Duplication at 19q13.32q13.33 Segregating with Neuropsychiatric Phenotype in a Three-Generation Family: Towards the Definition of a Critical Region

Chromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopmental disorders, often acting as moderate- penetrance risk factors, possibly inherited from unaffected parents. We describe a three- generation family with non-syndromic neuropsychiatric features segregating with a novel 19q13.32q13.3 microduplication. The propositus was a 28-month male ascertained for psychomotor delay, with no dysmorphic features or malformations. His mother had Attention- Deficit/Hyperactivity Disorder and learning disability. The maternal uncle had intellectual disability. Chromosomal microarray analysis identified a 969 kb 19q13.32q13.3 microduplication in the proband. The variant segregated in the mother, the uncle, and the maternal grandmother of the proband, who also presented neuropsychiatric disorders. Fragile-X Syndrome testing was negative. Exome Sequencing did not identify Pathogenic/Likely pathogenic variants. Imbalances involving 19q13.32 and 19q13.33 are associated with neurodevelopmental delay. A review of the reported microduplications allowed to propose BICRA (MIM*605690) and KPTN (MIM*615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains. The peculiarities of this case are the small extension of the duplication, the three-generation segregation and the full penetrance of the phenotype.