ß 2006 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 140A:1203–1207 (2006) Clinical Report De Novo Pure 12q22q24.33 Duplication: First Report of a Case With Mental Retardation, ADHD, and Dandy-Walker Malformation S. Cappellacci, 1 S. Martinelli, 1 R. Rinaldi, 1 E. Martinelli, 1 P. Parisi, 2 B. Mancini, 1 R. Pescosolido, 1 and P. Grammatico 1 * 1 Medical Genetics, Experimental Medicine and Pathology Department, University ‘‘La Sapienza’’, S. Camillo-Forlanini Hospital, Rome, Italy 2 Child Neurology Unit—Pediatric Department, University ‘‘La Sapienza’’, ‘‘Sant’Andrea’’ Hospital, Rome, Italy Received 29 July 2005; Accepted 19 February 2006 We present a patient with a de novo 12q nonmosaic pure duplication characterized by multiple minor anomalies and Dandy – Walker malformation. A neurological and behavioral assessment revealed psychomotor retardation and attention deficit/hyperactivity disorder (ADHD), with neurobehavioral abnormalities (auto- and heteroaggressive behavior). Fluox- etine therapy in this case markedly improved the neurobe- havioral profile, with a decreased level of aggression. To define the extension of the duplicated region, we performed FISH analyses by using YAC probes. The analyses revealed a tandem duplication of the 12q22q24.33 region, with the proximal breakpoint located between 96.5 and 97.6 cM and the distal one between 154 and 161 cM. This is the first case of pure de novo duplication involving the 12q22q24.33 region. To better define the clinical phenotype associated with 12q partial duplication, we compared our case with the four patients with similar pure duplications previously described. ß 2006 Wiley-Liss, Inc. Key words: ADHD; Dandy–Walker; 12q duplication; FISH How to cite this article: Cappellacci S, Martinelli S, Rinaldi R, Martinelli E, Parisi P, Mancini B, Pescosolido R, Grammatico P. 2006. De novo pure 12q22q24.33 duplication: First report of a case with mental retardation, ADHD, and Dandy-Walker malformation. Am J Med Genet Part A 140A:1203–1207. INTRODUCTION The phenotypes of both 12p and 12q duplications are described in the literature [El-Shanti et al., 1997]. Structural interstitial abnormalities involving the long arm of chromosome 12 have been reported very rarely, and it has been proposed that significant alterations of the long arm are likely to be lethal [Dixon et al., 1993]. Most cases of 12q partial duplication involve the 12q24 ! qter region, due to segregation of a parental balanced translocation [Lagier-Tourenne et al., 2004]. To our knowledge, only a few patients with pure 12q duplications have been described [Harrod et al., 1980; Ieshima et al., 1984; Dixon et al., 1993; Houfflin et al., 1993; El-Shanti et al., 1997; Ireland et al., 2004]. Here we present the case of a young man with mental retardation, attention- deficit/hyperactivity disorder (ADHD), Dandy–Walker malformation, and multiple minor anomalies, who has a 12q22q24.33 duplication, previously undescribed, which we characterized by FISH, using YAC probes. To contribute to the identification of the character- istic clinical features associated with 12q partial duplication, we review the literature and compare our case with those already described. CLINICAL REPORT A 8-year-old, right-handed, Italian male, born uneventfully as the second child of nonconsangui- neous healthy parents, was admitted to the emer- gency pediatrics unit because of the onset of migraine (proceeded by visual auras) unresponsive to analgesic therapy and associated with confusion. *Correspondence to: Prof. P. Grammatico, Medical Genetics, Experi- mental Medicine and Pathology Department, University ‘‘La Sapienza’’, S. Camillo-Forlanini Hospital, Circ.ne Gianicolense n. 87, 00152 Rome, Italy. E-mail: paola.grammatico@uniroma1.it DOI 10.1002/ajmg.a.31219