Down syndrome cell adhesion molecule, DSCAM, also known as CHD2, is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs). DSCAM is classified as a type I membrane protein with an extracellular domain consisting of ten immunoglobulin (Ig) and six fibronectin type III (FNIII) repeats and an intracellular domain that does not contain any identifiable motifs.¹

The gene coding for the DSCAM protein is located on the human chromosome 21, specifically in the so-called Down syndrome critical region (DSCR), the trisomy of which is considered a determinant for the intellectual disability associated with Down’s syndrome. Therefore, the potential involvement of DSCAM in the developing neural system, has received considerable attention.^2,3

DSCAM is widely expressed in the vertebrate central nervous system where it plays a crucial role in neural development. DSCAM was found to have a critical role for the development of neural circuits, playing a role in processes such as axon guidance, dendritic arborization, and synapse formation. ^2-5

DSCAM is involved in axon guidance, a process by which developing neurons extend their axons to establish specific connections with target cells. DSCAM serves as a receptor for Netrin-1, a member of a conserved family of secreted proteins that promote axon outgrowth and guide growth cone navigation.^2,6

The molecular mechanisms by which DSCAM contributes to autism spectrum disorders (ASDs), is not clear, but it may involve altered synaptic transmission, probably through its interaction with other adhesion molecules such as neuroligins (NLGNs) and neurexin1 (NRXN1). In fact, deletion of DSCAM in neurons results in abnormal spine maturation, altered synaptic transmission, as well as autism-like behaviors.⁵