BALTIMORE – Identifying shared endophenotypes might help clinicians characterize neurobehavioral syndromes and plan treatment, said a specialist in neurobehavioral development.
An endophenotype is a subset of features of a syndrome that are more highly correlated with a genetic mechanism than the whole syndrome, and grouping syndromes that share common features can help target and simplify treatment strategies, said Travis Thompson, Ph.D., also a professor in the department of pediatrics at the University of Minnesota, Minneapolis.
Some genetic evidence suggests that there might be shared inherited traits between autism and Prader-Willi syndrome (PW), and Dr. Thompson presented important behavioral similarities and differences between these two conditions at a meeting on developmental disabilities sponsored by Johns Hopkins University.
“Identifying clinically relevant endophenotypes can be more helpful than trying to figure out exactly which genes cause autism,” he said.
Phenotypic features that differ might be just as informative as those that are the same in understanding genetic and associated brain differences in clinical syndromes, Dr. Thompson said. “The fact that they are alike in some ways but different in a specific way tells you that there is probably a different genetic mechanism,” he said.
Candidates for a common genetic lesion include the γ-aminobutyric acid (GABA) receptor 3 (GABRB3), which might be absent or reduced in children with either autism or PW. And research has shown that both conditions might be associated with genes in the 15q11-q13 region of chromosome 15.
Features that are common to both autism and PW include compulsive behavior, social processing deficits (including facial processing deficits), and self-injury, Dr. Thompson said.
Compulsive behavior in children with either condition might be associated with overactive dopamine due in part to the missing or suppressed GABA-3 receptor. But some differences emerge within these categories. For example, compulsive behavior in children with PW often involves excessive overeating, which might be due to an overproduction of GABA. And skin picking is a common compulsive behavior in children with either condition, although in PW skin picking can start as early as 2 years of age, he said.
Studies have shown that face perception is limited in children with either autism or PW. This problem might be linked to a common genetic defect that might cause hypoactivation of the amygdala and fusiform face area–parts of the brain that recognize facial features.
More research is needed on common behavior phenotypes in neurobehavioral syndromes to determine which individuals show the maximum improvement to different treatments, and what characteristics of those individuals make them responsive to a specific intervention, he added. “That has to be the future of research in this area.”