RESEARCH ARTICLE Clinical, Cytogenetic and Molecular-Cytogenetic Characterization of a Patient With a De Novo Tandem Proximal-Intermediate Duplication of 16q and Review of the Literature Fortunato Lonardo, 1 * Lucia Perone, 2 Marianna Maioli, 1 Maria Ciavarella, 1 Roberto Ciccone, 3 Matteo Della Monica, 1 Cinzia Lombardi, 1 Luisa Forino, 4 Giuseppina Cantalupo, 1 Lucia Masella, 1 and Francesca Scarano 1 1 A.O.R.N. ‘‘G. Rummo’’, U.O.C. di Genetica Medica, Benevento, Italy 2 Telethon Institute of Genetics and Medicine (TIGEM), Napoli, Italy 3 Dipartimento di Patologia Umana ed Ereditaria, Universit a di Pavia, Sezione di Biologia Generale e Genetica Medica, Pavia, Italy 4 A.I.A.S., Sezione di Nola, Cicciano (NA), Italy Received 9 May 2010; Accepted 29 November 2010 Partial trisomy 16 is rare and most of the reported cases are secondary to chromosome rearrangements resulting in concurrent monosomies or trisomies of a second chromosome. Only a few patients survive the neonatal period and the duplication of the long arm seems to be mainly responsible for the prenatal lethality of the full trisomy 16. The reported patients with a partial 16q trisomy have a wide spectrum of congenital anomalies that include dys- morphic features, central nervous system malformations, failure to thrive, and club feet. The patients with duplications of proximal 16q frequently have short stature, developmental delay, speech delay, learning difficulties, and mild to severe behavioral problems. Here we describe a patient with an inverted de novo tandem duplication of 16q with breakpoints evaluated in detail by molecular-cytogenetic techniques. Main clinical features include postural, motor and speech delay with severe learning difficulties and behavioral problems, obesity, microcephaly, and mild dys- morphic features. In the report we attempt to classify the few reported patients with pure partial duplications of 16q in more narrow and homogeneous groups: proximal, proximal-intermedi- ate, intermediate, and intermediate-distal duplications. Moreover, we emphasize the importance of proper cytogenetic investigation and complete molecular cytogenetic refinement in all cases with a suspected chromosomal anomaly. Ó 2011 Wiley-Liss, Inc. Key words: 16q11.2!q22; bacterial artificial chromosomes; fluorescent in situ hybridization; oligonucleotide microarrays; speech delay; tandem duplication INTRODUCTION At conception, trisomy 16 is the most frequent chromosome abnor- mality in man [Wolstenholme, 1995]. It accounts for approximately 15% of all chromosomally abnormal and one-third of all trisomic spontaneous abortions [Hassold and Jacobs, 1984]. The embryo- fetal losses mostly occur between 8 and 15 weeks of pregnancy and embryos are minimally developed, or there is an empty sac. Earlier reports of newborn with ‘‘trisomy 16’’ could not be confirmed by later banded studies, and most likely these cases represent various structural aberrations [Schinzel, 2001]. Thus, complete trisomy 16 can be considered to be lethal early in pregnancy, but viable mosaic trisomy 16 have been reported [Coman et al., 2010]. Partial trisomy 16 is rare and the phenotypic effects are difficult to study because most of the reported cases are secondary to chromosome rearrangements resulting concurrently *Correspondence to: Fortunato Lonardo, A.O.R.N. ‘‘G. Rummo’’, U.O.C. di Genetica Medica, S.S. di Citogenetica Medica e Genetica Molecolare, Via dell’Angelo, 1, I-82100 Benevento, Italy. E-mail: fortunato.lonardo@ao-rummo.it, fortunato.lonardo@libero.it Published online 17 March 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.33852 How to Cite this Article: Lonardo F, Perone L, Maioli M, Ciavarella M, Ciccone R, Monica MD, Lombardi C, Forino L, Cantalupo G, Masella L, Scarano F. 2011. Clinical, cytogenetic and molecular- cytogenetic characterization of a patient with a de novo tandem proximal-intermediate duplication of 16q and review of the literature. Am J Med Genet Part A 155:769–777. Ó 2011 Wiley-Liss, Inc. 769