Abstract: FR-PO306
Novel Renal Phenotype of a Rare Genetic Syndrome: Pericentrin (PCNT) Gene Related Microcephalic Osteodysplastic Primordial Dwarfism Type II
Session Information
- Genetic Diseases: Models, Mechanisms, Treatments
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Llanos, Maria, Cleveland Clinic, Cleveland, Ohio, United States
- Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States
- Herlitz, Leal C., Cleveland Clinic, Cleveland, Ohio, United States
- Shad, Fariha, Cleveland Clinic, Cleveland, Ohio, United States
- Hijazi, Fadi A., Cleveland Clinic, Cleveland, Ohio, United States
- Roberts, Mary-Beth, Cleveland Clinic, Cleveland, Ohio, United States
Group or Team Name
- Cleveland Clinic foundation
Introduction
Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is a rare genetic syndrome caused by bialleic mutations or deletions in the pericentrin gene (PCNT), characterized by short stature and microcephaly. Aside from its classic features, its association with vasculopathy including moyamoya disease has been increasingly recognized. CKD, renal artery stenosis and aneurysm have also been reported. However, the kidney histopathological data is limited. Here we report a patient who presented with proteinuric CKD, Moya Moya disease, microcephalic short stature and was found to have distinct and novel renal phenotype with endotheliopathy, and homozygous PCNT gene deletion.
Case Description
30 yr old male presented to renal genetics clinic due to CKD III, Moya Moya disease with multiple intracranial hemorrhages requiring multiple bypasses, hypertension, and family history of consanguinity and CKD in his mother and sisters. Exam was notable for short stature and microcephaly. He had estimated GFR of 36mL/min with a 1.2 UPCR. Serological work-up included negative ANA, DSDNA, ANCA, Hepatitis B, C antibody, HIV, lupus anticoagulant, monoclonals, anti-GBM, anti-MPO/PR3 antibodies and normal complements. Kidney biopsy demonstrated FSGS with endothelial abnormalities including mesangiolysis, segmental duplication of the GBMs, subendothelial widening and loss of endothelial fenestrations. Exome sequencing disclosed a pathogenic homozygous microdeletion on chromosome 21 involving multiple coding exons of the PCNT gene. This established the diagnosis of MOPDII. Familiar genetic testing was also offered. He was treated with Lisinopril with stable proteinuria and kidney function.
Discussion
The renal biopsy performed in this case highlighted the prominent endothelial injury in MOPDII related vasculopathy due to PCNT gene deletion. This expanded renal phenotype of MOPDII suggests that the vasculopathy observed with PCNT mutations may be related to endothelialopathy which deserves further investigation. This case also highlights the importance of genetic study in patients with systemic presentations and family history of kidney disease.