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Review
. 2014 Jul;23(3):65-72.
doi: 10.1297/cpe.23.65. Epub 2014 Aug 6.

Skeletal Deformity Associated with SHOX Deficiency

Atsuhito Seki  1 , Tomoko Jinno  2 , Erina Suzuki  2 , Shinichiro Takayama  1 , Tsutomu Ogata  3 , Maki Fukami  2
Affiliations
Review

Skeletal Deformity Associated with SHOX Deficiency

Atsuhito Seki et al. Clin Pediatr Endocrinol. 2014 Jul.

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.

Keywords: Leri-Weill dyschondrosteosis; Madelung deformity; Vickers ligament; chondrocyte; short stature.

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Figures

Fig. 1.
Fig. 1.
Madelung deformity in a female patient with SHOX deficiency. Upper panel: appearance of the forearm. Prominence of the distal ulna is shown. Lower panel: radiographic findings. Shortening and bowing of the radius and dorsal subluxation of the ulnar head are shown.
Fig. 2.
Fig. 2.
Forearm three-dimensional computed tomography of a female patient with SHOX deficiency. Significant findings include shortening of the radius, pyramidal configuration of the carpal bones and dorsal subluxation of the ulna in addition to severely disturbed structural organization of the elbow joint.
Fig. 3.
Fig. 3.
Schematic representation of the Vickers ligament that tethers the lunate to the distal portion of the radius. This ligament seems to consist of hypertrophied connective tissues that form under the mechanical force that arises from asymmetrical growth of the radius and ulna.
See this image and copyright information in PMC

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