Different Chromosomal Aberrations for One Entity: 9p Duplication Syndrome

9p duplication is a clinically recognized syndrome (S.dup9). It includes microcephaly and a particularly recognizable dysmorphic features. Here, we report the clinical and cytogenetic results in three Tunisian patients with different chromosomal rearrangements resulting in complete 9p duplication in 2 patients and tetrasomy 9p in the third. At physical examination, our patients presented common features including low-implanted ears, horizontal palpebral fissures, hypertelorism and microretrognathia. They also had Microcephaly and psychomotor delay. Palio cleft palate and clubfeet were observed in one patient. Chromosome rearrangements were characterized using conventional karyotype, fluorescent in situ hybridization (FISH) and array comparative genomic hybridization (array CGH). The karyotype showed three different de novo rearrangements: a supernumerary chromosome marker (MCS) classified as a derivative of the short arm of chromosome 9 (1), isochromosome 9p (2) and a duplication of the short arm of chromosome 9 (3). Array CGH allowed delimiting the extent of duplication to 38Mb from 9p13.1 to 9p24.3 in two patients. Unlike the majority of cases reported in the literature, duplication is not secondary to parental translocation. It appeared de Novo in all three patients suggesting that an accident occurred during meiosis. S.dup9 has a minimal critical region 9p22.3-9p22.2 responsible for the observed phenotype. A variety of morbid genes such as KANK1, GLIS3, KCNV2, and SLC1A1 are known to be involved in cytoskeletal formation, embryonic development, and cell signaling. At 9p22, the CER1 gene expressed in the anterior mesoderm at the embryo gastrula stage and the FREM1 gene, acting in epidermal adhesion, could contribute to epithelial embryo deregulation leading to orofacial abnormalities. Nevertheless, it is necessary to study the dosage effect of other genes in this region to have a better genotype-phenotype correlation.