Copy number variation plays an important role in clinical epilepsy.

OBJECTIVE: To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. METHODS: We identified patients with International Classification of Diseases, ninth revision (ICD-9) codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children's Hospital. We reviewed medical records and included patients who met criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. RESULTS: Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1-4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18kb to 142Mb, and 34% were >500kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or "hotspots." We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. INTERPRETATION: Copy number abnormalities play an important role in patients with epilepsy. Because the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy.

Bullying and ADHD: Which Came First and Does it Matter?

CASE: Aiden, a 13-year-old boy in the sixth grade who is relatively new to your practice, is seen for follow-up after his routine physical last month when you noted concerns for possible attention-deficit hyperactivity disorder (ADHD) and gave the family Vanderbilt Scales to complete. Aiden has a family history of ADHD, specific learning disabilities, and mood disorder.His mother reports that she is concerned about how Aiden is doing at school; his teachers are complaining that he is not doing his work, and she is worried that he may be kept back in school. Aiden first began having trouble in the third grade. He was retained in the fourth grade for academic and behavioral reasons. Now his mother has been receiving calls about him not paying attention, distracting others, and staring at his paper. At home, he does not want to do homework and gets very frustrated. In fifth grade, he had a psychoeducational evaluation and was found not eligible for services. His achievement testing showed average scores in reading, math, and writing. Cognitive testing demonstrated average scores for verbal and nonverbal abilities and memory but was significantly below average for processing speed. Aiden continues to have problems now in into the sixth grade.You speak with Aiden in the office and ask him about school. He says, "It's bad. I'm failing." He believes his major problems at school are that he is not doing his homework, he easily becomes frustrated, and he argues with the teachers. He has supportive relationships with his family and friends at school. He gets along well with some of his teachers, noting that he loves his science teacher even though she is tough and "gives hard homework." He describes his history teacher as "annoying." When you ask what he means he states this teacher "Can be not nice and says mean things. She picks on me a lot." His description is consistent with the use of shaming as a behavior he experiences at school.You review the completed parent and teacher Vanderbilt forms; both are consistent and concerning for combined type ADHD. You discuss the diagnosis of ADHD with his mother and both agree to revisit pharmacotherapy in September when the school year resumes. You give her resources on ADHD and classroom accommodations and discuss requesting a 504 plan at school. You also discuss behavioral therapy to better address his self-regulation skills.A week later, you receive a telephone call from Aiden's mother. "Aiden got home today and he is more upset than I have ever seen him! His teacher told him in front of the class that he would probably stay back a year and now he is saying there is no point in going to school." She is not aware if retention has been recommended for Aiden.What would you say to Aiden's mother? What would you do next?

Bullying and ADHD: which came first and does it matter?

CASE: Aiden, a 13-year-old boy in the sixth grade who is relatively new to your practice, is seen for follow-up after his routine physical last month when you noted concerns for possible attention-deficit hyperactivity disorder (ADHD) and gave the family Vanderbilt Scales to complete. Aiden has a family history of ADHD, specific learning disabilities, and mood disorder.His mother reports that she is concerned about how Aiden is doing at school; his teachers are complaining that he is not doing his work, and she is worried that he may be kept back in school. Aiden first began having trouble in the third grade. He was retained in the fourth grade for academic and behavioral reasons. Now his mother has been receiving calls about him not paying attention, distracting others, and staring at his paper. At home, he does not want to do homework and gets very frustrated. In fifth grade, he had a psychoeducational evaluation and was found not eligible for services. His achievement testing showed average scores in reading, math, and writing. Cognitive testing demonstrated average scores for verbal and nonverbal abilities and memory but was significantly below average for processing speed. Aiden continues to have problems now in into the sixth grade.You speak with Aiden in the office and ask him about school. He says, "It's bad. I'm failing." He believes his major problems at school are that he is not doing his homework, he easily becomes frustrated, and he argues with the teachers. He has supportive relationships with his family and friends at school. He gets along well with some of his teachers, noting that he loves his science teacher even though she is tough and "gives hard homework." He describes his history teacher as "annoying." When you ask what he means he states this teacher "Can be not nice and says mean things. She picks on me a lot." His description is consistent with the use of shaming as a behavior he experiences at school.You review the completed parent and teacher Vanderbilt forms; both are consistent and concerning for combined type ADHD. You discuss the diagnosis of ADHD with his mother and both agree to revisit pharmacotherapy in September when the school year resumes. You give her resources on ADHD and classroom accommodations and discuss requesting a 504 plan at school. You also discuss behavioral therapy to better address his self-regulation skills.A week later, you receive a telephone call from Aiden's mother. "Aiden got home today and he is more upset than I have ever seen him! His teacher told him in front of the class that he would probably stay back a year and now he is saying there is no point in going to school." She is not aware if retention has been recommended for Aiden.What would you say to Aiden's mother? What would you do next?