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1. Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies

Author

Fountain, Michael D, Oleson, David S, Rech, Megan E, Segebrecht, Lara, Hunter, Jill V, McCarthy, John M, Lupo, Philip J, Holtgrewe, Manuel, Moran, Rocio, Rosenfeld, Jill A, Isidor, Bertrand, Le Caignec, Cédric, Saenz, Margarita S, Pedersen, Robert C, Morgan, Thomas M, Pfotenhauer, Jean P, Xia, Fan, Bi, Weimin, Kang, Sung-Hae L, Patel, Ankita, Krantz, Ian D, Raible, Sarah E, Smith, Wendy, Cristian, Ingrid, Torti, Erin, Juusola, Jane, Millan, Francisca, Wentzensen, Ingrid M, Person, Richard E, Küry, Sébastien, Bézieau, Stéphane, Uguen, Kévin, Férec, Claude, Munnich, Arnold, van Haelst, Mieke, Lichtenbelt, Klaske D, van Gassen, Koen, Hagelstrom, Tanner, Chawla, Aditi, Perry, Denise L, Taft, Ryan J, Jones, Marilyn, Masser-Frye, Diane, Dyment, David, Venkateswaran, Sunita, Li, Chumei, Escobar, Luis F, Horn, Denise, Spillmann, Rebecca C, Peña, Loren, Wierzba, Jolanta, Strom, Tim M, Parenti, Ilaria, Kaiser, Frank J, Ehmke, Nadja, and Schaaf, Christian P

Subjects
Biological Sciences, Genetics, Brain Disorders, Neurosciences, Behavioral and Social Science, Clinical Research, Pediatric, Congenital Structural Anomalies, Intellectual and Developmental Disabilities (IDD), Mental Health, Autism, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Autism Spectrum Disorder, Child, Child, Preschool, Chromosome Deletion, DNA-Binding Proteins, Genome, Human, Haploinsufficiency, Humans, Infant, Infant, Newborn, Intellectual Disability, Language Development Disorders, Neurodevelopmental Disorders, Nuclear Proteins, Phenotype, Problem Behavior, Proteins, Exome Sequencing, USP7, neurodevelopment, speech delay, white matter paucity, corpus callosum thinning, Clinical Sciences, Genetics & Heredity
Abstract

PurposeHaploinsufficiency of USP7, located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling.MethodsWe report 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on the seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency.ResultsThe clinical manifestations of these 23 individuals suggest a syndrome characterized by DD/ID, hypotonia, eye anomalies,feeding difficulties, GERD, behavioral anomalies, and ASD, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination.ConclusionThe consistency of clinical features among all individuals presented regardless of de novo USP7 variant type supports haploinsufficiency as a mechanism for pathogenesis and refines the clinical impact faced by affected individuals and caregivers.

Published
2019

3. USP7 Acts as a Molecular Rheostat to Promote WASH-Dependent Endosomal Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder

Author

Hao, Yi-Heng, Fountain, Michael D., Jr., Fon Tacer, Klementina, Xia, Fan, Bi, Weimin, Kang, Sung-Hae L., Patel, Ankita, Rosenfeld, Jill A., Le Caignec, Cédric, Isidor, Bertrand, Krantz, Ian D., Noon, Sarah E., Pfotenhauer, Jean P., Morgan, Thomas M., Moran, Rocio, Pedersen, Robert C., Saenz, Margarita S., Schaaf, Christian P., and Potts, Patrick Ryan

Published
2015
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4. Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

Author

McKnight, Dianalee, Morales, Ana, Hatchell, Kathryn E., Bristow, Sara L., Bonkowsky, Joshua L., Perry, Michael Scott, Berg, Anne T., Borlot, Felippe, Esplin, Edward D., Moretz, Chad, Angione, Katie, Ríos-Pohl, Loreto, Nussbaum, Robert L., Aradhya, Swaroop, Haldeman-Englert, Chad R., Levy, Rebecca J., Parachuri, Venu G., Lay-Son, Guillermo, De Montellano, David J. Dávila-Ortiz, Ramirez-Garcia, Miguel Angel, Benítez Alonso, Edmar O., Ziobro, Julie, Chirita-Emandi, Adela, Felix, Temis M., Kulasa-Luke, Dianne, Megarbane, Andre, Karkare, Shefali, Chagnon, Sarah L., Humberson, Jennifer B., Assaf, Melissa J., Silva, Sebastian, Zarroli, Katherine, Boyarchuk, Oksana, Nelson, Gary R., Palmquist, Rachel, Hammond, Katherine C., Hwang, Sean T., Boutlier, Susan B., Nolan, Melinda, Batley, Kaitlin Y., Chavda, Devraj, Reyes-Silva, Carlos Alberto, Miroshnikov, Oleksandr, Zuccarelli, Britton, Amlie-Wolf, Louise, Wheless, James W., Seinfeld, Syndi, Kanhangad, Manoj, Freeman, Jeremy L., Monroy-Santoyo, Susana, Rodriguez-Vazquez, Natalia, Ryan, Monique M., Machie, Michelle, Guerra, Patricio, Hassan, Muhammad Jawad, Candee, Meghan S., Bupp, Caleb P., Park, Kristen L., Muller, Eric, Lupo, Pamela, Pedersen, Robert C., Arain, Amir M., Murphy, Andrea, Schatz, Krista, Mu, Weiyi, Kalika, Paige M., Plaza, Lautaro, Kellogg, Marissa A., Lora, Evelyn G., Carson, Robert P., Svystilnyk, Victoria, Venegas, Viviana, Luke, Rebecca R., Jiang, Huiyuan, Stetsenko, Tetiana, Dueñas-Roque, Milagros M., Trasmonte, Joseph, Burke, Rebecca J., Hurst, Anna C. E., Smith, Douglas M., Massingham, Lauren J., Pisani, Laura, Costin, Carrie E., Ostrander, Betsy, Filloux, Francis M., Ananth, Amitha L., Mohamed, Ismail S., Nechai, Alla, Dao, Jasmin M., Fahey, Michael C., Aliu, Ermal, Falchek, Stephen, Press, Craig A., Treat, Lauren, Eschbach, Krista, Starks, Angela, Kammeyer, Ryan, Bear, Joshua J., Jacobson, Mona, Chernuha, Veronika, Meibos, Bailey, Wong, Kristen, Sweney, Matthew T., Espinoza, A. Chris, Van Orman, Colin B., Weinstock, Arie, Kumar, Ashutosh, Soler-Alfonso, Claudia, Nolan, Danielle A., Raza, Muhammad, Rojas Carrion, Miguel David, Chari, Geetha, Marsh, Eric D., Shiloh-Malawsky, Yael, Parikh, Sumit, Gonzalez-Giraldo, Ernesto, Fulton, Stephen, Sogawa, Yoshimi, Burns, Kaitlyn, Malets, Myroslava, Montiel Blanco, Johnny David, Habela, Christa W., Wilson, Carey A, Guzmán, Guillermo G., Pavliuk, Mariia, McKnight, Dianalee, Morales, Ana, Hatchell, Kathryn E., Bristow, Sara L., Bonkowsky, Joshua L., Perry, Michael Scott, Berg, Anne T., Borlot, Felippe, Esplin, Edward D., Moretz, Chad, Angione, Katie, Ríos-Pohl, Loreto, Nussbaum, Robert L., Aradhya, Swaroop, Haldeman-Englert, Chad R., Levy, Rebecca J., Parachuri, Venu G., Lay-Son, Guillermo, De Montellano, David J. Dávila-Ortiz, Ramirez-Garcia, Miguel Angel, Benítez Alonso, Edmar O., Ziobro, Julie, Chirita-Emandi, Adela, Felix, Temis M., Kulasa-Luke, Dianne, Megarbane, Andre, Karkare, Shefali, Chagnon, Sarah L., Humberson, Jennifer B., Assaf, Melissa J., Silva, Sebastian, Zarroli, Katherine, Boyarchuk, Oksana, Nelson, Gary R., Palmquist, Rachel, Hammond, Katherine C., Hwang, Sean T., Boutlier, Susan B., Nolan, Melinda, Batley, Kaitlin Y., Chavda, Devraj, Reyes-Silva, Carlos Alberto, Miroshnikov, Oleksandr, Zuccarelli, Britton, Amlie-Wolf, Louise, Wheless, James W., Seinfeld, Syndi, Kanhangad, Manoj, Freeman, Jeremy L., Monroy-Santoyo, Susana, Rodriguez-Vazquez, Natalia, Ryan, Monique M., Machie, Michelle, Guerra, Patricio, Hassan, Muhammad Jawad, Candee, Meghan S., Bupp, Caleb P., Park, Kristen L., Muller, Eric, Lupo, Pamela, Pedersen, Robert C., Arain, Amir M., Murphy, Andrea, Schatz, Krista, Mu, Weiyi, Kalika, Paige M., Plaza, Lautaro, Kellogg, Marissa A., Lora, Evelyn G., Carson, Robert P., Svystilnyk, Victoria, Venegas, Viviana, Luke, Rebecca R., Jiang, Huiyuan, Stetsenko, Tetiana, Dueñas-Roque, Milagros M., Trasmonte, Joseph, Burke, Rebecca J., Hurst, Anna C. E., Smith, Douglas M., Massingham, Lauren J., Pisani, Laura, Costin, Carrie E., Ostrander, Betsy, Filloux, Francis M., Ananth, Amitha L., Mohamed, Ismail S., Nechai, Alla, Dao, Jasmin M., Fahey, Michael C., Aliu, Ermal, Falchek, Stephen, Press, Craig A., Treat, Lauren, Eschbach, Krista, Starks, Angela, Kammeyer, Ryan, Bear, Joshua J., Jacobson, Mona, Chernuha, Veronika, Meibos, Bailey, Wong, Kristen, Sweney, Matthew T., Espinoza, A. Chris, Van Orman, Colin B., Weinstock, Arie, Kumar, Ashutosh, Soler-Alfonso, Claudia, Nolan, Danielle A., Raza, Muhammad, Rojas Carrion, Miguel David, Chari, Geetha, Marsh, Eric D., Shiloh-Malawsky, Yael, Parikh, Sumit, Gonzalez-Giraldo, Ernesto, Fulton, Stephen, Sogawa, Yoshimi, Burns, Kaitlyn, Malets, Myroslava, Montiel Blanco, Johnny David, Habela, Christa W., Wilson, Carey A, Guzmán, Guillermo G., and Pavliuk, Mariia

Abstract

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical informati

Published
2022

10. Sec. 901(m): potential trap for partnership transactions.

Author

Dokko, Sean, Roth, William F., III, and Pedersen, Robert C.

Subjects
Basis (Taxation) -- Laws, regulations and rules, Foreign source income taxation -- Laws, regulations and rules, Partnership -- Taxation, Government regulation, Internal Revenue Code (I.R.C. 901(m))
Abstract

In 2010, President Barack Obama signed P.L. 111-226, enacting new Sec. 901(m), which limits the creditability of foreign taxes in certain acquisition transactions where a taxpayer receives a basis step-up [...]

Published
2013

11. Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies

Author

Fountain, Michael D., Oleson, David S., Rech, Megan E., Segebrecht, Lara, Hunter, Jill V., McCarthy, John M., Lupo, Philip J., Holtgrewe, Manuel, Moran, Rocio, Rosenfeld, Jill A., Isidor, Bertrand, Le Caignec, Cédric, Saenz, Margarita S., Pedersen, Robert C., Morgan, Thomas M., Pfotenhauer, Jean P., Xia, Fan, Bi, Weimin, Kang, Sung Hae L., Patel, Ankita, Krantz, Ian D., Raible, Sarah E., Smith, Wendy, Cristian, Ingrid, Torti, Erin, Juusola, Jane, Millan, Francisca, Wentzensen, Ingrid M., Person, Richard E., Küry, Sébastien, Bézieau, Stéphane, Uguen, Kévin, Férec, Claude, Munnich, Arnold, van Haelst, Mieke, Lichtenbelt, Klaske D., van Gassen, Koen, Hagelstrom, Tanner, Chawla, Aditi, Perry, Denise L., Taft, Ryan J., Jones, Marilyn, Masser-Frye, Diane, Dyment, David, Venkateswaran, Sunita, Li, Chumei, Escobar, Luis F., Horn, Denise, Spillmann, Rebecca C., Peña, Loren, Wierzba, Jolanta, Strom, Tim M., Parenti, Ilaria, Kaiser, Frank J., Ehmke, Nadja, Schaaf, Christian P., Fountain, Michael D., Oleson, David S., Rech, Megan E., Segebrecht, Lara, Hunter, Jill V., McCarthy, John M., Lupo, Philip J., Holtgrewe, Manuel, Moran, Rocio, Rosenfeld, Jill A., Isidor, Bertrand, Le Caignec, Cédric, Saenz, Margarita S., Pedersen, Robert C., Morgan, Thomas M., Pfotenhauer, Jean P., Xia, Fan, Bi, Weimin, Kang, Sung Hae L., Patel, Ankita, Krantz, Ian D., Raible, Sarah E., Smith, Wendy, Cristian, Ingrid, Torti, Erin, Juusola, Jane, Millan, Francisca, Wentzensen, Ingrid M., Person, Richard E., Küry, Sébastien, Bézieau, Stéphane, Uguen, Kévin, Férec, Claude, Munnich, Arnold, van Haelst, Mieke, Lichtenbelt, Klaske D., van Gassen, Koen, Hagelstrom, Tanner, Chawla, Aditi, Perry, Denise L., Taft, Ryan J., Jones, Marilyn, Masser-Frye, Diane, Dyment, David, Venkateswaran, Sunita, Li, Chumei, Escobar, Luis F., Horn, Denise, Spillmann, Rebecca C., Peña, Loren, Wierzba, Jolanta, Strom, Tim M., Parenti, Ilaria, Kaiser, Frank J., Ehmke, Nadja, and Schaaf, Christian P.

Published
2019

12. Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies

Author

Genetica, UMC Utrecht, Genetica Klinische Genetica, Child Health, Genetica Sectie Genoomdiagnostiek, Fountain, Michael D., Oleson, David S., Rech, Megan E., Segebrecht, Lara, Hunter, Jill V., McCarthy, John M., Lupo, Philip J., Holtgrewe, Manuel, Moran, Rocio, Rosenfeld, Jill A., Isidor, Bertrand, Le Caignec, Cédric, Saenz, Margarita S., Pedersen, Robert C., Morgan, Thomas M., Pfotenhauer, Jean P., Xia, Fan, Bi, Weimin, Kang, Sung Hae L., Patel, Ankita, Krantz, Ian D., Raible, Sarah E., Smith, Wendy, Cristian, Ingrid, Torti, Erin, Juusola, Jane, Millan, Francisca, Wentzensen, Ingrid M., Person, Richard E., Küry, Sébastien, Bézieau, Stéphane, Uguen, Kévin, Férec, Claude, Munnich, Arnold, van Haelst, Mieke, Lichtenbelt, Klaske D., van Gassen, Koen, Hagelstrom, Tanner, Chawla, Aditi, Perry, Denise L., Taft, Ryan J., Jones, Marilyn, Masser-Frye, Diane, Dyment, David, Venkateswaran, Sunita, Li, Chumei, Escobar, Luis F., Horn, Denise, Spillmann, Rebecca C., Peña, Loren, Wierzba, Jolanta, Strom, Tim M., Parenti, Ilaria, Kaiser, Frank J., Ehmke, Nadja, Schaaf, Christian P., Genetica, UMC Utrecht, Genetica Klinische Genetica, Child Health, Genetica Sectie Genoomdiagnostiek, Fountain, Michael D., Oleson, David S., Rech, Megan E., Segebrecht, Lara, Hunter, Jill V., McCarthy, John M., Lupo, Philip J., Holtgrewe, Manuel, Moran, Rocio, Rosenfeld, Jill A., Isidor, Bertrand, Le Caignec, Cédric, Saenz, Margarita S., Pedersen, Robert C., Morgan, Thomas M., Pfotenhauer, Jean P., Xia, Fan, Bi, Weimin, Kang, Sung Hae L., Patel, Ankita, Krantz, Ian D., Raible, Sarah E., Smith, Wendy, Cristian, Ingrid, Torti, Erin, Juusola, Jane, Millan, Francisca, Wentzensen, Ingrid M., Person, Richard E., Küry, Sébastien, Bézieau, Stéphane, Uguen, Kévin, Férec, Claude, Munnich, Arnold, van Haelst, Mieke, Lichtenbelt, Klaske D., van Gassen, Koen, Hagelstrom, Tanner, Chawla, Aditi, Perry, Denise L., Taft, Ryan J., Jones, Marilyn, Masser-Frye, Diane, Dyment, David, Venkateswaran, Sunita, Li, Chumei, Escobar, Luis F., Horn, Denise, Spillmann, Rebecca C., Peña, Loren, Wierzba, Jolanta, Strom, Tim M., Parenti, Ilaria, Kaiser, Frank J., Ehmke, Nadja, and Schaaf, Christian P.

Published
2019

13. When does e-commerce create a PE?

Author

Levin, Leonard D. and Pedersen, Robert C.

Subjects
Organisation for Economic Co-operation and Development -- Models -- Taxation, Electronic commerce -- Taxation -- Analysis -- Models, Tax law -- Analysis -- Models, Domicile in taxation -- Analysis -- Models, Electronic commerce, Tax law
Abstract

The growth of electronic commerce faces an increasing risk of double taxation, unless steps are taken to develop a uniform approach as to whether an enterprise's Website is a taxable [...]

Published
2000

18. Sec. 704(c)'s anti-abuse rule: a practitioner's guide.

Author

Drew, Walter R. and Pedersen, Robert C.

Subjects
Tax planning -- Laws, regulations and rules, Partnership -- Taxation -- Laws, regulations and rules, Government regulation, Internal Revenue Code (I.R.C. 704(c))
Abstract

Sec. 704(c)'s purpose is to prevent shifting of tax consequences among partners that can occur when property is contributed to a partnership with a fair market value that differs from [...]

Published
1997

27. Reviewing Internet mailing lists.

Author

Pedersen, Robert C.

Subjects
*INTERNET forums, *INTERNET
Abstract

Discusses the potential benefits of Internet mailing lists to subscribers. What are the aspects of mailing lists; Description of benefits; Methods used in reviewing Internet mailing lists.

Published
1996

30. What Syndrome Is This?

Author

Mallory, Susan B., Krafchik, Bernice R., Allison, Matthew A., Dunn, Cary L., and Pedersen, Robert C.

Subjects
NEUROLOGICAL disorders, CHILDREN, HEALTH
Abstract

Presents the case of a Caucasian girl with epidermal nevus syndrome (ENS). Reference to neurologic abnormalities; Basis of the classification of ENS; Characteristics of the disease.

Published
1998

44. Reviews.

Author

Pedersen, Robert C. and Cole, Jim E.

Subjects
WHOLE Internet User's Guide & Catalog, The (Book)
Abstract

Reviews the book `The Whole Internet User's Guide & Catalog,' by Ed Krol.

Published
1993

48. Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Author

McKnight D, Morales A, Hatchell KE, Bristow SL, Bonkowsky JL, Perry MS, Berg AT, Borlot F, Esplin ED, Moretz C, Angione K, Ríos-Pohl L, Nussbaum RL, Aradhya S, Haldeman-Englert CR, Levy RJ, Parachuri VG, Lay-Son G, de Montellano DJD, Ramirez-Garcia MA, Benítez Alonso EO, Ziobro J, Chirita-Emandi A, Felix TM, Kulasa-Luke D, Megarbane A, Karkare S, Chagnon SL, Humberson JB, Assaf MJ, Silva S, Zarroli K, Boyarchuk O, Nelson GR, Palmquist R, Hammond KC, Hwang ST, Boutlier SB, Nolan M, Batley KY, Chavda D, Reyes-Silva CA, Miroshnikov O, Zuccarelli B, Amlie-Wolf L, Wheless JW, Seinfeld S, Kanhangad M, Freeman JL, Monroy-Santoyo S, Rodriguez-Vazquez N, Ryan MM, Machie M, Guerra P, Hassan MJ, Candee MS, Bupp CP, Park KL, Muller E 2nd, Lupo P, Pedersen RC, Arain AM, Murphy A, Schatz K, Mu W, Kalika PM, Plaza L, Kellogg MA, Lora EG, Carson RP, Svystilnyk V, Venegas V, Luke RR, Jiang H, Stetsenko T, Dueñas-Roque MM, Trasmonte J, Burke RJ, Hurst ACE, Smith DM, Massingham LJ, Pisani L, Costin CE, Ostrander B, Filloux FM, Ananth AL, Mohamed IS, Nechai A, Dao JM, Fahey MC, Aliu E, Falchek S, Press CA, Treat L, Eschbach K, Starks A, Kammeyer R, Bear JJ, Jacobson M, Chernuha V, Meibos B, Wong K, Sweney MT, Espinoza AC, Van Orman CB, Weinstock A, Kumar A, Soler-Alfonso C, Nolan DA, Raza M, Rojas Carrion MD, Chari G, Marsh ED, Shiloh-Malawsky Y, Parikh S, Gonzalez-Giraldo E, Fulton S, Sogawa Y, Burns K, Malets M, Montiel Blanco JD, Habela CW, Wilson CA, Guzmán GG, and Pavliuk M

Subjects
Humans, Female, Infant, Newborn, Infant, Child, Preschool, Child, Adolescent, Young Adult, Adult, Middle Aged, Male, Retrospective Studies, Cross-Sectional Studies, Seizures genetics, Genetic Testing methods, Epilepsy drug therapy, Epilepsy genetics
Abstract

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes., Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes., Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals., Exposures: Genetic test results., Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms., Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%)., Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Published
2022
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