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Master of Public Health

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

AUTHORS

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 , 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 , Pavliuk M , . JAMA neurology. 2022 10 31; ().

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.

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