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If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Bent or bowed limbs occur in other skeletal malformation syndromes and are not pathognomonic for CD. Major diagnostic radiologic features include bowed or angulated femora and tibiae, hypoplastic scapulae, vertically narrow iliac wings, and nonmineralized thoracic pedicles.

No single feature is diagnostic, but each of these appears with high frequency, and no other syndrome has this combination of features. Additional common radiologic features are facial hypoplasia, abnormal cervical vertebrae, slender ribs, 11 pairs of ribs, small chest, dislocated hips, a variety of pelvic abnormalities, and short first metacarpal. Common clinical features include micrognathia, respiratory distress, flat nasal bridge, pretibial dimples, macrocephaly, and talipes equinovarus.

More than two-thirds of 46,XY campomelic dysplasia patients are sex reversed, developing as phenotypic females due to a failure to form testes. The degree of sex reversal can vary, with the most common outcome being normal phenotypic female with dysgenic ovaries. Dominant mutations in the transcription factor SOX9 are responsible for both the skeletal and the sex development phenotypes.

Mutation analysis and functional assays suggest that the phenotypes result from haploinsufficiency due to loss-of-function mutations of a single SOX9 allele. SOX9 mutations apparently do not cause sex reversal in the absence of CD skeletal defects.

SOX9 appears to be a critical component of the developmental pathways of both cartilage formation and testis formation, functioning independently in the development of these two dissimilar tissues.

SOX9 mutations cause a loss of protein function that leads to a failure to propagate the appropriate developmental signals in both chondrogenic tissue and the indifferent gonad. Expression of SOX9 is the earliest marker of cartilage differentiation and is required for cartilage formation. The SOX9 protein is expressed during embryonic chondrogenesis and directly regulates type II collagen gene expression in chondrocytes.

SOX9 may also be directly involved in regulation of type XI collagen, which is coexpressed with type II collagen, both collagens being essential for normal cartilage development and skeletal morphogenesis.

In chimeric mice, cells with homozygous deletions of Sox9 are excluded from all cartilages and do not express chondrocyte-specific markers, showing the essential role of Sox9 in chondrogenesis and cartilage formation. During mouse gonadal development, Sox9 is expressed in both XX and XY embryos in the undifferentiated genital ridge.

In XY embryos, Sox9 is up-regulated coincident with the onset of expression of Sry , the Y chromosome testis determination factor, and continues to be expressed at high levels in developing testes, with expression limited to the Sertoli cells.

At the corresponding time in XX embryos, Sox9 expression is down-regulated. This is the earliest difference in gene expression known between males and females other than that of Sry itself. The timing and sexually dimorphic expression of Sox9 in differentiating gonads, and its involvement in transactivation of a testis-specific gene, suggests a critical role for SOX9 in testis determination. This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.

About MyAccess If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Sign in via OpenAthens.

Sign in via Shibboleth. Clinical Sports Medicine Collection. Search Advanced search allows to you precisely focus your query. Search within a content type, and even narrow to one or more resources. You can also find results for a single author or contributor. Valle D, Beaudet A.

David Valle, et al. Accessed October 28, Username Please enter User Name. Password Please enter Password. Use this site remotely Bookmark your favorite content Track your self-assessment progress and more! View All Subscription Options. Pop-up div Successfully Displayed This div only appears when the trigger link is hovered over. This site uses cookies to provide, maintain and improve your experience.

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