Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant condition.Shurtleff DB, Sparkes RS, Clawson DK, Guntheroth WG, Mottet NK (1964) Hereditary osteolysis with hypertension and nephropathy. JAMA 188:363–368 Also known as idiopathic multicentric osteolysis with nephropathy, it is characterized by progressive destruction of the carpal and tarsal bones and renal failure.

Signs and symptoms

The condition presents with gradual loss of the small bones in the carpus and tarsus, which may lead to joint subluxation and instability. Renal failure, when present, typically manifests as proteinuria.

In some cases, there may also be craniofacial abnormalities including Triangular facies Micrognathia Maxillary hypoplasia Exophthalmos

Histological examination of renal biopsies shows glomerulosclerosis and severe tubulointerstitial fibrosis. Intellectual disability may also occur.

Genetics

This condition is caused by mutations in the transcription factor MafB, or V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), gene.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 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.

Classification

This condition has been classified into five types.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 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

Differential diagnosis The condition should be differentially diagnosed from juvenile rheumatoid arthritis and other genetic skeletal dysplasias as Multicentric Osteolysis, Nodulosis, and Arthropathy.

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.

References