2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-<em>QRICH1</em>-related disorder: Phenotype expansion versus blended phenotype

Pdf Summary

QRICH1-related disorder is a rare developmental disorder characterized by variable intellectual disability, developmental delay, hypotonia, short stature, seizure, scoliosis, poor weight gain, and subtle facial dysmorphism. This case study presents a patient with a unique clinical phenotype, including a pathogenic variant in the QRICH1 gene. The patient also presented with a tumor (nephroblastoma) and aortic root aneurysm, which have not been reported in other cases of QRICH1-related disorder.<br /><br />The researchers suggest that the diverse and complex array of manifestations in this patient cannot be explained by a single molecular etiology. They propose that both established disease genes (QRICH1, LZTR1) and novel disease gene candidates may contribute to the patient's blended phenotype, which includes multiple tumors (hepatoblastoma, gingival fibromas, and follicular adenoma) and aortic root aneurysm, in addition to intellectual disability.<br /><br />The LZTR1 gene, associated with AD/AR Noonan syndrome and susceptibility to Schwannomas, is suggested to play a critical role in the Ras pathway and potentially contribute to the patient's tumor susceptibility and phenotype. The case emphasizes the importance of re-evaluating patients for new findings and highlights that apparent phenotypic expansion may actually represent blended phenotypes resulting from variation at more than one locus.<br /><br />Overall, this case study highlights the complexity of QRICH1-related disorder and the need for further research to better understand its molecular underpinnings and the genetic factors contributing to the variable phenotype.

Asset Subtitle

Presenting Author - Gulsen Akay, MD; Co-Author - Vanina Taliercio, MD; Co-Author - Janice Palumbos, MS, CGC; Co-Author - David H. Viskochil, MD, PhD;

Meta Tag

Cognitive Disorders

Dysmorphology

Exome sequencing

Genetic Testing

Intellectual disability

Sequencing

Co-Author Vanina Taliercio, MD

Co-Author Janice Palumbos, MS, CGC

Co-Author David H. Viskochil, MD, PhD

Presenting Author Gulsen Akay, MD

Keywords

QRICH1-related disorder

developmental delay

intellectual disability

seizure

scoliosis

tumor

nephroblastoma

aortic root aneurysm

LZTR1

genetic factors