2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-<em>SATB2</em>-Associated Syndrome Severity Score: Genotype/phenotype Correlations and the SATB2 Portal

Pdf Summary

The SATB2-Associated syndrome (SAS) severity score is a tool for assessing the severity of the genetic disorder. SAS is characterized by developmental delays, behavioral abnormalities, facial dysmorphism, dental problems, and skeletal anomalies. The lack of a standardized tool to measure disease severity has made it difficult to establish genotype-phenotype correlations. The severity scoring system proposed in this study provides a quantitative and standardized assessment of clinical severity in SAS.<br /><br />The severity score is based on a rubric that includes 15 different individual features grouped into neurodevelopmental and systemic categories. These features measure common phenotypic traits in SAS, such as cognitive abilities, language development, behavior, sleep patterns, and physical characteristics.<br /><br />The study enrolled 164 individuals with a confirmed diagnosis of SAS. The severity scores were higher for certain genetic variants, such as null variants located after amino acid 350, the common missense variant Arg389Cys, intragenic deletions, and larger chromosomal deletions. Deletion sizes were also correlated with higher neurodevelopmental and total scores.<br /><br />Individuals with chromosomal abnormalities had higher scores for palate, feeding and growth, while missense variant carriers had higher scores for scoliosis. The missense variant Arg389Cys was associated with the most severe cognitive, verbal, and sialorrhea (drooling) scores. Chromosomal deletions larger than 6Mb were associated with higher scores in multiple categories.<br /><br />The SATB2 Portal, an online resource, provides access to the severity scoring rubric for healthcare providers and families. The scoring system is still being refined and validated, and further research is needed to fully integrate genotype and phenotype information. The severity score has the potential to be used in clinical counseling and future clinical trials of SAS.

Asset Subtitle

Presenting Author - Yuri Zarate, MD, MBA, FACMG; Co-Author - Katherine Bosanko, MS, LCGC; Co-Author - Amrit Kannan, MS; Co-Author - Ashlen Thomason, PhD; Co-Author - Beth Nutt, MS; Co-Author - Nihit Kumar, MD; Co-Author - Kirk Simmons, MD; Co-Author - Aaron Hiegert, DMD; Co-Author - Larry Hartzell, MD; Co-Author - Adam Johnson, MD; Co-Author - Tabitha Prater, RD; Co-Author - Jillian Kimberlain, AUD; Co-Author - Aisling Caffrey, PhD; Co-Author - Arthur Stefanski, MS; Co-Author - Tobias Brünger, MS; Co-Author - Eduardo Pérez-Palma, PhD; Co-Author - Dennis Lal, MD;

Meta Tag

Clinical History

Delineation of Diseases

Genetic Testing

Genotype-Phenotype Correlations

Phenotype

Phenotypic delineation of disorders

Visual System

Co-Author Katherine Bosanko, MS, LCGC

Co-Author Amrit Kannan, MS

Co-Author Ashlen Thomason, PhD

Co-Author Beth Nutt, MS

Co-Author Nihit Kumar, MD

Co-Author Kirk Simmons, MD

Co-Author Aaron Hiegert, DMD

Co-Author Larry Hartzell, MD

Co-Author Adam Johnson, MD

Co-Author Tabitha Prater, RD

Co-Author Jillian Kimberlain, AUD

Co-Author Aisling Caffrey, PhD

Co-Author Arthur Stefanski, MS

Co-Author Tobias Brünger, MS

Co-Author Eduardo Pérez-Palma, PhD

Co-Author Dennis Lal, MD

Presenting Author Yuri Zarate, MD, MBA, FACMG

Keywords

SATB2-Associated syndrome

SAS

severity score

genetic disorder

developmental delays

behavioral abnormalities

facial dysmorphism

dental problems

skeletal anomalies

genotype-phenotype correlations