Utility of Exome Sequencing for Diagnosis in Unexplained Pediatric-Onset Epilepsy.

Importance: Genomic advances inform our understanding of epilepsy and can be translated to patients as precision diagnoses that influence clinical treatment, prognosis, and counseling.

Objective: To delineate the genetic landscape of pediatric epilepsy and clinical utility of genetic diagnoses for patients with epilepsy.

Design, Setting, And Participants: This cohort study used phenotypic data from medical records and treating clinicians at a pediatric hospital to identify patients with unexplained pediatric-onset epilepsy.

Mutations in and in a patient with early-onset epileptic encephalopathy and respiratory depression.

Early infantile epileptic encephalopathy (EIEE) is a severe disorder associated with epilepsy, developmental delay and intellectual disability, and in some cases premature mortality. We report the case of a female infant with EIEE and strikingly suppressed respiratory dysfunction that led to death. Postmortem research evaluation revealed hypoplasia of the arcuate nucleus of the medulla, a candidate region for respiratory regulation.

Variability Among Next-Generation Sequencing Panels for Early-Life Epilepsies.

This study compares the potential diagnostic yield of commercially available epilepsy panels to detect the genetic findings identified in a recently published cohort of early-life epilepsy.

PCDH19-related epilepsy is associated with a broad neurodevelopmental spectrum.

Objective: To characterize the features associated with PCDH19-related epilepsy, also known as "female-limited epilepsy."

Methods: We analyzed data from participants enrolled in the PCDH19 Registry, focusing on the seizure-related, developmental, neurobehavioral, and sleep-related features. We evaluated variants for pathogenicity based on previous reports, population databases, and in silico predictions, and included individuals with pathogenic or potentially pathogenic variants.

Compound heterozygosity with : Pushing the phenotypic envelope in genetic epilepsies.

pathogenic variants have been described in benign familial infantile epilepsy, episodic ataxia, paroxysmal kinesigenic dyskinesia, and hemiplegic migraines. We describe a patient with compound heterozygous variants, infantile epilepsy with status epilepticus, paroxysmal dyskinesia and episodic ataxia. Testing revealed a pathogenic duplication (c.

Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression.

Objective: We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and early myoclonic encephalopathy) and evaluate genotype-phenotype correlations.

Methods: We enrolled 33 patients with a referral diagnosis of Ohtahara syndrome or early myoclonic encephalopathy without malformations of cortical development. We performed detailed phenotypic assessment including seizure presentation, electroencephalography, and magnetic resonance imaging.

A Model Program for Translational Medicine in Epilepsy Genetics.

Recent technological advances in gene sequencing have led to a rapid increase in gene discovery in epilepsy. However, the ability to assess pathogenicity of variants, provide functional analysis, and develop targeted therapies has not kept pace with rapid advances in sequencing technology. Thus, although clinical genetic testing may lead to a specific molecular diagnosis for some patients, test results often lead to more questions than answers.

Parental interest in a genetic risk assessment test for autism spectrum disorders.

To better understand parental opinions regarding the diagnostic process and use of genetic testing to assess risk for autism spectrum disorders (ASDs) in the younger siblings of affected children in the Unites States, we conducted a survey of parents who had at least one child with ASD. A total of 162 surveys were completed anonymously using an Internet-based survey tool. The mean reported time to ASD diagnosis and age at diagnosis were 35.

Clinical genetic testing for patients with autism spectrum disorders.

Background: Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established.

Patients And Methods: A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008.

Psychiatric disorders in clinical genetics II: Individualizing recurrence risks.

This is the second article of a two-part professional development series on genetic counseling for personal and family histories of psychiatric disorders. It is based on an Educational Breakout Session presented by The Psychiatric Special Interest Group of the National Society of Genetic Counselors at the 2006 Annual Education Conference. While the first article in this two part series dealt with addressing family histories of psychiatric disorders in clinical practice, the following discussion deals with the generation and provision of individualized recurrence risks for psychiatric disorders, based on empiric risk data.

Psychiatric disorders in clinical genetics I: Addressing family histories of psychiatric illness.

This is the first article of a two-part professional development series addressing genetic counseling for personal and family histories of psychiatric disorders. It is based on an Educational Breakout Session presented by the Psychiatric Special Interest Group of the National Society of Genetic Counselors at the 2006 Annual Education Conference. This article examines issues that arise in addressing family histories of psychiatric illness, while the second article in the series considers the generation and provision of individualized recurrence risks for psychiatric disorders.

Communicative competence in parents of children with autism and parents of children with specific language impairment.

While the primary language deficit in autism has been thought to be pragmatic, and in specific language impairment (SLI) structural, recent research suggests phenomenological and possibly genetic overlap between the two syndromes. To compare communicative competence in parents of children with autism, SLI, and down syndrome (DS), we used a modified pragmatic rating scale (PRS-M). Videotapes of conversational interviews with 47 autism, 47 SLI, and 21 DS parents were scored blind to group membership.

Autism-related language, personality, and cognition in people with absolute pitch: results of a preliminary study.

Reports of a relatively high prevalence of absolute pitch (AP) in autistic disorder suggest that AP is associated with some of the distinctive cognitive and social characteristics seen in autism spectrum disorders. Accordingly we examined cognition, personality, social behavior, and language in 13 musicians with strictly defined AP (APS) and 33 musician controls (MC) without AP using standardized interviews and tests previously applied to identify the broad autism phenotype seen in the relatives of autistic probands. These included the Pragmatic Rating Scale (PRS) (social aspects of language) the Personality Assessment Schedule (PAS) (rigidity, aloofness, anxiety/worry, hypersensitivity), and WAIS performance subtests (PIQ).