2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-2q11.2 Recurrent CNVs Including TMEM127 - A Collaborative Multi-Center Study to Expand Knowledge of Neurodevelopmental Phenotypes and Pheochromocytoma/Paraganglioma Syndrome Predisposition

2q11.2 Recurrent CNVs Including TMEM127 - A Collaborative Multi-Center Study to Expand Knowledge of Neurodevelopmental Phenotypes and Pheochromocytoma/Paraganglioma Syndrome Predisposition

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The study aims to expand knowledge on the clinical phenotypes associated with recurrent copy number variants (CNVs) on the 2q11.2 region, specifically the neurodevelopmental phenotypes and the predisposition to pheochromocytoma/paraganglioma syndrome (PCC/PGL) due to the TMEM127 gene within this region. The study involves a collaborative multi-center approach to gather data on patients with 2q11.2 CNVs.<br /><br />The results of the study show that individuals with 2q11.2 deletions exhibit neurodevelopmental phenotypes such as autism, intellectual disability, seizures, depression, anxiety, sleep disturbance, and trouble concentrating. On the other hand, individuals with 2q11.2 duplications may experience high blood pressure, fatigue, arrhythmias, palpitations, dysphagia, headaches, nausea, impaired glycemic control, high blood pulse, paleness, weight loss, excessive sweating, voice changes, and tinnitus.<br /><br />The study did not identify any individuals with a known diagnosis of PCC/PGL, possibly due to a later age of onset or variable age-related penetrance. However, phenotypes associated with PCC/PGL were frequent among individuals with 2q11.2 deletions. Ongoing analysis is being conducted to determine the true risk of developing PCC/PGL in individuals with the 2q11.2 deletion.<br /><br />Based on the inclusion of the TMEM127 gene in the ACMG SF v3.0 list, the 2q11.2 deletion is now considered pathogenic. The study recommends disclosing the new information regarding possible PCC/PGL risk among individuals with the 2q11.2 deletion. The findings of the study aim to improve prognosis and clinical management for individuals with 2q11.2 CNVs and their carrier family members.<br /><br />This study provides valuable insights into the phenotypic associations with 2q11.2 CNVs, particularly in terms of neurodevelopmental and PCC/PGL-related phenotypes. Further research and analysis are needed to fully understand the risks and implications associated with these genetic variants.

Asset Subtitle

Presenting Author - Lucilla Pizzo, PhD; Co-Author - Zoe K. Lewis, MS, CGC; Co-Author - Lauren K. Walsh, MS; Co-Author - Cassandra K. Runke, MS; Co-Author - Margit Nõukas, PhD; Co-Author - Katrin Männik, PhD; Co-Author - Neeme Tõnisson, MD, PhD; Co-Author - Eric C. Thorland, PhD; Co-Author - Christa L. Martin; Co-Author - Katherine M. Rudd, PhD; Co-Author - Erica F. Andersen, PhD, FACMG;

Meta Tag

array CGH

Brain/Nervous System

Cancer Syndromes

Cognitive Disorders

Intellectual disability

Microarray

Pathogenesis

Phenotypic delineation of disorders

Co-Author Zoe K. Lewis, MS, CGC

Co-Author Lauren K. Walsh, MS

Co-Author Cassandra K. Runke, MS

Co-Author Margit Nõukas, PhD

Co-Author Katrin Männik, PhD

Co-Author Neeme Tõnisson, MD, PhD

Co-Author Eric C. Thorland, PhD

Co-Author Christa L. Martin

Co-Author Katherine M. Rudd, PhD

Co-Author Erica F. Andersen, PhD, FACMG

Presenting Author Lucilla Pizzo, PhD

Keywords

clinical phenotypes

CNVs

2q11.2 region

neurodevelopmental phenotypes

PCC/PGL

TMEM127 gene

collaborative approach

high blood pressure

genetic variants

prognosis