Eiken familial skeletal dysplasia

(OMIM phenotype number #600002)

Eiken syndrome is a rare familial skeletal dysplasia, caused by homozygous mutation in the PTH/PTHrP receptor (PTHR1) gene. This disease is characterized by multiple epiphyseal dysplasia, with extremely retarded ossification (principally of the epiphyses, pelvis, hands and feet), as well as by abnormal modeling of the bones in hands and feet, abnormal persistence of cartilage in the pelvis and mild growth retardation. It has been described in a unique consanguineous family and the transmission is autosomal recessive. Eiken familial skeletal dysplasia and Blomstrand chondrodysplasia (see also BOCD) are both caused by recessive mutations in PTHR1, but patients with Eiken syndrome have a severely delayed skeletal maturation. The phenotype in Eiken syndrome is more similar to Jansen chondrodysplasia (see also JMC), although the syndromes clearly differ by the mode of inheritance, specific skeletal features and calcium (Ca) and phosphate (Pi) concentrations.

Gene

PTHR1 gene, 3p21.31 (OMIM gene/locus number #168468). Chondrodysplasias with mineral ion homeostasis are abnormalities due to alterations of the PTHR1 gene, which usually mediates the actions of the two ligands: PTH and PTH-related peptide. PTHR1 activates several signal transduction pathways, including adenyl cyclase (AC)/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC). (see also BOCD)

Phenotype

Multiple epiphyseal dysplasia, severely retarded ossification of epiphyses, pelvis, hands, and feet, abnormal modeling of bones of hands and feet. No mental retardation.

Main biochemical alterations

Normal-high PTH, normal Ca, Pi, and 1,25(OH)2D.

References

  1. Eiken M, Prag J, Petersen KE, et al. A new familial skeletal dysplasia with severely retarded ossification and abnormal modeling of bones especially of the epiphyses, the hands, and feet. Eur J Pediatr. 1984 Feb;141(4):231-5.
  2. Duchatelet S, Ostergaard E, Cortes D, et al. Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes. Hum Mol Genet. 2005 Jan 1;14(1):1-5.
  3. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  4. http://www.omim.org