Chromosome 17p13.3 is a region of genomic instability that is linked to 
different rare neurodevelopmental genetic diseases, depending on whether a 
deletion or duplication of the region has occurred. Chromosome microdeletions 
within 17p13.3 can result in either isolated lissencephaly sequence (ILS) or 
Miller-Dieker syndrome (MDS). Both conditions are associated with a smooth 
cerebral cortex, or lissencephaly, which leads to developmental delay, 
intellectual disability, and seizures. However, patients with MDS have larger 
deletions than patients with ILS, resulting in additional symptoms such as poor 
muscle tone, congenital anomalies, abnormal spasticity, and craniofacial 
dysmorphisms. In contrast to microdeletions in 17p13.3, recent studies have 
attracted considerable attention to a condition known as a 17p13.3 
microduplication syndrome. Depending on the genes involved in their 
microduplication, patients with 17p13.3 microduplication syndrome may be 
categorized into either class I or class II. Individuals in class I have 
microduplications of the YWHAE gene encoding 14-3-3ε, as well as other genes in 
the region. However, the PAFAH1B1 gene encoding LIS1 is never duplicated in 
these patients. Class I microduplications generally result in learning 
disabilities, autism, and developmental delays, among other disorders. 
Individuals in class II always have microduplications of the PAFAH1B1 gene, 
which may include YWHAE and other genetic microduplications. Class II 
microduplications generally result in smaller body size, developmental delays, 
microcephaly, and other brain malformations. Here, we review the phenotypes 
associated with copy number variations (CNVs) of chromosome 17p13.3 and detail 
their developmental connection to particular microdeletions or 
microduplications. We also focus on existing single and double knockout mouse 
models that have been used to study human phenotypes, since the highly limited 
number of patients makes a study of these conditions difficult in humans. These 
models are also crucial for the study of brain development at a mechanistic 
level since this cannot be accomplished in humans. Finally, we emphasize the 
usefulness of the CRISPR/Cas9 system and next generation sequencing in the study 
of neurodevelopmental diseases.