ESPN 54th Annual Meeting

ESPN 2022


 
PHENOTYPE ANALYSIS OF A CILIOPATHY COHORT WITH DISEASE-CAUSING VARIANTS AND RENAL INVOLVEMENT: A RETROSPECTIVE SINGLE CENTER STUDY
Lisa-Marie Brislinger 1 Korbinian Maria Riedhammer 2 Aruna Marchetto 3 Moneef Shoukier 3 Peter Strotmann 4 Bärbel Lange-Sperandio 5 Velibor Tasic 6 Christian W. Schaaf 1 Roman Günthner 2 Jasima Comic 1 Julia Hoefele 1

1- Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
2- Department of Nephrology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany
3- Pränatal-Medizin München, Munich, Germany
4- Pediatric Nephrology, Childrens Hospital, München-Klinik Schwabing, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
5- Pediatric Nephrology, Dr. v. Hauner Childrens Hospital, Ludwig Maximilians University, Munich, Germany
6- University Children’s Hospital, Medical Faculty of Skopje, Skopje, Macedonia
 
Introduction:

Ciliopathies comprise a geno- and phenotypically complex and heterogeneous spectrum of syndromic or isolated disorders. The aim of this study was the retrospective analysis of the phenotype of individuals with disease-causing variants in ciliopathy-associated genes and renal involvement.

Material and methods:

The study included 69 individuals from 55 different families with a reported disease-causing variant in a ciliopathy-associated gene and an index individual with a renal phenotype. Data was collected using a standardized questionnaire. The reported variants were reviewed using the standards of the American College of Medical Genetics and current amendments. The cohort was divided into the following groups. 1.) postnatal disease onset vs. prenatal disease onset, and 2.) < 18 years at disease onset vs. ≥ 18 years at disease onset.

Results:

Individuals with disease onset < 18 years had a significantly lower median age at end-stage kidney disease than individuals ≥ 18 years (7 [IQR 3 - 11.5] years vs. 47 [31 - 64] years; p < 0.001). Furthermore, individuals with a prenatal onset of disease (24/69 individuals) vs. individuals with a postnatal onset of disease (45/69 individuals) showed a significantly higher risk for the development of extrarenal manifestations (OR = 6.9 [95% confidence interval 1.42 - 33.13]), a significantly higher risk of more than 2 extrarenal organ systems being involved (OR = 12.3 [3.46 - 43.59]), a central nervous system involvement (OR = 8.7 [2.36 - 31.93]) and skeletal anomalies (OR = 4.0 [1.14 - 14.09]).

Conclusions:

The results of this study help to improve human genetic counseling by emphasizing the increased probability of a syndromic disease and a more severe progression in early-onset ciliopathy disease. Especially in prenatal counseling, this should be taken into consideration.