Kidney Week

Abstract: SA-PO594

Oral-Facial-Digital Syndrome Type 1: An Underestimated Differential Diagnosis of PKD in Women

Session Information

• Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Wolff, Constantin Aaron, Klinik m. S. Nephrologie und internistische Intensivmedizin, Charité - Universitätsmedizin, Berlin, Germany

Constantin Aaron Wolff

• Audrezet, Marie-Pierre, Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest and INSERM UMR1078, Brest, France

Marie-Pierre Audrezet, PhD

• Cornec-Le Gall, Emilie, Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest and INSERM UMR1078, Brest, France

Emilie Cornec-Le Gall, MD, PhD

• Halbritter, Jan, Klinik m. S. Nephrologie und internistische Intensivmedizin, Charité - Universitätsmedizin, Berlin, Germany

Jan Halbritter, MD

Group or Team Name

• AG Halbritter, AG Cornec-Le Gall.

Background

OFD1 (oral-facial-digital syndrome type 1) is an X-linked inherited multi-systemic disorder with variable presentation. Although first identified in 2001, little is known about the true prevalence, natural course, and outcomes of OFD1-related kidney disease. With this case series, we aim to highlight OFD1-related kidney disease as an underestimated phenocopy of autosomal-dominant polycystic kidney disease (ADPKD) in women.

Methods

We performed a retrospective study of patients with a genetically confirmed OFD1 diagnosis who presented to multiple centers in European renal clinics between 2006 and 2024. We collected demographic, clinical, laboratory, imaging, and histopathological data for statistical analysis.

Results

We identified 19 females from 15 families with OFD1-related kidney disease (mean age: 54y ± 4y). The median age at diagnosis was 38y ± 4y. Erroneously 11 patients were classified as typical ADPKD, and partially treated with tolvaptan (n=6). Genetically, all patients harbored monoallelic truncating variants N-terminal of the SDCCAG8-interaction domain (Fig.1). Phenotypically, all patients presented with majorly non-enlarged PKD. Estimated glomerular filtration rate varied widely and showed no overall trend even within families and age groups. Eight patients developed kidney failure (KF) at a mean age of 47.5 years. In addition to PKD, typical extra-renal features (e.g. frenulum, syndactyly, epilepsy, cleft lip and palate, intellectual disability) were observed in 11 patients (58%) to variable degrees.

Conclusion

Our study highlights the importance of considering OFD1 in the differential diagnosis of normal-sized PKD with or without further extra-renal abnormalities, particularly in young females. Early detection and timely initiation of general kidney protection measures may improve treatment outcomes and delay progression to KF. Further studies are required to evaluate specific treatment options for OFD1-related PKD, as the benefit of otherwise licensed tolvaptan has not been demonstrated.

Fig.1: A modified protein structure of OFD1 with patient variants.