X-linked spondyloepiphyseal dysplasia tarda: molecular cause of a heritable platyspondyly.

STUDY DESIGN Report of a family affected with X-linked spondyloepiphyseal dysplasia tarda with special respect to radiologic alterations of the spine from puberty to the forth decade and to molecular analysis of the underlying genetic defect. OBJECTIVES To report the typical radiologic presentation of patients with X-linked spondyloepiphyseal dysplasia tarda and the diagnostic tool of mutation screening for that disease in order to avoid confusion with similar occurrences. SUMMARY OF BACKGROUND DATA Spondyloepiphyseal dysplasia tarda is a genetically heterogeneous disorder that frequently manifests itself with back pain starting around puberty. The X-linked recessive form (X-linked spondyloepiphyseal dysplasia tarda) affects males and is clinically characterized by an arm span markedly exceeding total height, a barrel chest deformity, and early development of degenerative joint disease. The disorder is caused by mutations in the SEDL gene located on Xp22.12-p22.31. METHODS Radiologic alterations of the cervical, thoracal, and lumbar spine were assessed in the affected family members and one suspected female carrier in correlation to age. All 6 exon codings for the SEDL gene were analyzed by primer cycle sequencing. RESULTS In 3 male patients from a French family, we identified a 5 base pair deletion in SEDL, exon 5 at position 267-271 (delAAGAC). Carrier status for the mutation could be confirmed in one female member of the family, which is inconspicuous in terms of spine and joint diseases. Radiologic abnormalities of the patients comprised generalized platyspondyly, a hump-shaped deformity of cervical, thoracal, and lumbar vertebral bodies as well as signs of retrospondylophytes, osteochondrosis, and spondylarthrosis. CONCLUSIONS X-linked spondyloepiphyseal dysplasia tarda should be kept in mind as a differential diagnosis in men with early onset of back pain and radiologic abnormalities of the vertebral bodies comprising platyspondyly and a central hump.