How do genetic tests answer questions about neurodevelopmental differences? A sociological take.

When it comes to neurodevelopmental differences, a genetic test result can provide compelling answers. However, it is not always clear what the relevant question is. If we want to understand the impact of a genetic diagnosis such as NGLY1 deficiency or the fragile X, trisomy X, or 22q11.2 deletion syndromes on people with neurodevelopmental differences, we must be mindful about what exactly a genetic test is supposed to tell us, where and for whom it matters, and which avenues for action it opens or forecloses. These are all moving targets. Specifically, I discuss the shifting ways a genetic test result can answer the following questions. What is this person's diagnosis? What symptoms and developmental differences are they likely to experience? What is the best way to approach their development, treatment, and care? Will they have a life worth living? When you unpack the sociological nuances of each question, the history behind them, and the uneven ways they are asked, the meanings of the answers change quite radically. I discuss the implications for social inequalities and urge experts and stakeholders to exercise agency when they interpret a genetic diagnosis. WHAT THIS PAPER ADDS: The questions a genetic test can answer depend on a range of social factors. Whether and how a genetic test result affects diagnosis, identity, prognosis, and treatment is a moving target. Genetics creates questions about a life worth living that it cannot answer alone. Stakeholders must choose the questions about neurodevelopmental differences that genetics should answer.

Looping Genomes: Diagnostic Change and the Genetic Makeup of the Autism Population.

This article builds on Hacking's framework of "dynamic nominalism" to show how knowledge about biological etiology can interact with the "kinds of people" delineated by diagnostic categories in ways that "loop" or modify both over time. The authors use historical materials to show how "geneticization" played a crucial role in binding together autism as a biosocial community and how evidence from genetics research later made an important contribution to the diagnostic expansion of autism. In the second part of the article, the authors draw on quantitative and qualitative analyses of autism rates over time in several rare conditions that are delineated strictly according to genomic mutations in order to demonstrate that these changes in diagnostic practice helped to both increase autism's prevalence and create its enormous genetic heterogeneity. Thus, a looping process that began with geneticization and involved the social effects of genetics research itself transformed the autism population and its genetic makeup.

The chromosome 22q11.2 deletion: from the unification of biomedical fields to a new kind of genetic condition.

How can genetics reshape nosology? This paper examines the way knowledge about a genetic mutation - the microdeletion at chromosomal locus 22q11.2 - transformed our understanding of several rare clinical syndromes and designated a qualitatively new population of patients. Taking the 1400 papers about the 22q11.2 deletion and the clinical conditions with which it was associated, we generate a network of papers tied by citations for each of the last 35 years. Using a modularity algorithm, we identify communities and evaluate their salience for the networks' overall structure. This analysis, supplemented by historical research and fieldwork with relevant experts and the advocates of affected children conducted during 2011-12, reveals that the 22q11.2 deletion acted as a 'boundary object' that unified clinical literatures and led to the emergence of a new kind of medical condition: 22q11.2 Deletion Syndrome (DS). The case of 22q11.2DS extends our understanding of 'genomic designation' - the delineation and diagnosis of clinically diffuse conditions according to characteristics of the genome - and demonstrates that observations from genetics can reconfigure existing categories of biomedical research and lead to the emergence of qualitatively new diagnostic categories.

Genetic counseling, activism and 'genotype-first' diagnosis of developmental disorders.

This paper presents a sociological examination of the role of genetic counselors as advocates, not only for patients and their families, but also for genetic conditions themselves. In becoming activists for new disorders, genetic counselors are helping to create new categories that will shape expectations and treatment regimens for both existing patients and those who are yet to be diagnosed. By virtue of their expertise and their position at the intersection of several key professions and constituencies, genetic counselors are likely to play a central role in the way the genetic testing technologies, and especially 'genotype-first' diagnosis, impacts the way we understand and categorize developmental difference. I outline some of the promises and dangers that this kind of activism holds for people with developmental disabilities, and particularly the challenge presented by systemic ascertainment bias in the face of genotype-phenotype uncertainty. I argue that new testing techniques like microarray analysis that do not need to be targeted on the basis of clinical presentation throw these challenges into sharp relief, and that the genetic counseling community should consider how to marry advocacy for new genetic conditions with an emphasis on the indeterminate developmental potential of every child.

Genomic designation: how genetics can delineate new, phenotypically diffuse medical categories.

This paper reports and discusses 'genomic designation' as a way of classifying people. In genomic designation the object of biomedical analysis--and the concomitant medical category that is subject to scientific, clinical, and social action--is delineated on a genomic basis, while the phenotype is decentralized and tabulated post factum. Unlike prominent sociological concepts such as biosociality or geneticization, where genetic proclivities for or explanations of phenotypic categories affect social processes, genomic designation treats characteristics of the genome as the essential referent of new categories of illness. I outline the relevant sociological literature and the shift to what Nikolas Rose has called the 'molecular gaze' before explicating the concept ofgenomic designation and its half-century history. I use 22q13 Deletion/Phelan-McDermid syndrome as an example of genomic designation: investigations into the deletion of genetic material at site q13 on the 22nd chromosome preceded and made practicable the delineation of a syndrome more than a decade later, even though the associated phenotype is not distinct enough for diagnosis. Finally, I discuss the implications of this turn to 'rigidly designate' kinds of people according to observations made at the level of the genome and outline directions for future research.