BACKGROUND: Oral-facial-digital syndrome type 1 (OFD1) is a rare disorder comprising malformations of the face, oral cavity, hands, and feet. Polycystic kidney disease (PKD) is a more recently recognized feature of the syndrome. SUBJECTS AND METHODS: We now report on the clinical, radiological and histopathological features of an OFD1 and PKD kindred with five affected members in three subsequent generations. RESULTS: All patients were female and had accompanying PKD as assessed by ultrasound scans. The plasma creatinine was normal in three, but PKD caused end-stage renal failure in two of these individuals in the second and fifth decades. A histochemical analysis of renal tissue from one affected member of this kindred demonstrated a predominantly glomerulocystic kidney disease with a minor population of cysts derived from distal tubules as assessed by staining with Arachis hypogaea lectin. Cyst epithelia had a high level of mitosis as assessed by staining with antisera to proliferating cell nuclear antigen, and distal cysts overexpressed PAX2 protein, a potentially oncogenic transcription factor. We detected multiple pancreatic cysts in one member affected by OFD1 although there were no symptoms of pancreatic disease; this constitutes a novel radiological feature of the syndrome. CONCLUSIONS: This kindred illustrates the inheritance pattern of OFD1 and its accompanying PKD. Although the renal disease superficially resembles ADPKD with macroscopic cysts and a dominant inheritance pattern, histology shows a predominance of glomerular cysts and the syndrome is X-linked, with affected males dying before birth. The recognition of the accompanying dysmorphic features is the key to a diagnosis of OFD1 in a female child or adult who presents with PKD.
BACKGROUND: Oral-facial-digital syndrome type 1 (OFD1) is a rare disorder comprising malformations of the face, oral cavity, hands, and feet. Polycystic kidney disease (PKD) is a more recently recognized feature of the syndrome. SUBJECTS AND METHODS: We now report on the clinical, radiological and histopathological features of an OFD1 and PKD kindred with five affected members in three subsequent generations. RESULTS: All patients were female and had accompanying PKD as assessed by ultrasound scans. The plasma creatinine was normal in three, but PKD caused end-stage renal failure in two of these individuals in the second and fifth decades. A histochemical analysis of renal tissue from one affected member of this kindred demonstrated a predominantly glomerulocystic kidney disease with a minor population of cysts derived from distal tubules as assessed by staining with Arachis hypogaea lectin. Cyst epithelia had a high level of mitosis as assessed by staining with antisera to proliferating cell nuclear antigen, and distal cysts overexpressed PAX2 protein, a potentially oncogenic transcription factor. We detected multiple pancreatic cysts in one member affected by OFD1 although there were no symptoms of pancreatic disease; this constitutes a novel radiological feature of the syndrome. CONCLUSIONS: This kindred illustrates the inheritance pattern of OFD1 and its accompanying PKD. Although the renal disease superficially resembles ADPKD with macroscopic cysts and a dominant inheritance pattern, histology shows a predominance of glomerular cysts and the syndrome is X-linked, with affected males dying before birth. The recognition of the accompanying dysmorphic features is the key to a diagnosis of OFD1 in a female child or adult who presents with PKD.
Authors: C Bingham; M P Bulman; S Ellard; L I Allen; G W Lipkin; W G Hoff; A S Woolf; G Rizzoni; G Novelli; A J Nicholls; A T Hattersley Journal: Am J Hum Genet Date: 2000-11-20 Impact factor: 11.025
Authors: Lani C Keller; Stefan Geimer; Edwin Romijn; John Yates; Ivan Zamora; Wallace F Marshall Journal: Mol Biol Cell Date: 2008-12-24 Impact factor: 4.138