ß 2007 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:110–115 (2008) Clinical Report Cytogenetic and Array CGH Characterization of an Intrachromosomal Complex Rearrangement of 4q in a Patient With a 4q-Phenotype Alberto Sensi, 1 * Paolo Prontera, 1,2 Barbara Buldrini, 1 Silvia Palma, 3 Vincenzo Aiello, 1 Rita Gruppioni, 1 Elisa Calzolari, 1 Stefano Volinia, 4 and Alessandro Martini 3 1 Genetica Medica, Universita ` di Ferrara, Ferrara, Italy 2 Genetica Medica, Universita ` di Perugia, Perugia, Italy 3 Audiologia, Universita ` di Ferrara, Ferrara, Italy 4 Istologia ed Embriologia Generale, Universita ` di Ferrara, Ferrara, Italy Received 3 April 2007; Accepted 20 July 2007 We report on a 3-year-old child who presented a de novo rearrangement of chromosome 4, detected on GTG banding and characterized by array CGH and FISH, as a complex intrachromosomal rearrangement with three deletions: del(q32.1q32.2), del(q33q34.1), del(q35.2), one tandem duplication dup(q34.3q35.1) and short normal regions in between. The study of karyotype – phenotype correlations in this and other patients with deletions of 4q suggests 4q33q34.1 as a candidate region for 4q-syndrome and for craniofacial development. ß 2007 Wiley-Liss, Inc. Key words: array-CGH; complex intrachromosomal rear- rangement; chromosome 4; deletion; duplication; 4q- syndrome How to cite this article: Sensi A, Prontera P, Buldrini B, Palma S, Aiello V, Gruppioni R, Calzolari E, Volinia S, Martini A. 2008. Cytogenetic and array CGH characterization of an intrachromosomal complex rearrangement of 4q in a patient with a 4q-phenotype. Am J Med Genet Part A 146A:110 –115. INTRODUCTION Complex chromosomal rearrangements (CCR) have been defined as constitutional structural rear- rangements involving three or more breakpoints [Houge et al., 2003; Weise et al., 2003]. CCRs involving single chromosomes are rare, but recent evidence from array CGH suggests that such rearrangements are not as uncommon as previously thought on the basis of classical cytogenetic techni- ques. Even terminal deletions or other apparently simple chromosomal rearrangements may actually contain a hidden complexity at the molecular level [Ciccone et al., 2005; De Vries et al., 2005; Gajeka et al., 2006]. Here we report on the detailed cytogenetic chara- cterization by array CGH of a CCR involving the long arm of chromosome 4, identified in a male infant with a distinctive phenotype of multiple congenital abnormalities and global development delay. CLINICAL REPORT The patient was an only child born to healthy unrelated parents. The family history was unremark- able. The baby was delivered at 40 weeks by Cesarean for oligohydramnios and signs of fetal distress. Birth weight was 2,480 g (<10th centile), length was 48.0 cm (50th centile), and head circum- ference (OFC) 31.3 cm (<10th centile). The child showed neonatal hypotonia, craniofacial anomalies including a large anterior fontanel and aural atresia, congenital laryngeal stridor, ostium secundum atrial septal defect, and patent ductus arteriosus (surgically treated within 2 months of birth), bilateral cryptorch- idism (testes in the inguinal canals) and diaphrag- matic hernia. Subsequent examinations showed global developmental delay and delayed closure of the anterior fontanel. Brain magnetic resonance imaging did not detect any anomaly. CT of the medial and inner ears and 3D CT of the cranium showed trigonocephaly, bilateral absence of external *Correspondence to: Alberto Sensi, M.D., Genetica Medica, Universita ` di Ferrara, Via Fossato di Mortara 74, I 44100 Ferrara, Italy. E-mail: sna@unife.it DOI 10.1002/ajmg.a.32059