atural resolution or the underlying factor in the diagnostic misattribution.
Onset during the developmental period
The developmental period is most often defined as between birth and age 18. Although useful for legal and guardianship purposes, this legalistic cutoff is inconsistent with current models of neurodevelopment. Research suggests that brain maturation and neuroplasticity continue well past age 18. For individuals with IDD, ongoing brain development suggests a lifelong capacity for skill learning, provided the individual is free of neurodegenerative, neuropsychiatric or medical illnesses. But there is a paradox inherent to this observation. The timing of any insult on brain development is complex and incompletely understood. There are fundamental neurobiological differences between acquired lesions in adulthood and those occurring during critical periods in brain development. Even though some insults during infancy are more amenable to interventions, there may still be potential limits imposed on later developing neurocognitive skills. The critical piece is the timing of the intervention: early and intensive intervention during periods of rapid brain development is most effective for many but not all areas of development.
Many genetic syndromes present another twist: the age of onset is often inversely related to the severity, clinical course and prognosis. Milder forms of autosomal disorders present with minimal findings during childhood but then emerge and slowly progress during adolescence or early adulthood. Classification based on a cutoff age of 18 becomes confusing when there is a very slow cognitive decline (drop in IQ score and decreasing adaptive skills) that is finally recognized in late adolescence. This scenario is more consistent with neurodegenerative or dementing illness that was masked by learning disability or low normal intelligence until clear cut neurological or metabolic symptoms emerged. Both traumatic brain injury and the onset of neurodegenerative disorders during late adolescence may contribute to behavioral or mental health problems prior to obvious cognitive decline. This gap can make it more difficult to determine the age of onset issue.
Genes and developmental disabilities
The number of genetic syndromes is growing in conjunction with the development of new genetic techniques. 30 years ago genetic testing usually meant chromosome testing and linkage studies. Nowadays we can obtain genome wide scans, florescence in situ hybridization, and microarrays that hone in on single nucleotide polymorphisms, copy number variants and the structure of specific genes (18). Recent breakthroughs in Fragile X research have opened another doorway with the discovery that mglut5 antagonists appear to reverse both molecular and cognitive/behavioral features of Fragile X (18, 19). There is growing research in epigenetics that point to changes in genes regulation due to trauma or faulty parenting. These findings challenge genetic determinism and force us to rethink nature-nurture arguments in terms of a newer understanding of gene–environment interactions.
Behavioral phenotypes are patterns of cognition and behavior associated with specific genetic disorders. Examples include: gaze aversion and anxiety in Fragile X (20); hyperphagia and binge eating in Prader Willi syndrome (21); personality traits linked to Trisomy 21 (22); increased risk for schizophrenia in 22q deletion (Velocardiofacial syndrome) (23); and epilepsy, dysmorphologies, hypotonia, and autism in 15q11.2-13 duplications (24). Many behavioral phenotypes bear some resemblance to temperamental features of affected individuals. Others seem more like prodromal primary psychiatric disorders (18). Unfortunately, there are too many genetic and neuroanatomical “smoking guns” for polygenic disorders like psychosis, bipolar disorder/schizophrenia, autism, and epilepsy in patients with IDD. This observation suggests that we are dealing with complex disorders and reinforces the idea that many syndromes are related to disruptions in pathways rather than 