title: Skeletal Deformity Associated with SHOX Deficiency.
abstract: SHOX haploinsufficiency due to mutations in the coding exons or microdeletions involving the coding exons and/or the enhancer regions accounts for approximately 80% and 2-16% of genetic causes of Leri-Weill dyschondrosteosis and idiopathic short stature, respectively. The most characteristic feature in patients with SHOX deficiency is Madelung deformity, a cluster of anatomical changes in the wrist that can be attributed to premature epiphyseal fusion of the distal radius. Computed tomography of SHOX-deficient patients revealed a thin bone cortex and an enlarged total bone area at the diaphysis of the radius, while histopathological analyses showed a disrupted columnar arrangement of chondrocytes and an expanded hypertrophic layer of the growth plate. Recent studies have suggested that perturbed programmed cell death of hypertrophic chondrocytes may underlie the skeletal changes related to SHOX deficiency. Furthermore, the formation of an aberrant ligament tethering the lunate and radius has been implicated in the development of Madelung deformity. Blood estrogen levels and mutation types have been proposed as phenotypic determinants of SHOX deficiency, although other unknown factors may also affect clinical severity of this entity.
authors.affiliation: Department of Orthopedic Surgery, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Seki
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Jinno
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Department of Orthopedic Surgery, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takayama
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
keywords: Leri-Weill dyschondrosteosis; Madelung deformity; Vickers ligament; chondrocyte; short stature
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