Significant progress has been made in the effort to identify the biological foundations of human intelligence.  As is the case in many such endeavors, these achievements have not come from studies of intelligence itself, but rather largely from investigations into the causes of intellectual impairment.  Cognitive impairment can range from more focal difficulties, such as a specific deficit in reading ability (i.e. dyslexia) to broader learning dysfunction that may impact several functions (e.g. borderline IQ with attention deficit disorder) to diffuse disability that renders the individuals incapable of self-care or independent living as in the case of profound mental retardation (MR). 

MR is one of the most common causes of developmental disability in humans. One characteristic of the epidemiology of MR that has served to direct studies of the biological substrates of human intelligence is the excess of males who are diagnosed with MR. There is an approximate 30% excess of males with MR compared to females.  In fact, males tend to demonstrate increased vulnerability to a host of neurological syndromes.  Males outnumber females up to 4:1 in receiving a diagnosis of autism, show increased cognitive deficits and neuroanatomic abnormality following preterm birth and frequently demonstrate greater severity of impairment compared to females with the same diagnosis. 

The excess of males with cognitive deficits, particularly with MR, lead investigators to question the role of the X-chromosome in human cognition. There is some uncertainty as to the percentage of MR in males accounted for by XLMR, with estimates ranging from <10% to 23%.  However, genetic mapping studies continue to provide increasing information regarding the role of the X-chromosome in MR. During the past several years, 45 genes responsible for MR have been identified on the X-chromosome and cloned.  An additional 107 genes have been mapped but not yet cloned.  These numbers increase rapidly and updates are available online at http://www.ggc.org/xlmr_update.htm and http://xlmr.interfree.it/home.htm. 

Our XLMR project involves rare genetic syndromes affecting intellectual function. In collaboration with Greenwood Genetic Center in South Carolina, we have obtained volumetric MRI data for individuals with Coffin-Lowry, Snyder-Robinson, craniofacialskeletal, Renpenning and Allan-Herndon-Dudley syndromes, among others.  These studies provide unique information regarding the role of certain X chromosome genes such as RSK2, JARID1C, SMS and MCT8 in neurodevelopment and cognitive function.