnormal cartilage formation. The persons affected by this condition would exhibit a characteristic appearance of short-limbed short stature, deformities of the joint, etc.

What Are the Other Terminologies Used to Denote Jansen Disease?

The other terminologies that are used to indicate this condition include:

• Murk Jansen type metaphyseal chondrodysplasia.

• Jansen metaphyseal dysostosis.

What Is the Etiology of Jansen Disease?

The heterozygous genetic mutation of the gene is located in the short arm of chromosomes 3p21.1 to 3p22 and is found to be responsible for the occurrence of Jansen disease. This chromosome is found in the nucleus of all body cells. This gene codes for a specific protein called the PTH or PTH1R (parathyroid hormone receptor), which regulates the calcium level in the blood. The disease is reported to be inherited as an autosomal dominant pattern. Studies have shown that the majority of cases of Jansen disease show new mutations which occur spontaneously in the developing fetus.

What Is Autosomal Dominant Inheritance Pattern?

The autosomal dominant inheritance pattern occurs when only a single copy of a mutated gene is present in any one of the parents or as a result of a new mutation in the affected individual. The chance of transmitting the disease from one generation to another in each pregnancy is 50%.

What Is the Pathophysiology of Jansen Disease?

• Parathyroid hormone receptors belong to the G-protein-coupled transmembrane receptor family. It activates the adenine cyclase and phospholipase C, thereby regulating the calcium ion of homeostasis in the body. These receptors are highly expressed in the bones and kidneys.

• The suggested pathogenesis of Jansen disease is that the mutation in the gene coding for the parathyroid hormone receptor would result in ligand-independent activation of the parathyroid hormone receptors. This, in turn, results in the autoactivation of the parathyroid hormone receptors in the blood without detectable parathyroid hormone in the blood. Due to this phenomenon, the calcium levels in the blood increase. This increased calcium would start getting deposited in the premature bones. These bones lack proper cartilage as the mineralization of the bone has occurred earlier than its time, thereby resulting in the symptoms of the disorder.

• The affected bones would reveal normal epiphyseal plates but a disorganized metaphyseal region.

What Are the Signs And Symptoms of Jansen Disease?

The signs and symptoms of the condition are as follows:

• Short stature.

• Short limbs.

• Waddling gait (side-to-side way of walking due to weakness of muscles in the pelvic girdle).

• Deformities of the joint.

• Squatting stance (knees and hips are in a bent position, with the feet bearing the body’s weight).

• Contractures of the joint.

• Bowed legs.

• Clubbed fingers.

• Clinodactyly (one finger curved in another direction).

• Prominent upper face.

• High-arched palate.

• Small mandible.

• Protruding eyes.

• Choanal stenosis (narrowing of the back part of the nasal cavity that results in breathing difficulty. It is present during birth-congenital).

• Wide cranial sutures.

What Are the Laboratory Findings of Jansen Disease?

• Hypercalcemia - Increased serum calcium levels.

• Parathyroid Hormone Receptors - Increased serum PTHR1 receptors.

• Hypophosphatemia - Decreased serum phosphate levels.

• Hypercalciuria - Increased urinary excretion of calcium.

How Is Jansen Disease Diagnosed?

• History: A thorough history from the patient, as well as the family members, would provide a major clue in identifying the genetic link in families.

• Physical Examination: A complete physical examination of the patient would reveal the above-discussed features, such as short stature, short limbs, waddling gait, bowed legs, marked facial features, etc.

• X-Ray: X-rays of the arms and limbs would reveal abnormal development of the metaphyseal ends of the bones.

• Blood Test:

• Serum Calcium Levels - Increased serum calcium levels.

• Serum Phosphate levels -Decreased serum phosphate levels.

• Serum Parathyroid Hormone Receptor Levels - Increased serum PTHR1 receptors.

• Urine Test - Elevated calcium levels.

• Hypercalciuria - Increased urinary excretion of calcium.

• Genetic Studies: This would help in identifying the mutations in the respective genes and establishing the definitive diagnosis for the condition.

What Are the Differential Diagnoses of Jansen Disease?

Other conditions which exhibit symptoms similar to that of Jansen disease include:

• Hypochondroplasia - This is a rare skeletal disorder caused due to inadequate or abnormal cartilage formation resulting in short arms, legs, and short stature.

• McKusick Type Metaphyseal Chondrodysplasia - This is also known as cartilage-hair hypoplasia. It is a rare inherited condition characterized by unevenly short arms, increased joint mobility, and fine silky hair.

• Schmid Type Metaphyseal Chondrodysplasia - It is a rare inherited condition characterized by abnormally short arms and legs. It also shows bowed legs and the flaring of bones in the lower rib cage.

• Spahr-Type Metaphyseal Chondrodysplasia -This is a rare disorder characterized by abnormal cartilage and bone formation.

• Vitamin D Deficiency - It is characterized by skeletal deformities as a result of vitamin D deficiency.

How Is Jansen Disease Treated?

• There is no specific treatment for this disorder. The management of the condition is aimed at treating the symptoms. Management may need the coordinated efforts of orthopedic surgeons, pediatricians, dentists, speech therapists, audiologists, and physiotherapists.

• Bisphosphonates are given to reduce hypercalcemia.

• Genetic counseling is recommended for the affected individuals and their family members.

• Other supportive and symptomatic treatments are advised for affected individuals.

Conclusion:

Jansen disease is a very rare skeletal anomaly caused due to abnormal cartilage formation. Only twenty cases are reported in the literature to date, with only two families showing autosomal dominant inheritance patterns. Though it is an extremely rare disorder, the deformities caused as a result of this are severe and permanent. Studies are going on to identify the genetic markers as well as the medications to target the affected genes. This would definitely contribute to controlling the receptor activity of the parathyroid hormone and promoting normal bone growth and development.