Pre-Expression Evaluation of Spondyloepiphyseal Dysplasia Tarda By Sedlin Gene Analysis. G.S. Gottesman^1,2, S. Mumm³, X. Zhang³, W.H. McAlister⁴, M.N. Podgornik¹, M.P. Whyte^1,3. 1) Metabolic Research Unit, Shriners Hosp Children, St Louis, MO; 2) Div Medical Genetics, Saint Louis Univ Sch Medicine, St Louis, MO; 3) Div Bone Mineral Diseases, Wash Univ Sch Med, St Louis, MO; 4) Dept Radiology, St Louis Childrens Hosp, St Louis, MO.
   Spondyloepiphyseal dysplasia tarda (SEDT) is a X-linked recessive disorder that presents during childhood with back pain and short stature in boys. As we have reported (Medicine 78:9-25,1999), heterozygous women can manifest subtle radiographic changes. However, skeletal radiographs of affected (hemizygous) boys are normal during infancy and early childhood. In 1999, 2 bp deletions were identified in a gene designated Sedlin in 3 Australian families with SEDT (Nat Genet 22:4, 400-404 1999). Although there is no established medical treatment for this condition, pre-expression diagnosis by sedlin gene analysis could be beneficial, allowing appropriate counseling against physical activities injurious to the spine and the joints, especially those of the lower limbs.
   After an orthopedist referred a 15-year-old young man (proband) with dysplastic changes of the spine, we established a diagnosis of SEDT. He was from a large kindred with previously undiagnosed SEDT involving at least 5 generations. A unique 2 bp deletion in exon 5 was found on molecular analysis by PCR amplification and sequencing of all the coding exons. We then studied a nuclear family from within the kindred (proband's maternal aunt and her 3 sons). The woman was a potential carrier. Subtle shaping abnormalities of her pelvis and knees on skeletal radiographs supported this possibility. Radiographs of the spine and pelvis of the 2 younger boys (ages 2 and 5) showed no changes of SEDT, but those of the eldest son (age 8) had clear-cut evidence of the disorder. Molecular testing demonstrated the mother and only her eldest son had the same 2 bp deletion in exon 5. Molecular testing for Sedlin gene abnormalities enables pre-symptomatic diagnosis prior to radiographic demonstration of the disorder. Perhaps, cautions early on to minimize physical strain to the spine and joints will ameliorate the eventual manifestations of the disorder.