Novel duplication on chromosome 16 (q12.1-q21) associated with behavioral disorder, mild cognitive impairment, speech...

We report on the 10-year follow-up and clinical, cytogenetic, and molecular investigation of a girl admitted for evaluation because of speech delay, learning difficulties, aggressive behavior, and dysmorphic facial features that included high forehead, round face, epicanthic folds, low-set dysplastic ears, flat nasal bridge, long flat philtrum, thin upper lip, small mouth, and short neck. The analysis of high-resolution GTG- and CTG-banding chromosomes suggested a de novo direct duplication of 16q12-q21 region and fluorescence in situ hybridization analysis with whole-chromosome specific 16 probe confirmed that the duplicated genetic material originated from the chromosome 16. Subsequently, array-based comparative genomic hybridization analysis with a≈75 kb resolution showed a 9.92 Mb gain on the long arm of chromosome 16 at bands q12.1 through q21. To the best of our knowledge, this is the first case of duplication 16q12.1q21 described in literature. Several genes within the duplicated region are possibly correlated with clinical features present in our patient. Clinical and cytogenetic findings were compared with the small number of reported patients with pure duplications 16q, partially overlapping the one in our patient. Clinical phenotype seems to be distinctive between the proximal-intermediate and intermediate-distal regions of the long arm of the chromosome 16. In particular, we observed a set of dysmorphic features that could present a characteristic dup 16q11.2-q13 phenotype. The present study illustrates the advantages of an integrative approach using both conventional and molecular techniques for the precise characterization and genotype-phenotype correlation in patients with dysmorphism, behavioral problems, and learning difficulties.