CLINICAL REPORT Characterization of Double Ring Chromosome 4 Mosaicism Associated With Bilateral Hip Dislocation, Cortical Dysgenesis, and Epilepsy Yasemin Soysal, 1 * Sevim Balcı, 2 Kuyas ¸ Hekimler, 1 Thomas Liehr, 3 Elisabeth Ewers, 3 Jacqueline Schoumans, 4 The-Hung Bui, 4 Fadime Mutlu _ Ic ¸duygu, 1 Nadezda Kosyakova, 3 and Necat _ Imirzalıo glu 1 1 Afyon Kocatepe University Faculty of Medicine, Department of Medical Genetics, Afyonkarahisar, Turkey 2 Hacettepe University Faculty of Medicine, Department of Clinical Genetics, Ihsan Do gramacı Children’s Hospital, Ankara, Turkey 3 Jena University Hospital, Institute of Human Genetics and Anthropology, Jena, Germany 4 Department of Molecular Medicine and Surgery, Clinical Genetics Unit, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden Received 13 May 2009; Accepted 16 July 2009 We present the clinical and molecular findings in a Turkish child with a de novo mosaic ring derived from chromosome 4 with multiple cell-lines; the karyotype was 46,XY,r(4)[83]/ 45,XY, 4[6]/47,XY,r(4),þr(4)[5]/48,XY,r(4),þr(4),þdic r(4)- [1]/46,XY[5]. The patient is a 20-month-old male who was the first pregnancy of nonconsanguineous parents. The baby was delivered at term with a birth weight of 1,700 g (<3rd centile) and a length of 46 cm. The baby had feeding difficulties and vomiting problems. He started walking at age 2 years and delayed language was observed. Facial appearance was normal, but the ears were large with abnormal structure. The hands showed bilateral clinodactyly of the 5th fingers. He had mild mental retardation, and epilepsy. Analysis of chromosomes showed 46,XY,r(4)(::p16.3 ! qter::)[67]/46,XY,r(4;4)(::p16.3 ! qter::p16.3 ! qter::)[2]/46,XY[3] by multicolor banding (MCB) technique. Array CGH delineated the size of the terminal dele- tion as 900 kb in 4p16.3. The Wolf–Hirschhorn critical region was preserved even though our patient had mild mental and motor retardation. While the mosaicism of the ring 4 could affect the phenotype, the deleted 900 kb distal deletion and clinical features of the patient may provide further insight into charac- teristic phenotype of the 4p related syndromes. Ó 2009 Wiley-Liss, Inc. Key words: ring chromosome 4; mosaicism; Wolf–Hirschhorn syndrome (WHS); hip dislocation; epilepsy; multicolor banding (MCB); array CGH analysis INTRODUCTION Ring chromosomes arise by breakage in both arms of a chromo- some, with fusion of the points of fracture and loss of the distal fragments [Lee et al., 2005]. If there is no apparent deletion of the telomeric ends, patients with ring chromosomes often exhibit growth failure with or without minor anomalies [Sigurdardottir et al., 1999]. Ring chromosome frequency is 1 in 25,000 recognized conceptions, and rings can be seen with all human chromosomes [Jacobs, 1981]. Instability of ring chromosomes may cause loss of the ring, double sized rings, or multiple copies of the ring; double sized (dicentric) rings derived from chromosome 4 have been reported before by Lee et al. [2005], Chen et al. [2007], and Kim et al. [2009]. Cases with ring chromosome 4 have some common clinical features, including low birth weight, growth retardation, Grant sponsor: Friedrich Schiller University Jena; Grant number: 21007091; Grant sponsor: DFG; Grant number: LI 820/14-1. This case was presented in ESHG 2009 Vienna, May 23–26, 2009 within the Poster Section P03 Cytogenetics by the poster number of P03.107. *Correspondence to: Yasemin Soysal, Ph.D., Assistant Professor, Afyon Kocatepe University Faculty of Medicine, Department of Medical Genetics, Morfoloji Binası Ali Cetinkaya Kamp€ us€ u Izmir yolu 8.km., 03200 Afyonkarahisar, Turkey. E-mail: yasemin_soysal@yahoo.com Published online 16 November 2009 in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/ajmg.a.33069 How to Cite this Article: Soysal Y, Balcı S, Hekimler K, Liehr T, Ewers E, Schoumans J, Bui T-H, _ Ic ¸duygu FM, Kosyakova N, _ Imirzalıo glu N. 2009. Characterization of double ring chromosome 4 mosaicism associated with bilateral hip dislocation, cortical dysgenesis, and epilepsy. Am J Med Genet Part A 149A:2782–2787. Ó 2009 Wiley-Liss, Inc. 2782