Copy Number Variation in Syndromic Forms of Psychiatric Illness: The Emerging Value of Clinical Genetic Testing in Psychiatry.

“Mr. A” is a 22-year-old man with a slim appearance who resides with his parents and works in their convenience store. For the past 2 years, he has been in a romantic relationship with a woman who lives independently nearby. Mr. A experienced his first psychotic episode at the age of 17, during which he was hospitalized for 6 weeks and treated with 5 mg/day of haloperidol, leading to a significant reduction in his psychotic symptoms.Mr. A was discharged with a diagnosis of psychotic disorder not otherwise specified, on maintenance treatment with haloperidol, andhebegan outpatient visitswith a psychiatrist. During the first year after his discharge from the hospital, Mr. A’s medication regimen was transitioned to 4 mg/day of risperidone because of extrapyramidal side effects on haloperidol, and his diagnosis was revised to schizophrenia. Since then, Mr. A has experienced several periods of increased psychotic symptoms. However, these were well controlled by transient increases of his risperidone dosage. During outpatient family meetings with Mr. A and his parents, it became apparent that Mr. A’s mother suffered from intermittent nonaffectivepsychotic episodes,which had never been formally evaluated or treated. The family agreed thatMr. A bore a close resemblance to hismother, both inpsychiatric symptoms and inphysical appearance. Mr. A’s mother also reported having a younger sister whom she described as “a little odd. ” Throughout elementary school, Mr. A’s performance was below average, and he was late in reaching developmental milestones. His elementary school teacher suggested to his parents that he may suffer from attention deficit hyperactivity disorder, but this was never formally evaluated. In secondary school, Mr. A continued to struggle academically and decided to stop attending school beyond the legal requirement at age 16. During the course of his outpatient treatment, neuropsychological testing revealed that Mr. A had substantial impairments in both attention and workingmemory. His full-scale IQwas determined to be 70, with a verbal IQ of 68 and a performance IQ of 72. Coincidentally, the family read an article in their local newspaper about genetic testing in patients with autism spectrum disorder, which prompted Mr. A to discuss genetic testing with his psychiatrist, who referred him for clinical genetic counseling. During thephysicalexaminationbytheclinicalgeneticist, Mr. A was noted to have dysmorphic facial features, including elongated face with low-set ears, elongated fingers and toes, and aflat nasal bridge. Oral examination revealed a high-arched palate. Genotyping of Mr. A and his parents revealed a maternally inherited 16p11.2 duplication. Brain MRI was notable for cavum septum pellucidum and enlargement of the third and fourth ventricles. The psychiatric symptoms and dysmorphic features of Mr. A and his mother are consistent with the 16p11.2 microduplication syndrome (OMIM #614671). The genetic counselor discussed with Mr. A and his parents the findings and the implications for future offspring. BothMr. A andhis parents reported that theywere comforted to learn that there was an identifiable cause of continued