Predictors of whole exome sequencing in dystonic cerebral palsy and cerebral palsy-like disorders

• Published in: Parkinsonism & related disorders Vol. 111; p. 105352
• Main Authors: Pavelekova, P., Necpal, J., Jech, R., Havrankova, P., Svantnerova, J., Jurkova, V., Gdovinova, Z., Lackova, A., Han, V., Winkelmann, J., Zech, M., Skorvanek, M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2023
• Subjects: Brain; Cerebral palsy; Cerebral Palsy - genetics; Cerebral palsy-like; Dystonia - complications; Dystonia - genetics; Dystonic cerebral palsy; Dystonic Disorders - complications; Dystonic Disorders - genetics; Exome Sequencing; Humans; Male; WES; Whole exome sequencing; Cerebral palsy; Cerebral palsy-like; Dystonic cerebral palsy; WES; Whole exome sequencing
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2023.105352

Cerebral palsy (CP) is a group of permanent disorders attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. Cerebral palsy-like (CP-like) disorders may clinically resemble CP but do not fulfill CP criteria and have often a progressive course and/or neurodevelopmental regression. To assess which patients with dystonic CP and dystonic CP-like disorder should undergo Whole Exome Sequencing (WES), we compared the rate of likely causative variants in individuals regarding their clinical picture, co-morbidities, and environmental risk factors. Individuals with early onset neurodevelopmental disorder (ND) manifesting with dystonia as a core feature were divided into CP or CP-like cohorts based on their clinical picture and disease course. Detailed clinical picture, co-morbidities, and environmental risk factors including prematurity, asphyxia, SIRS, IRDS, and cerebral bleeding were evaluated. A total of 122 patients were included and divided into the CP group with 70 subjects (30 males; mean age 18y5m±16y6m, mean GMFCS score 3.3 ± 1.4), and the CP-like group with 52 subjects (29 males; mean age 17y7m±1y,6 m, mean GMFCS score 2,6 ± 1,5). The WES-based diagnosis was present in 19 (27.1%) CP patients and 30 CP-like patients (57.7%) with genetic conditions overlap in both groups. We found significant differences in diagnostic rate in CP individuals with vs. without risk factors (13.9% vs. 43.3%); Fisher's exact p = 0.0065. We did not observe the same tendency in CP-like (45.5% vs 58.5%); Fisher's exact p = 0.5. WES is a useful diagnostic method for patients with dystonic ND, regardless of their presentation as a CP or CP-like phenotype. •There is a huge overlap in genetic diagnosis between patient with dystonic cerebral palsy and cerebral palsy-like disorders.•Predictive score for WES-based diagnosis in dystonic CP and CP-like cases.•There is a significant difference in WES diagnostic rate in dystonic cerebral patients in patients with vs. without risk factors.•There is no significant difference in WES diagnostic rate in dystonic CP-like with vs. without risk factors.