ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:1972 – 1976 (2008) Clinical Report Spondylocostal Dysostosis in a Pregnancy Complicated by Confined Placental Mosaicism for Tetrasomy 9p David Coman, 1,2 Sonya Bacic, 3 Amber Boys, 1,2 Duncan B. Sparrow, 4 Sally L. Dunwoodie, 4,5 Ravi Savarirayan, 1,2,3 and David J. Amor 1,2,3 * 1 Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne, Australia 2 Department of Paediatrics, University of Melbourne, Melbourne, Australia 3 Tasmanian Clinical Genetics Service, Royal Hobart Hospital, Hobart, Australia 4 Victor Chang Cardiac Research Institute, Sydney, Australia 5 Faculties of Medicine and Science, University of New South Wales, Sydney, Australia Received 22 October 2007; Accepted 5 February 2008 The spondylocostal dysostoses (SCD) are a clinically and genetically heterogeneous group of disorders characterized by defects of vertebral segmentation and rib abnormalities. We report on the diagnosisof two siblingswith SCD. Diagnosiswas firstmade in a female infant following a pregnancy that was complicated by early fetal hydrops and a nuchaltranslucency of 8.2 mm in the firstrimester. The clinical picture was complicated by the co-existent diagnosis of confined placental mosaicism (CPM) for tetrasomy 9p. To our knowledge, this is the first report of CPM for tetrasomy 9p. Postnatally the diagnosis of SCD was made on the basis of radiographic findings comprising multiple anomalies of the cervical and thoracic vertebrae and multiple fused and dysplastic ribs. Radiographic investigation of otherfamily members showed that the infant’s 4-year-old sibling had fusion of four ribs on the right side, indicating a less severe form of SCD. Testing of the genes DLL3, MESP2, and LFNG did not identify a mutation, suggesting that the siblings may have a new molecular subtype of SCD. ß 2008 Wiley-Liss, Inc. Key words: spondylocostal dysostosis; mosaic tetrasomy 9p; confined placental mosaicism; prenatal diagnosis How to cite this article: Coman D, Bacic S, Boys A, Sparrow DB, Dunwoodie SL, Savarirayan R, Amor DJ. 2008. Spondylocostal dysostosis in a pregnancy complicated by confined placental mosaicism for tetrasomy 9p. Am J Med Genet Part A 146A:1972–1976. INTRODUCTION The spondylocostal dysostoses (SCD) are a group of disorders that predominantly affect development of the vertebrae and ribs. The main radiological featuresare vertebralsegmentation defects with contiguous involvementof multiple segments (>10),a generally symmetrical thoracic cage and rib number, and the presence of intercostal rib fusion [Turnpenny etal., 2007].Clinical manifestations of SCD include truncal shortening, scoliosis,and restrictive lung defects. To date, the spondylocostal dysostoses have been classified into three Types corresponding to the presence of autosomal reces- sive mutations in the genes DLL3 (Type 1), MESP2 (Type 2),and LNFG (and Type 3) [Whittock et al., 2004; Sparrow et al., 2006; Turnpenny et al., 2007]. All three genesencode components of the NOTCH signaling pathway [Turnpenny et al., 2003]. To date, molecularanalysis has been restricted to a small number of families and it is likely that other genes for SCD willbe identified in due course. Families with SCD following apparently autosomal dominant inheritance have also been reported [Lorenz and Rupprecht, 1990]. Here we report on two siblings with SCD in which testing ofthe three known SCD genes failed to detected a pathogenicmutation.In one of the siblings, the detection of confined placental mosai- cism (CPM) for tetrasomy 9p was almost certainly a coincidental finding. Grant sponsor: National Health and Medical ResearchCouncil (NHMRC) (Australia); Grant number: 404804. *Correspondence to: Dr. David J. Amor, Murdoch Childrens Research Institute Flemington Rd, Parkville, Vic. 3052, Australia. E-mail: david.amor@mcri.edu.au DOI 10.1002/ajmg.a.32299