Autism and Fragile X: Differences and Intersections

Considering autism and Fragile X Syndrome (FXS) together highlights the complexity of genetic and neural networks in autism as well as pointing to the usefulness—indeed, the benefits—-of studying autism in comparison to other conditions. Fragile X Syndrome and autism at the intersection of genetic and neural networks by Matthew K. Belmonte of the Department of Human Development at Cornell University and Thomas Bougeron of the Laboratoire de Génétique Humaine et Fonctions Cognitives, Institute Pasteur, note that autism is an “entirely behavioral diagnosis,” while FXS “is caused by the silencing of a single gene (FMR1) that codes for the fragile X mental retardation protein (FMRP)” and can be identified by a “specific biomarker.” While the prevalence is 4% or less for cases of autism associated with FXS, the prevalence of autism in FXS ranges from 5% to 60%. Belmonte and Bougeron note that recent studies using “comprehensive diagnostic instruments” have found “prevalence estimates for autism in the FXS population between 18% and 33%. They further note that:

…. the heterogeneity of neuropathological and genetic observations in autism suggests that autism’s essential characteristic may not be any specific cellular pathology, but rather a perturbation of the network properties that emerge when neurons interact. Thus even though FXS and autism differ starkly at the level of single-gene dysfunction, they may bear a great deal of similarity in terms of network dysfunctions and the combinational effects of genetic, epigenetic and environmental modifying factors on these network dysfunctions. Disorders whose analyses can be confined within single genes or isolated cells are, comparatively speaking, easy to understand. Network problems are hard, but solving them promises profound insights into learning and memory and the development of cognition.

Studies of developmental disorders whose approach has been to “attempt to dissect developmental disorders as though they were lesions, a missing locus or capacity in an otherwise normal, fully developed brain” are “inappropriate” because of the assumption that a developmental disorder is “localized module, rather than an emergent property of developmental interactions among many brain regions and functions.” Belmonte and Bougeron thus point out the importance of studying “networks of interacting genes and networks of interacting neurons” to understand the complexity of autism, which they describing as having “multiple causal factors.” Autism, they posit, may arise from various combinations of “cumulative and overlapping factors”:

1. An anomaly in synapse formation or maintenance (which could have no consequences or be associated with isolated mental retardation)
2. An imbalance between excitation and inhibition which could have no consequences or be associated with epilepsy)
3. Abnormal cell number (which could be associated with macro- or microcephaly)
4. Abnormal neuromodulatory function affecting network properties (which could have no consequences or be associated with obsessive-compulsive disorder or other neuropsychiatric diseases)

Go here to read Fragile X Syndrome and autism at the intersection of genetic and neural networks.