2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Kidney Features in Patients with a Molecular Diagnosis of Birt-Hogg-Dubé Syndrome: A Case Series

Pdf Summary

This study examined the kidney disease phenotype of Birt-Hogg-Dubé syndrome (BHDS) in individuals with pathogenic or likely pathogenic variants in the folliculin gene (FLCN). The study included 25 cases, with the majority being female and the average age being 56.8 years. Seventeen unique FLCN variants were reported, with most of them being loss-of-function variants. Of the 25 FLCN positive cases, 20% had multiple positive genetic findings, including one triple positive case and four dual positive cases.<br /><br />The kidney disease phenotypes observed in the study cohort included chronic kidney disease (CKD), kidney cysts, and proteinuria. Some patients had a combination of these kidney features. Notably, none of the cases had a history of renal cancer. The prevalence of renal cell carcinoma (RCC) in BHDS may be overestimated, and noncancerous kidney features, such as polycystic kidneys, can be present in BHDS.<br /><br />The study highlights that broad panel kidney disease genetic testing can identify BHDS in patients without classic features and who would not meet the clinical diagnostic criteria. Only a small number of cases had a known diagnosis of BHDS prior to genetic testing, indicating the importance of genetic testing in identifying these cases. The findings suggest that RCC may be less common in BHDS than previously thought.<br /><br />The study was conducted retrospectively, reviewing cases with FLCN variants identified through genetic testing. Clinical information and testing indication were extracted for some of the cases. The FLCN variants were classified using the ACMG/AMP guidelines.<br /><br />In conclusion, this case series demonstrates the phenotypic range of kidney disease features associated with BHDS and supports the idea that RCC may be less common in BHDS than previously believed. Genetic testing can be valuable in identifying BHDS cases that do not meet the clinical diagnostic criteria based on classic features.

Asset Subtitle

Submitter Only - Nour Baddar, PhD; Co-Author - Kathryn Curry, MS, CGC; Co-Author - Meg M. Hager, MS, MPH, CGC; Co-Author - Akash Anand, BS; Co-Author - Maggie Westermeyer, MS, CGC; Co-Author - Emily Hendricks, MS, CGC; Presenting Author - Tessa Pitman, MS, CGC; Co-Author - Kathleen Collett, MS, CGC; Co-Author - Quinn Stein, MS, CGC; Co-Author - Sumit Punj, PhD, FACMG;

Meta Tag

Genetic Testing

NextGen Sequencing

Phenotypic delineation of disorders

Variant Detection

Co-Author Kathryn Curry, MS, CGC

Co-Author Meg M. Hager, MS, MPH, CGC

Co-Author Akash Anand, BS

Co-Author Maggie Westermeyer, MS, CGC

Co-Author Emily Hendricks, MS, CGC

Co-Author Kathleen Collett, MS, CGC

Co-Author Quinn Stein, MS, CGC

Co-Author Sumit Punj, PhD, FACMG

Presenting Author Tessa Pitman, MS, CGC

Submitter Only Nour Baddar, PhD

Keywords

kidney disease phenotype

Birt-Hogg-Dubé syndrome

BHDS

pathogenic variants

folliculin gene

FLCN

chronic kidney disease

CKD

renal cell carcinoma

RCC