Historical perspective

The field of behavioural phenotypes is concerned with determining the strength and nature of associations between genetic syndromes and behaviours including cognitive, motor, linguistic and social difficulties (O'Brien & Yule, 1995a).

The notion that genetic factors can influence the development, behaviour, and cognition of individuals has been in existence for over a century. Since the early 1930s a distinction has been made between individuals with severe and those with mild learning disabilities (Burack, 1990; Lewis, 1933; Penrose, 1963; Zigler, 1967). Those with mild learning disabilities were thought to represent the lower end of a continuous distribution of intellectual ability within the general population. Whereas those with severe learning disabilities were thought to have an organic cause for their difficulties (Roberts, 1952). The differentiation between organic and non-organic causes of learning disability has stood the test of time although it is now known that there are individuals with mild learning disabilities who have a pathological cause for their difficulties. For example, there are individuals with Fragile-X Syndrome with mild learning disabilities (Sabaratnam, Laver, Bulter, & Pembrey, 1994). Similarly, there are individuals with severe learning disabilities who do not have an identified medical condition (Herbst & Baird,

1982).

Most approaches to research in the last century have focused on either biological or environmental effects to explain individual differences in behaviour and cognition (see O'Brien and Yule, (1995a) for a review of the different approaches). For many years, the notion that behaviour was determined primarily by experience was widely accepted (e.g., Goldfarb, 1944; Spitz, 1945) and genetic factors were not considered important in aetiological models of behaviour. Consequently, the behaviour of individuals with learning disabilities was studied by grouping them according to ability level (i.e., mild, moderate, severe and profound learning disability) and individuals with different aetiologies were studied within the same subject group (e.g., Bihm, Poindexter, & Warren, 1998; Epstein, Cullinan, & Bursuck, 1985; Harris, 1993; Kumar, Mohanty, & Mohapatra, 1992). Despite this trend, there were still those who acknowledged the potential role of genetics on behaviour. For example. Down (1866) described individuals with a syndrome that would later bear his name as “They are humorous and a lively sense of

the ridiculous often colours their mimicry” (quote taken from Flint & Yule, 1994, p.4).

The field of behavioural phenotypes has only recently come into being. The field has developed slowly over the last 15 years from two different, but related, types of investigations. First, the new genetic techniques developed over the last 15 years have led to the identification of many genetic disorders. Once a genetic disorder has been identified, it is then possible to study individuals with that genetic anomaly to determine the extent to which they show the same behavioural features. It was this type of investigation that led to the first use of the term behavioural phenotype by Nyhan (1972) in his presidential address to the Society for the Study of Pediatric Research.

Lesch-Nyhan syndrome was first described in 1964 as an X-linked recessive disorder of purine metabolism (Lesch & Nyhan, 1964). In 1972, Nyhan proposed an association between the error in purine metabolism and the self-injurious behaviour seen in individuals with the syndrome (Nyhan, 1972). Findings of associations between other genetic anomalies and behaviour led to increased interest in this area.

The second way in which the field of behavioural phenotypes developed has been through the identification of a specific profile of behaviour in a group of individuals for which there is no biologically distinct syndrome. Genetic techniques then allow for the investigation of genetic anomalies that may underlie the specific behavioural profile. It was this type of investigation that led to the discovery of the genetic basis for Prader-Willi syndrome.

The syndrome was first described by Prader et al. in 1956 (Prader, Labhart, & Willi, 1956). In the 1980’s a number of studies were conducted in order to systematically characterise the features associated with Prader-Willi syndrome (e.g., Bray et al., 1983; Hurley & Sovner, 1984; Laurance, Brito, & Wilkinson, 1981; Vela Bueno et al., 1984). At that time, the genetic basis for the syndrome was unknown. These studies reported variability in the extent

and severity of the clinical features which lead to speculation that the syndrome may be aetiologically heterogeneous. In 1986, Butler, Meaney and Palmer reported a deletion in chromosome 15 in 21 of 39 cases and an abnormal karyotype in the other cases. Examination of other cases by different groups resulted in the finding that between 70% and 80% of cases with Prader-Willi syndrome have a deletion of 15q11-q13 of paternal origin (Ledbetter, Greenberg, Holm, & Cassidy, 1987). Groups studying the cases where no deletion was present have found uniparental disomy of chromosome 15 in a number of cases leading to the absence of paternal genetic material from the 15q11-q13 region (e.g. Robinson et al., 1991). In Prader-Willi syndrome the characterisation of the behavioural phenotype commenced prior to the identification of the genetic anomaly involved. Knowledge of the underlying genotype has led to further work on the characterisation of the behavioural phenotype. For example, in a recent study Roof et al. (2000) assessed the intellectual abilities of 24 individuals with Prader-Willi syndrome with a 15q11-q13 deletion and 14 individuals with Prader-Willi syndrome with uniparental disomy of chromosome 15. Those with a deletion had, on average, significantly lower IQ scores.

In these ways, the field of behavioural phenotypes has grown. Over 1000 genetically determined syndromes have been identified to date (Moser, 1992) and there has been increasing interest in profiling the behavioural features associated with these different genetic syndromes. There are a significant number of studies describing the cognitive and behavioural profiles associated with Lesch-Nyhan syndrome, Fragile-X, Angelman and Prader-Willi syndromes. Turner Syndrome, Smith Magenis Syndrome, Tuberous Sclerosis and Williams Syndrome, to name but a few.

With the explosion of gene-behaviour research, the term behavioural phenotype has come into regular use. However, there has been a tendency for researchers to overuse this term to describe any behaviour that has an association with a particular genetic disorder (Einfeld & Hall, 1994). It is

important to be certain about just what is meant by the term behavioural phenotype.