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

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.

Varones 46, XX: a propósito de dos casos genéticamente distintos / Males 46, XX: Presentation of Two Genetically Different Cases

Introducción Los desórdenes de diferenciación sexual son condiciones clínicas en las que existe una discrepancia entre el sexo cromosómico y el sexo fenotípico de un individuo. Esas condiciones suelen resultar angustiantes para los pacientes y sus familias e incluso para el equipo médico tratante debido a la dificultad en diagnosticarlas. Objetivo Presentar las características clínicas, genéticas y hormonales de dos varones con desórdenes de diferenciación sexual. Método Se realizó un estudio descriptivo basado en la revisión y análisis de datos de la historia clínica y la confrontación de los resultados con reportes similares. Resultados Se observaron dos individuos con fenotipo masculino y diagnóstico de hipogonadismo hipergonadotrófico con cariotipo 46, XX. El primer caso presentó testes pequeños y azoospermia, mientras que el segundo caso presentó baja talla, criptorquidea bilateral congénita y escrotos hipoplásicos. En ambos pacientes se exploró la presencia del gen SRY, confirmando su presencia en el primer caso y ausencia en el segundo caso. Conclusiones El diagnóstico genético-molecular actual apela a la combinación de técnicas tradicionales junto a técnicas modernas, como secuenciación por paneles genéticos a fin de identificar etiológicamente los desórdenes de diferenciación sexual. La presentación de esos casos aún se considera rara debido a su baja tasa de frecuencia poblacional, por lo que su reporte siempre resultará útil a la comunidad científica ya que muestran las distintas formas de presentación clínica y el manejo multidisciplinario de esos casos en diferentes contextos clínicos

Introduction Disorders of Sexual Development are clinical conditions in which a discrepancy between the chromosomal sex and the phenotypic sex occurs in an individual. These conditions are often distressing for patients and their families and even for the medical team due to the difficulty of diagnosing them. Objective The aim of this study was to present the clinical, genetic and hormonal characteristics of two males with sexual differentiation disorders. Method A descriptive study was performed based on the review and analysis of the clinical history data and the comparison of the results with similar cases reported. Results Two individuals with a male phenotype and a diagnosis of hypogonadotropic hypogonadism with 46, XX karyotype were observed. The first case presented small testes and azoospermia, while the second case presented low height, congenital bilateral cryptorchid and hypoplastic scrotums. The SRY gene was explored in both patients, and it was confirmed its presence in the first case and its absence in the second case. Conclusions The current molecular-genetic diagnosis calls for the combination of traditional techniques combined with modern techniques, such as the genetic panel sequencing, to identify etiologically the Disorders of Sexual Development. The presentation of these cases is even considered rare because of their low population frequency rate, so their report is always useful to the scientific community, for they show the different ways of the clinical disease presentation and the multidisciplinary management of these cases in different clinical contexts.