Abstract
The neurobiological consequences of trisomy 21 remain incompletely understood. Considered as a syndrome-complex of chromosomal (genetic) origin with multiple neurodevelopmental and neuropsychological manifestations it will be a very long time before a complete understanding of this condition emerges based upon molecular, genetic, and neurobiological principles. The construct of Down syndrome (DS) as a developmental disorder is, by itself, incomplete and most unsatisfactory based upon emerging biological concepts. However discussions of DS as a developmental disorder characterized primarily by developmental delay, does permit highly complex biological events to be easily conceptualized in terms of the whole child. Our current models of child development and the interventions designed to support neuromaturation in young children with DS will require further integration with emerging genetic, neurobiological, neuropsychological, and pharmacological paradigms. A cogent framework for successful pharmacological treatment of certain aspects of cognitive and behavioral dysfunction is beginning to emerge. At the same time, a growing number of untested, nutrition- and development-based therapies are continually offered to the families of young children. The need for well-designed studies to measure the effects of early, focused clinical intervention of any kind is obvious. Our ability to competently serve young children with DS will advance once a commitment to clinical trials is recognized and acted upon.
DOWN SYNDROME (DS) is a chromosomal disorder that occurs in approximately 1 in 800 to 1000 live births. Chromosome 21, the smallest human autosome, contains 33.8 million base pairs of DNA and is predicted to contain just 225 genes, many or all of which contribute to the pathogenesis and phenotype of DS (Hattori et al., 2000; National Center for Biotechnology Information [NCBI], 2002) One hundred and thirty-eight years ago John Langdon Down, an Englishman, published the first clinical description of the condition that now bears his name. Throughout this century distinct genetic, neurobiological, psychological, developmental, and medical models of DS have evolved, each having its own set of principles, practices, and pedagogy resulting in distinctly separate definitions of reality among basic scientists, health care practioners, development-based therapists, and parents and an astounding array of treatment options, both real and imagined. DS may be best understood as a syndrome-complex of genetic origin with protean neurobiological consequences, and several characteristic neurodevelopmental and neuropsychological manifestations (Carr, 1988; Coyle, Oster-Granite, & Gearhart, 1986; Wisniewski, 1990). Presently, there are no biomedicine-based treatments for the central nervous system (CNS) impairment specific to children with this condition.
It is becoming acceptable in some academic circles to entertain discussions regarding the heritability of human intelligence, or more important some determination regarding the relative contribution of genetic, epigenetic, and early environmental factors upon measures of cognitive ability. Twin studies continue to offer the most remarkable insights into genomic and environmental contributions to cognitive function as measured by several indicators. Current estimates are that 40% to 70% of the variance in measured intelligence observed in these study populations can be explained by inherited genetic factors, 20% by maternal effects, and 4% by parental education (Boomsma, van Baal, & Caroline, 1998; Bouchard, Lykken, McGue, Seagle, & Tellegen, 1990; Devlin, Daniels, & Roeder, 1997; Pal, Shyam, & Singh, 1997; Scarr & Weinberg, 1983). It is also recognized that a surprisingly high proportion of functional brain anatomy and corresponding verbal intelligence is under direct genetic or epigenetic control (Thompson, van Erp, & Poutanen, 2001). These findings are critical to furthering our understanding of the linkage between genes, speech, language, memory, and cognitive function. Efforts to understand the basis for inherited genetic predisposition and the manner in which overexpression of genes on chromosome 21 specifically alter that predisposition should yield new and particularly exciting insights into our understanding of neurolinguistic and neurocognitive dysfunction in DS.