2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Genetic Testing Strategies for Rare and Undiagnosed Neurogenetic Conditions: Utilization of Exome Sequencing, Metabolic, and Panel testing

Pdf Summary

This document is a poster template discussing genetic testing strategies for rare and undiagnosed neurogenetic conditions. The poster presents three case summaries to illustrate the challenges of current diagnostic strategies and propose strategies to improve diagnostic yield.<br /><br />Case 1: The patient had nonketotic hyperglycinemia (NKH) with symptoms including muscle weakness, hypotonia, respiratory distress, and feeding difficulty. Various tests were performed, including metabolic testing, nerve conduction studies, muscle biopsy, and genetic testing. Nondiagnostic results were obtained until a neuromuscular panel revealed two pathogenic variants in the NEB gene.<br /><br />Case 2: The patient had a copy number variant in 4p16.3, potentially indicating 4p microduplication syndrome. However, the variant is currently classified as a variant of unknown significance (VUS). The poster highlights the importance of using exome sequencing (ES) and chromosomal microarray (CMA) as comprehensive diagnostic tests and mentions the benefits of exome reanalysis and deep phenotyping.<br /><br />Case 3: The patient had sleep apnea, bradycardia, increased muscle tone, and other clinical features. Initial testing, including EEG and MRI, did not yield a diagnosis. However, reanalysis of the patient's exome sequencing seven years later revealed a possible pathogenic variant in 4p16.3. The poster emphasizes the advantages of updated clinical information and the potential for improved diagnostic yield with reanalysis.<br /><br />The conclusion of the poster highlights the heterogeneity of neurogenetic conditions, the challenges in diagnosing rare disorders, and the need for improved data analysis and variant interpretation. It suggests strategies such as exome reanalysis coupled with metabolomics and deep phenotyping, as well as panel testing after exome sequencing. The poster also discusses the importance of updating exome testing to capture new gene discoveries and advancements in bioinformatics. Finally, it briefly mentions specific conditions like nonketotic hyperglycinemia and Nemaline myopathy.

Asset Subtitle

Presenting Author - Roa Sadat, MMSc; Co-Author - Daniel Calame, MD PhD; Co-Author - Lisa T. Emrick, MD;

Meta Tag

Variant Detection

Phenotype

NextGen Sequencing

Neuroscience

Musculoskeletal system

Metabolic Disorder

Genomic Methodologies

Genetic Testing

Exome sequencing

Clinical History

Chromosomal Abnormalities

Brain/Nervous System

Biochemical genetics

Co-Author Lisa T. Emrick, MD

Co-Author Daniel Calame, MD PhD

Presenting Author Roa Sadat, MMSc

Keywords

genetic testing strategies

rare neurogenetic conditions

undiagnosed neurogenetic conditions

diagnostic strategies

nonketotic hyperglycinemia

exome sequencing

chromosomal microarray

exome reanalysis

deep phenotyping

4p microduplication syndrome