Kidney Week

Abstract: TH-PO0134

Functional Kidney Disease Predominates in PTPN11-Associated Noonan Syndrome Identified Through Nephrology Practice

Session Information

• Integrative Genomics and Multi-Omics in Noncystic Genetic Kidney Disease
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Case, Nicholas R., Natera Inc, Austin, Texas, United States

Nicholas R. Case, MS

• Wollen, Hope Jordan Ann, Alberta Children's Hospital, Calgary, Alberta, Canada

Hope Jordan Ann Wollen, MSc

• Vance, Cassie, Natera Inc, Austin, Texas, United States

Cassie Vance

• Punj, Sumit, Natera Inc, Austin, Texas, United States

Sumit Punj, PhD

• Vincent, Lisa M., Natera Inc, Austin, Texas, United States

Lisa M. Vincent, PhD

• Baddar, Nour, Natera Inc, Austin, Texas, United States

Nour Baddar, PhD

• Westemeyer, Margaret, Natera Inc, Austin, Texas, United States

Margaret Westemeyer, MS

• Schneider, Ronen, Natera Inc, Austin, Texas, United States

Ronen Schneider, MD

• Stein, Quinn, Natera Inc, Austin, Texas, United States

Quinn Stein, MS

Background

Noonan syndrome (NS) is a genetic disorder characterized by dysmorphic facial features and heart defects, with renal involvement less commonly reported and typically structural. PTPN11 is the most frequently implicated gene in NS, and (likely) pathogenic (P/LP) variants are increasingly identified in patients without classic NS syndromic features. Here, we sought to define the renal phenotypic spectrum associated with PTPN11 P/LP variants in a nephrology-ascertained cohort.

Methods

We performed a retrospective analysis of patients tested with a broad kidney gene panel (the Renasight^TM test) with a P/LP variant in PTPN11. Clinical data including kidney function tests and ICD codes were collected. A provider questionnaire captured renal diagnoses, replacement therapy, and biopsy findings. Kidney phenotypes were categorized as functional or structural.

Results

Among 135,903 individuals tested, 43 had P/LP variants in PTPN11 (Age: 0-80 years old); of these, 15 (34.0%) had provider-completed questionnaires. Most patients (30/43; 69.8%) had kidney dysfunction including CKD (primarily stage 3) and/or abnormal kidney function markers (e.g., proteinuria). Structural kidney disease was uncommon (3/43; 7.0%) and more frequently seen at younger ages. A small number of patients (3/43; 7.0%) had no known kidney disease and were identified through living kidney donor evaluation or family history–based testing, with the remaining patients demonstrating mixed or incompletely characterized phenotypes. Notably, many patients presented primarily with kidney disease in the absence of typical NS features; 6 patients (14.0%) had an a priori NS diagnosis.

Conclusion

In this nephrology-ascertained cohort, P/LP variants in PTPN11 were more often associated with kidney dysfunction than with isolated structural abnormalities. Kidney predominant presentations may lack classic NS features and occur across a wide age range, including adulthood. Notably, genetic testing identified NS in patients without an a priori clinical diagnosis in most cases. Increased recognition of kidney involvement as part of PTPN11-associated disease may inform evaluation of unexplained CKD, inform broader evaluation for extra-renal manifestations, and support use of broad kidney panel testing.

Funding

• Commercial Support – Natera, Inc.