Mental Retardation: Genetic Findings, Clinical Implications and Research Agenda

Abstract

The most important genetic advances in the field of mental retardation include the discovery of the novel genetic mechanism responsible for the Fragile X syndrome, and the imprinting involved in the Prader-Willi and Angelman syndromes, but there have also been advances in our understanding of the pathogenesis of Down syndrome and phenylketonuria. Genetic defects (both single gene Mendelizing disorders and cytogenetic abnormalities) are involved in a substantial proportion of cases of mild as well as severe mental retardation, indicating that the previous equating of severe mental retardation with pathology, and of mild retardation with normal variation, is a misleading over-simplication. Within the group in which no pathological cause can be detected, behaviour genetic studies indicate that genetic influences are important, but that their interplay with environmental factors, which are also important, is at present poorly understood. Research into the joint action of genetic and environmental influences in this group will be an important research area in the future.

Short Normal Children and Environmental Disadvantage: A Longitudinal Study of Growth and Cognitive Development from 4 to 11 Years

“…Simonoff, Bolton, and Rutter (1996) have hypothesised that genetic factors contribute substantially to persistent mild mental handicap, whether or not this is associated with language problems. The design of our study unfortunately does not allow us to test this hypothesis directly, but several strands of evidence suggest that the picture is a complex one.…”

Specific Genetic Disorders and Autism: Clinical Contribution Towards their Identification

“…The construction of the pedigree may suggest a possible way that heredity plays a role and can allow for discussion of specific hypotheses. The clinician should search for consanguineous mating, for other affected relatives, for medical and psychiatric family history, learning and developmental difficulties, deceased infants, and malformations (Ponsot, Moutard & Villeneuve, 1998;Simonoff, Bolton, & Rutter, 1996). Of note, spontaneous abortions are rarely evoked but their repetition is a strong argument for a familial chromosomal anormality.…”

“…Skin should be examined with Wood lamp when there is doubt to confirm tuberous sclerosis (He´ron, 1999;Simonoff et al, 1996). Specific signs of autism should be assessed, and subtype and severity determined.…”

The Schizophrenia Phenotype in 22q11 Deletion Syndrome

“…Several authors (28)(29)(30) have made a case for considering subjects with mild mental retardation and schizophrenia to have a neurodevelopmental form of schizophrenia with similar symptom profiles and courses as schizophrenia in the general population. We therefore compared the symptom severity scale scores and age at onset of the eight 22qDS-schizophrenia patients with mild mental retardation and the 16 22qDS-schizophrenia patients without mental retardation.…”