Since the large implementation of array-based comparative genomic hybridization (array-CGH) in the diagnostic workup of mental retardation (MR), new recurrent copy number variations (CNVs) and novel microdeletion/microduplication syndromes have been described. As more patients are identified carrying microdeletion/microduplication, it has become clear that some genomic disorders have high penetrance but a wide range of phenotypic severity. The recurrent CNVs that are found in multiple unrelated patients are usually associated with a broader range of phenotypes. For instance, the recurrent deletion of the chromosomal region 1q21.1 has been associated with a wide range of phenotypes: from mild to moderate MR, dysmorphic features, microcephaly, cardiac abnormalities and cataract to normal phenotype (Mefford et al. 2008). The same deletions are sometimes transmitted from apparently unaffected parents and are found in 0.02% of controls. Likewise, the most common 16p11.2 microdeletion syndrome has been identified with a similar prevalence (0.3– 0.7%) in large cohorts of patients with intellectual disability or other developmental problems (Bijlsma et al. 2009; Rosenfeld et al. 2010; Shinawi et al. 2010) and in ~0.6% (varying from 0.3% to 1% based on various studies) of all patients with autism spectrum disorder (ASD) (Kumar et al. 2008; Marshall et al. 2008; Weiss et al. 2008). Besides, some individuals carrying the deletion show no obvious developmental or physical abnormalities (Ghebranious et al. 2007; Bijlsma et al. 2009; Shimojima et al. 2009). The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism. This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion and the factors that modify the clinical phenotypes are currently unknown. Several recent reports suggest a large number of candidate CNVs non-specific to disease involved in the expression of different behaviour phenotypes, including MR, ASD and schizophrenia (SZ) (Guilmatre et al. 2009; Shinawi et al. 2010; Balasubramanian et al. 2011). This implies the existence of shared biological pathways between these neurodevelopmental conditions. The dysfunction of specific neuronal networks of each clinical condition most likely depends on additional genetics, epigenetics and environmental factors which remain to be characterised. Here, we present the clinical and molecular data of two unrelated patients with overlapping 16p11.2 deletions and discuss the function of the genes in this region and the effects of their haploinsufficiency on the clinical features described in the patients. Ž. Ciuladaitė (*) : J. Kasnauskienė : L. Cimbalistienė : E. Preiksaitienė :V. Kucinskas Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University, Santariskių st. 2, 08661 Vilnius, Lithuania e-mail: zivile.ciuladaite@mf.vu.lt