The interdisciplinary quest for behavioral biomarkers pinpointing developmental disorders

To date, a large number of developmental disorders remain unrecognized until the child is of preschool age. In some cases the diagnosis is not made until even later in life. Such delays in diagnosis are not ideal. Early detection is desirable so that intervention can be provided to the child and support provided to the parents. The etiologies of the developmental disorders that often remain unrecognized until preschool or later, include (a) monogenetic disorders caused by mutations in a single gene (e.g. fragile X syndrome, FXS), (b) monogenetic disorders with genetic heterogeneity (e.g. Noonan syndrome), (c) genetically complex disorders (e.g. autism spectrum disorders, ASD), and (d) neurodevelopmental disorders with an unknown genetic etiology (e.g. non-syndromic intellectual disability). Common denominators of such disorders, irrespective of etiology, include delayed diagnosis, the (believed) absence of recognizable parameters that point to a certain disorder, and/or symptoms during the early stages of development that fail to raise sufficient suspicions of potential maldevelopment.

FXS, the most prevalent form of inherited intellectual disability and one of the known genetic conditions potentially associated with the ASD phenotypes [1], represents a good example. Most of its features are either not detected at an early stage or are not recognized as being associated with FXS. Indeed, the average age of diagnosis is in the preschool years [2]. This time lapse delays access to early intervention programmes, causes additional costs and frustration for families, and often impedes informed family planning. With respect to family planning related to having additional children, about 25% of families with a full-mutation male, and about 39% of families with a full-mutation female were reported to have another child with FXS [2].

FXS is just one example of a disorder that often remains undetected beyond toddlerhood. The same scenario is true for a number of other conditions and these conditions thus need to be studied in more detail to avoid diagnostic odysseys for the families, enable prospective studies and the provision of early intervention, facilitate the provision of parent support, and inform family planning.

A late diagnosis decreases the possibilities to study early development and thus hampers research on very young individuals with “late recognized conditions”. While a large number of studies have relied on retrospective parental questionnaires, there has been increasing doubt about the validity of these types of investigations. Retrospective video analysis (RVA) is considered a more objective approach that could help offset the potential bias and memory problems associated with retrospective parental questionnaires [3–8].

While there are also methodological difficulties with the use of RVA, including the very real issue of having limited access to data, several researchers have taken up the challenge of unraveling and describing “late recognized conditions” during the first years of life using this approach. Most research efforts have focused on the study of ASD, but there have also been studies on other genetic disorders (e.g. Rett syndrome, RTT; FXS) and other neurodevelopmental disabilities, such as developmental dyslexia, communication disorders, or specific language impairment, to name but a few. Because specific physical features associated with these conditions are not present or are commonly detected later in development, many research approaches have focused on associated neurobehavioral abnormalities and on detecting peculiarities in the child’s skills. Utilizing RVA essentially contributed to the understanding of the first 2 years of life in ASD and to a smaller extent also in RTT and FXS [4, 7–15]. The insights gained from this approach suggest that intensive research is needed to identify and understand the potential behavioral biomarkers that could pinpoint specific developmental disorders.

In facing this challenge together with the increasing need to integrate individual approaches in studying developmental phenomena, one should always keep in mind an obvious but sometimes forgotten issue: age-specificity. Every age-period has its specific window to differently assess the integrity of the central nervous system at the behavioral level. Some of these windows stay open for a while (e.g. vocabulary acquisition [16]), but other close rather rapidly (e.g. fidgety general movements [17]). Bearing in mind the dynamics and developmental changes of various developmental domains when delineating potential markers of maldevelopment, we expect to be able to unravel more and more mysteries of early development in due time. To reach this goal, we have to rely on carefully and thoroughly elaborated interdisciplinary approaches and the experts of different disciplines have to rely on one another to create a “same-language environment” that will likely increase the rate of success. We, as researchers, are still in transition, still on our way in crossing the borders of our disciplines [18] with the ultimate aim of being an expert in one, but familiar with all disciplines, thus creating a “new human developmental science”. Processes are required that will facilitate this crossing of interdisciplinary boarders so as to facilitate research that integrates the knowledge bases and the unique methods and techniques of the range of relevant disciplines that can contribute to the pinpointing of biomarkers for developmental disorders.

Declaration of interest

The authors have no conflicts of interests to report. The authors alone are responsible for the content and writing of this paper. Peter B. Marschik’s work on this manuscript was supported by the Austrian Science Fund (FWF P25241).