Multicentric carpotarsal osteolysis syndrome

Multicentric carpotarsal osteolysis syndrome is a rare autosomal dominant condition.[2] This condition is also known as idiopathic multicentric osteolysis with nephropathy. It is characterised by carpal-tarsal destruction and kidney failure.

Multicentric carpotarsal osteolysis syndrome
Other namesMCTO[1]
This condition is inherited in an autosomal dominant manner.
SpecialtyMedical genetics

Signs and symptoms

The presentation is of gradual loss of the small bones in the carpus and tarsus. This may lead to joint subluxation and instability.

The kidney failure, when present, usually presents as the presence of protein in the urine.

In some cases, there may also be craniofacial abnormalities including

Histology of renal biopsies show glomerulosclerosis and severe tubulointerstitial fibrosis.

Intellectual disability may occur.

Genetics

This condition is caused by mutations in the transcription factor MafB, or V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), gene.[3] This gene encodes a basic leucine zipper (bZIP) transcription factor.

The gene is located on the long arm of chromosome 20 (20q11.2-q13.1).

Pathogenesis

How this mutation causes the clinical picture is not currently clear.

Diagnosis

The diagnosis may be suspected on the basis of the constellation of clinical features. It is made by sequencing the MAFB gene.

Differential diagnosis

The condition should be differentially diagnosed from juvenile rheumatoid arthritis.

Classification

This condition has been classified into five types.[4]

  • Type 1: hereditary multicentric osteolysis with dominant transmission
  • Type 2: hereditary multicentric osteolysis with recessive transmission
  • Type 3: nonhereditary multicentric osteolysis with nephropathy
  • Type 4: Gorham–Stout syndrome
  • Type 5: Winchester syndrome – defined as a monocentric disease with autosomal recessive inheritance

Treatment

Optimal treatment for this condition is unclear. Bisphosphonates and denosumab may be of use for the bone lesions. Cyclosporine A may be of use for treating the nephropathy. Steroids and other immunosuppressant drugs do not seem to be of help.

History

This condition was first described by Shurtleff et al. in 1964.[2]

gollark: Loading self-replicator beeoids... makes it unusably slow, great.
gollark: And... apiomemetics makes everything do somewhat better, how nice of it.
gollark: I'll load in apiomemetics.
gollark: Mine consistently does about 3000 better over 50 metarounds.
gollark: ```(angel -97392)(tit-for-tat -83669)(devil -85670)(time-machine -78224)(tat-for-tit -112052)(grudger -68152)(random-choice -104122)(apl -97870)(angry-tit-for-tat -92851)(forgiving-grudge -66681)(meapiometics -79127)```

References
  1. "OMIM Entry - # 166300 - MULTICENTRIC CARPOTARSAL OSTEOLYSIS SYNDROME; MCTO". omim.org. Retrieved 27 April 2019.
  2. Shurtleff DB, Sparkes RS, Clawson DK, Guntheroth WG, Mottet NK (1964) Hereditary osteolysis with hypertension and nephropathy. JAMA 188:363–368
  3. Zankl A, Duncan EL, Leo PJ, Clark GR, Glazov EA, Addor M-C, Herlin T, Kim CA, Leheup BP, McGill J, McTaggart S, Mittas S, Mitchell, AL, Mortier GR, Robertson SP, Schroeder M, Terhal P, Brown MA (2012) Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB. Am J Hum Genet 90: 494-501
  4. Hardegger F, Simpson LA, Segmueller G (1985) The syndrome of idiopathic osteolysis. Classification, review, and case report. J Bone Joint Surg Br 67(1):88-93
Classification
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