Jansen's metaphyseal chondrodysplasia

(Redirected from Jansen's metaphyseal chondroplasia) Rare genetic disorder involving dwarfism and endocrine symptoms

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Medical condition

Jansen's metaphyseal chondrodysplasia
Other names	Murk Jansen-type metaphyseal chondrodysplasia, Jansen metaphyseal dysostosis, Jansen disease

Jansen's metaphyseal chondrodysplasia is inherited in an autosomal dominant manner.

Jansen's metaphyseal chondrodysplasia (JMC) is a disease that results from ligand-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 (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, or short stature. Examination of the bone reveals normal epiphyseal plates but disorganized metaphyseal regions. Hypercalcemia (elevated levels of calcium in the blood) and hypophosphatemia (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, choanal stenosis, wide cranial sutures and irregular formation of the long bones which can resemble rickets. 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.

Diagnosis

Diagnosis typically occurs during infancy or early childhood and is based around physical characteristics and symptoms. X-rays may reveal abnormal development of the bulbous ends of the metaphyses of the limb bones. Tests that detect hypercalciuria 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. 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.

References

Yasuda, H; Mine, T; Shibata, H; Eto, Y; Hasegawa, Y; Takeuchi, T; Asano, S; Kojima, I (September 1993). "Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes". Journal of Clinical Investigation. 92 (3): 1491–1496. doi:10.1172/JCI116727. ISSN 0021-9738. PMC 288295. PMID 8376601.
Luxner, Larry (20 August 2019). "Nebraska's Neena Nizar Seeks Cure for Jansen's, One of World's Rarest Diseases". Huntington Disease News. Retrieved 16 December 2020.
^ Schipani, E.; Langman, C.B.; Parfitt, A.M.; Jensen, G.S.; Kikuchi, S.; Kooh, S.W.; Cole, W.G.; Jüppner, H. (1996-09-05). "Constitutively Activated Receptors for Parathyroid Hormone and Parathyroid Hormone–Related Peptide in Jansen's Metaphyseal Chondrodysplasia". New England Journal of Medicine. 335 (10): 708–714. doi:10.1056/nejm199609053351004. ISSN 0028-4793.
Szabo, E. (2002-08-01). "Loss of Heterozygosity in Parathyroid Glands of Familial Hypercalcemia with Hypercalciuria and Point Mutation in Calcium Receptor". Journal of Clinical Endocrinology & Metabolism. 87 (8): 3961–3965. doi:10.1210/jc.87.8.3961. ISSN 0021-972X.
^ "Jansen Type Metaphyseal Chondrodysplasia - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2018-03-16.
Joun, H. (1997-04-01). "Tissue-Specific Transcription Start Sites and Alternative Splicing of the Parathyroid Hormone (PTH)/PTH-Related Peptide (PTHrP) Receptor Gene: A New PTH/PTHrP Receptor Splice Variant that Lacks the Signal Peptide". Endocrinology. 138 (4): 1742–1749. doi:10.1210/en.138.4.1742. ISSN 0013-7227. PMID 9075739.
Weber, Matthias M. (2002). "Effects of Growth Hormone on Skeletal Muscle". Hormone Research in Paediatrics. 58 (Suppl. 3): 43–48. doi:10.1159/000066482. ISSN 1663-2818.
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.
Silverthorn KG, Houston CS, Duncan BP (1987). "Murk Jansen's metaphyseal chondrodysplasia with long-term followup". Pediatric Radiology. 17 (2): 119–123. doi:10.1007/BF02388087. PMID 3562109. S2CID 23466423.

External links

Classification	D ICD-9-CM: 756.9 OMIM: 156400 MeSH: C537564 DiseasesDB: 31669
External resources	Orphanet: 33067

Osteochondrodysplasias

Osteodysplasia/
osteodystrophy

Diaphysis	Camurati–Engelmann disease
Metaphysis	Metaphyseal dysplasia Jansen's metaphyseal chondrodysplasia Schmid metaphyseal chondrodysplasia
Epiphysis	Spondyloepiphyseal dysplasia congenita Multiple epiphyseal dysplasia Otospondylomegaepiphyseal dysplasia
Osteosclerosis	Raine syndrome Osteopoikilosis Osteopetrosis
Other/ungrouped	FLNB Boomerang dysplasia Opsismodysplasia Polyostotic fibrous dysplasia McCune–Albright syndrome

Chondrodysplasia/
chondrodystrophy
(including dwarfism)

Osteochondroma

osteochondromatosis
- Hereditary multiple exostoses

Chondroma/enchondroma

enchondromatosis
- Ollier disease
- Maffucci syndrome

Growth factor receptor

FGFR2:	Antley–Bixler syndrome
FGFR3:	Achondroplasia Hypochondroplasia Thanatophoric dysplasia

COL2A1 collagen disease

SLC26A2 sulfation defect

Chondrodysplasia punctata

Other dwarfism

Cell surface receptor deficiencies

G protein-coupled receptor
(including hormone)

Class A	TSHR (Congenital hypothyroidism 1) LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty) FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis) GnRHR (Gonadotropin-releasing hormone insensitivity) EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2) AVPR2 (Nephrogenic diabetes insipidus 1) PTGER2 (Aspirin-exacerbated respiratory disease)
Class B	PTH1R (Jansen's metaphyseal chondrodysplasia)
Class C	CASR (Familial hypocalciuric hypercalcemia)
Class F	FZD4 (Familial exudative vitreoretinopathy 1)