ORAL-FACIAL-DIGITAL SYNDROME TYPE-1 IS ANOTHER DOMINANT POLYCYSTIC KIDNEY-DISEASE - CLINICAL, RADIOLOGICAL AND HISTOPATHOLOGICAL FEATURES OF A NEW KINDRED

Background. Oral-facial-digital syndrome type 1 (OFD1) is a rare disor der comprising malformations of the face, oral cavity, hands, and feet . Polycystic kidney disease (PKD) is a more recently recognized featur e of the syndrome. Subjects and methods. We now report on the clinical , radiological and histopathological features of an OFD1 and PKD kindr ed with five affected members in three subsequent generations. Results . All patients were female and had accompanying PKD as assessed by ult rasound scans. The plasma creatinine was normal in three, but PKD caus ed endstage renal failure in two of these individuals in the second an d fifth decades. A histochemical analysis of renal tissue from one aff ected member of this kindred demonstrated a predominantly glomerulocys tic kidney disease with a minor population of cysts derived from dista l tubules as assessed by staining with Arachis hypogaea lectin. Cyst e pithelia had a high level of mitosis as assessed by staining with anti sera to proliferating cell nuclear antigen, and distal cysts overexpre ssed PAX2 protein, a potentially oncogenic transcription factor. We de tected multiple pancreatic cysts in one member affected by OFD1 althou gh there were no symptoms of pancreatic disease; this constitutes a no vel radiological feature of the syndrome. Conclusions. This kindred il lustrates the inheritance pattern of OFD1 and its accompanying PKD. Al though the renal disease superficially resembles ADPKD with macroscopi c cysts and a dominant inheritance pattern, histology shows a predomin ance of glomerular cysts and the syndrome is X-linked, with affected m ales dying before birth. The recognition of the accompanying dysmorphi c features is the key to a diagnosis of OFD1 in a female child or adul t who presents with PKD.