Overview of Intellectual Disability (ID)

/Overview of Intellectual Disability (ID)
Overview of Intellectual Disability (ID)2017-01-06T22:14:29+00:00

Intellectual Disability (ID) disorders or syndromes (formerly known as mental retardation) affect about 1% to 3% of the western population; in the U.S. alone, this would represent up to almost 10 million people.  ID is defined as an IQ score below 70 and is associated with many different disorders.  Thus far, deletions or mutations in more than 400 different genes (ID genes) have been shown to cause ID.  Historically, conceptualizing therapeutic treatments (i.e. drugs) for ID disorders has been difficult because of the vast number of unique genes involved and the non-uniform nature of the patient phenotype (phenotype refers to a patient’s observable characteristics and traits).

However, it is now believed that a number of the 400-plus genes that cause ID can be sub-grouped because of a potentially common molecular etiology (or cause).  This raises the possibility that certain groups of ID patients can be targeted with a common approach to drug treatment.

Overview: We have identified two sub-groups of ID disorders whereby it may be possible to target patients via a common approach to drug development:

  • Epigenetic machinery-related
  • Autism Spectrum Disorder-related

Click on the corresponding tabs to learn more about each of these two sub-groups. In some cases, the two sub-groups above may overlap with patients falling within both characterizations. It is also important to note that other ID disorder sub-groups may continue to arise through scientific understanding.

Epigenetic machinery-related: ID disorders that result from deletions or mutations in genes encoding or interacting with components of the epigenetic machinery (these syndromes often also share phenotypic overlap which may include developmental delays and other congenital anomalies). Epigenetics refers to changes in gene expression that do not involve changes to the underlying DNA sequence – a change in phenotype without a change in genotype – and involves the study of chemical reactions that activate and deactivate parts of the genome at different times and locations (i.e. turning genes on or off). Epigenetic modifications play a major role in gene expression and other cellular processes, and ultimately, in the regulation of cognition in several ID disorders such Kleefstra syndrome, Rett syndrome, Kabuki syndrome and Rubinstein-Taybi syndrome, to name a few. Therefore, the epigenetic modifications in the epigenetic machinery are an exciting area of focus for treating a vast number of ID syndromes. The role of epigenetics has been heavily studied in the field of cancer, the findings of which can be heavily applied to ID disorders.
Autism Spectrum Disorder-related: Autism is a spectrum disorder, defined by certain behaviours which come in combinations and in degrees of intensity that vary in each child and adult affected. ASD is the most common neurological condition diagnosed in children and, according to Autism Speaks, it is now estimated that 1 in 68 children will be diagnosed with ASD. There are over 100 genetically-linked disorders on the Autism Spectrum, with a significant percentage of them resulting in ID. Recent research demonstrates significant molecular convergence of these genetically-linked ASD disorders, suggesting a potential common approach to drug treatment.