The role of behavioral phenotyping in establishing a diagnosis of pseudo-angelman syndrome

Background: Behavioral phenotypes are observable patterns of behavior present in certain genetic syndromes that have distinctive social, linguistic, cognitive, and motor profiles. These may play an important role as pointers toward certain genetic disorders. The recognition of aberrant behavior is important for therapeutic targeting by behavioral modification strategies and medication. The repertoire of behavioral constellations is exhaustive, but common manifestations include aggression, self-injury, autistic features, and a happy demeanor comprising excessive smiling and outbursts of laughter without any preceding triggers. Clinical Description: We describe the approach that was used to establish diagnosis in a boy with a happy disposition, cognitive impairment, and seizures, the firstborn of a couple desiring genetic counseling for their second 7-week pregnancy. After deep phenotyping (identifying overt and concealed dysmorphism, assessment of vision, hearing, behavior, and cognition), a syndrome search was performed by a geneticist using suitable handles. The clinical phenotype of the proband was then matched with the generated list of disorders. The most likely diagnosis Angelman syndrome (AS) was excluded by negative specific genetic testing. Chromosomal microarray identified 2q23.1 microdeletion that is associated with pseudo-AS. Prenatal diagnosis at 16 weeks revealed an unaffected fetus. Management: There is no cure for this syndrome. Affected children benefit from symptomatic intervention provided by a multidisciplinary team including clinical geneticists, pediatricians, pediatric neurologists, developmental pediatricians, and various professional therapists. Conclusions: Behavioral phenotypes aid in establishing diagnosis in certain genetic disorders. A happy disposition coupled with intellectual disability should prompt the clinician to involve a geneticist in management, even if overt dysmorphism is not apparent.