RESEARCH LETTER 18q22.3 ! 18q23 Deletion Syndrome and Cleft Palate James D. Eudy, 1 Diane L. Pickering, 2 Richard Lutz, 2 Kristal Platt, 3 Bhavana J. Dave, 2 Ann Haskins Olney, 2 and Warren G. Sanger 2 * 1 Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 2 Department of Pediatrics and Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska 3 Boys Town National Research Hospital, Omaha, Nebraska Received 14 January 2009; Accepted 22 December 2009 TO THE EDITOR: The 18q22 ! qter deletion syndrome was first described by De Grouchy et al. [1964]. Multiple congenital anomalies known to be associated with the syndrome include microcephaly, short stature, congenital aural atresia (CAA), cleft palate with or without cleft lip (CL/CP), foot deformations, epilepsy, and developmental delay. Since the initial observation of the anomalies associated with 18q deletions, research groups have analyzed cohorts of patients with terminal 18q deletions to better understand the phenotypes associ- ated with the different chromosomal breakpoints [Kline et al., 1993; Cody et al., 1999]. The advent of high-resolution microarray comparative hybridization (aCGH) has facilitated the generation of a phenotype/genotype map for the syndrome [Veltman et al., 2003; Dostal et al., 2006; Feenstra et al., 2007; Cody et al., 2009]. In this research letter we describe a family in which the maternal half- siblings have del(18)(q22.3q23) and similar clinical findings. The cytogenetic data further refines a region associated with the cleft palate component of the phenotype. The patient is an 8-year-old female who was referred for aCGH studies because of cleft soft palate, short stature, developmental delay, speech delay, bitemporal narrowing, conductive hearing loss, and abnormal external ears and external auditory canals. Also present was a strong family history of developmental delays and mental retardation, with similar unique recurrent birth defects in three half-siblings and the mother (Fig. 1) The patient was initially evaluated at 16 months of age because of cleft palate and at that time had normal high-resolution chromosome analysis and 22q FISH studies. High-resolution aCGH studies utilizing the human CGH 4  44K array (Agilent Technologies, Wilmington, DE) defined a 4.1 Mb deletion at 18q22.3-q23 from linear location 70.5–74.6 Mb (Fig. 2). Confirmatory FISH studies with BAC clone RP11-90L3 were positive for a deletion in this patient and her two half-siblings with similar clinical findings. The biological mother, a sibling and an additional half-sibling reportedly had similar clinical findings but were unavailable for study. In this study we report six cases with clinical findings consistent with 18q deletion syndrome. Cytogenetic studies were performed on three maternal half-siblings and all three had identical 18q deletion. Clinical findings in all six cases which included conductive hearing loss, aural atresia, developmental delay, delayed speech, and bitemporal narrowing, were consistent with 18q deletion syndrome. A large study of 18q deletion patients and associated genotype/phenotype mapping identified two regions associated with CL/CP; a large proximal region located from 25.2 to 42.9 Mb on 18q.12.1-q12.3, and a smaller terminal region of 7.2 Mb in size on 18q22.2-q23 located between 67.7 and 74.9 Mb [Feenstra et al., 2007]. A recent review of cases by Dostal et al. [2009] narrowed the critical region to a 5 Mb region between D18S879 and D18S1141 which contains 17 known genes. The patient in this research letter presented with clefting of the soft palate, and the associated deletion was defined as a 4.1 Mb region between 70.5 and 74.6 Mb, which further refines the terminal critical region for CP on 18q, and reduces the number of candidate genes from 17 to nine. Grant sponsor: UNMC Cytogenetics Research Fund. *Correspondence to: Warren G. Sanger, PhD, Department of Pediatrics and Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68198-5440. E-mail: wgsanger@unmc.edu Published online 23 March 2010 in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/ajmg.a.33336 How to Cite this Article: Eudy JD, Pickering DL, Lutz R, Platt K, Dave BJ, Olney AH, Sanger WG. 2010. 18q22.3 ! 18q23 Deletion syndrome and cleft palate. Am J Med Genet Part A 152A:1046–1048. Ó 2010 Wiley-Liss, Inc. 1046