![]() History may be obtained from the affected individual and witnesses, supplemented if necessary by video EEG monitoring. More detailed information for clinicians ordering genetic tests can be found here. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.įor an introduction to multigene panels click here. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. Notes: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. When the phenotypic and EEG findings suggest the diagnosis of ADSHE, molecular genetic testing approaches can include use of a multigene panel.Īn epilepsy multigene panel that includes CABP4, CHRNA2, CHRNA4, CHRNB2, CRH, DEPDC5, KCNT1, NPRL2, NPR元, and STX1B (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Individuals with the clinical findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other epilepsy phenotypes are more likely to be diagnosed using genomic testing (see Option 2). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. ![]() Molecular genetic testing approaches can include a combination of gene-targeted testing ( multigene panel) and comprehensive genomic testing ( exome sequencing, genome sequencing) depending on the phenotype. (2) Identification of a heterozygous variant of uncertain significance in any of the genes in Table 1 does not establish or rule out the diagnosis. ![]() Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms " pathogenic variant" and " likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making. A pathogenic variant is identified in 19% of individuals with a family history of SHE and 7% of individuals with a negative family history. A molecular diagnosis of ADSHE is established in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in in one of the genes listed in Table 1. Transitioning to a lower-risk medication prior to pregnancy may be possible.Ī clinical diagnosis of ADSHE is established in a proband based on the presence of clinical features, EEG findings and family history detailed in Suggestive Findings. Pregnancy management: Discussion of the risks and benefits of using a given ASM during pregnancy should ideally take place prior to conception. Surveillance: Reevaluation of EEGs at regular intervals to monitor disease progression, as well as assessment for changes in seizure semiology, changes in tone, and movement disorders monitoring of developmental progress and educational needs.Įvaluation of relatives at risk: A medical history from relatives at risk can identify those with ADSHE so that treatment can be initiated promptly. Adjunctive fenofibrate therapy or vagal nerve stimulation may be considered in individuals resistant to standard ASM. Resistance to ASM is present in about 30% of affected individuals and typically requires a trial of all appropriate ASM. KCNT1-related ADSHE is difficult to treat but may be treatable using quinidine based on limited data. Individuals with ADSHE associated with the CHRNA4 pathogenic variant p.Ser284Leu are more responsive to zonisamide than carbamazepine. ![]() Carbamazepine is associated with remission in about 70% of individuals, often in relatively low doses. Treatment of manifestations: Many anti-seizure medications (ASM) may be effective.
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