Multiple phenotypic features have been associated with 16p12.2 deletion (previously known as 16p12.1 deletion). Although not all clinical features are completely recognizable in very young subjects, most subjects show developmental delay and learning disability.

Affected individuals may present speech delay, hypotonia, craniofacial and skeletal abnormalities, growth retardation, microcephaly, cardiac disease. Furthermore, seizure disorders are present and may manifest in several forms, including West syndrome, febrile seizures or seizure-like episodes. Psychiatric and behavioral abnormalities have also been documented. Individuals carrying 16p12.2 deletion do not present a common facial gestalt and do not share identical clinical presentation, which indicates that this microdeletion is nonsyndromic.

Most genomic disorders are the result of a non-allelic homologous recombination (NAHR) between large (larger than 10kb) and highly similar sequences, called segmental duplications. Several chromosomes are enriched in these types of DNA sequences, such as chromosome 16, most particularly its short arm. This leads to a higher frequency of this rearrangements and therefore, genomic disorders associated with this deletion/duplication.

16p12.2 microdeletion expands approximately 500kb, leading to a hemizygous state of six genes: UQCRC, C15orf65, VWA3A, EEF2K, POLR3E, CDR2 (Figure right). 16p12.2 microdeletion can be diagnosed by Fluorescent In Situ Hybridization (FISH) and Array Comparative Genomic Hybridization (array CGH). This molecular alteration cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic techniques

Assessing family history is essential in 16p12.2 microdeletion. In stark contrast to other syndromic disorders where most CNVs are de novo, this deletion was inherited from a parent in 95% of the cases.