|| Bioinfo Publications || 99 MOLECULAR GENETICS OF INTELLECTUAL DISABILITY WITH SPECIAL EMPHASIS ON THE IDIOPATHIC TYPE DAS A.B. 1 AND MUKHOPADHYAY K. 2 * 1 Centre for DNA Fingerprinting and Diagnostics, Diagnostics Lab, 4-1-714, Tuljaguda Complex, Nampally, Hyderabad- 500001, AP, India. 2 Manovikas Biomedical Research and Diagnostic Centre, Kolkata-700107, WB, India. *Corresponding Author: Email- drkanchanm@gmail.com Received: April 04, 2012; Accepted: September 10, 2012 Abstract- Intellectual disability (ID), a phenomenon characterized by significantly subaverage intellectual functioning with deficits in adap- tive behavior, such as daily-living skills, social skills and communication, is of common occurrence throughout the world. Depending on the diagnostic methods used, 2-85 individuals per 1000 are diagnosed with ID. Extraordinarily heterogeneous causes like environmental, chro- mosomal and/or genetic defects have been found to be associated with ID. Among these, genetic abnormalities are frequently encoun- tered in connection with ID and therefore, unraveling the genetic causes of ID is one of the greatest challenges for molecular geneticists. Recent advances in high resolution comparative genomic hybridization and annotation of genomic sequence have helped in identifying cryptic changes and different syndromes not known earlier. Further, several novel X-linked and autosomal genes, that may lead to ID, have been identified by molecular genetic approaches and the process is still going on. In this review, an attempt has been made to com- pile recent advances in the molecular genetics of ID and in discovering new genetic conditions that may give rise to nonsyndromic ID or idiopathic ID (IID). From the evidences obtained, genetics of IID turned out to be remarkably complex. It may be inferred that the molecular mechanism behind IID is far from understanding till date and is likely to remain a challenge for clinicians and scientists for years to come. Key words- intellectual disability, nonsyndromic, idiopathic, genetics Introduction Intellectual Disability (ID), the most common form of cognitive im- pairment, is a circumstance, a reality, a symptom, a source of pain and incomprehension to many families. The American Association of Intellectual and Developmental Disability (AAIDD; earlier known as AAMR) defines ID as a disability characterized by significant limitations both in intellectual functioning and adaptive behavior, which covers day to day social and practical skills, originating be- fore the age of 18 [1]. This definition is widely accepted and em- phasizes on social and environmental effects rather than the state of the individual. The term “ID” (more frequently defined as mental retardation or MR) is highly controversial; arguments mainly deal with conceptual approaches as well as phenotypes associated with the disorder. Based on the traditional approaches, which mainly define the basis of medical or statistical model of definition, ID is considered as a state of a person with limitations in adaptive and communication skills. Characteristic symptoms are identified by the medical model, while the statistical model mainly categorizes by the intelligence quotient (IQ) of an individual [2]. Since there is no standardized method for determination of social adaptive behavior under differ- ent socioeconomic and cultural environments, IQ forms the sole criterion for classifying ID rather than adaptive behavior [2]. On the basis of IQ, the Diagnostic and Statistical Manual for Mental Disor- ders-IV-TR (DSM-IV-TR) [3] categorizes five different levels of ID: borderline (IQ 67-83), mild (IQ 50-66), moderate (IQ 33-49), severe (IQ 16-32), and profound (IQ<16). Due to concern about the over or misidentification of ID, particularly in minority populations, bor- derline classification was eliminated from the interpretation of sig- nificant, subaverage, general intellectual functioning and the upper range of IQ was changed from <85 to < 70-75. On the bases of presenting symptoms, ID can be grouped into two major subclasses i.e. syndromic (S) and non-syndromic (NS) [4]. Syndromic ID cases are characterized by certain definite clinical, radiological, metabolic or biological features while in NS-ID, cogni- tive impairment is the major manifestation. However, it has been a challenge to rule out the presence of neurological anomalies and psychiatric disorders in these patients, as they may be less appar- Citation: Das A.B. and Mukhopadhyay K. (2012) Molecular Genetics of Intellectual Disability with Special Emphasis on the Idiopathic Type. International Journal of Genetics, ISSN: 0975-2862 & E-ISSN: 0975-9158, Volume 4, Issue 3, pp.-99-110. Copyright: Copyright©2012 Das A.B. and Mukhopadhyay K. This is an open-access article distributed under the terms of the Creative Com- mons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. International Journal of Genetics ISSN: 0975-2862 & E-ISSN: 0975-9158, Volume 4, Issue 3, 2012 International Journal of Genetics ISSN: 0975-2862 & E-ISSN: 0975-9158, Volume 4, Issue 3, 2012, pp.-99-110. Available online at http://www.bioinfo.in/contents.php?id=25