Primary cilia are important in development and maintenance of bile ducts [Masyuk et al., 2009
] and renal tubules [Masyuk et al., 2009
; Yoder 2007
]; hence, hepatorenal fibrocystic disease is a common manifestation of various ciliopathies [Gunay-Aygun, 2009
; Gunay-Aygun, 2008
]. The recent recognition that OFD I is a ciliopathy [Macco and Franco, 2009] makes it easier to understand why this multiple congenital anomaly syndrome is associated with the seemingly unrelated features of fibrocystic disease of kidneys, liver and pancreas.
Both of our OFD 1 patients had increased echogenicity of the liver on ultrasound, intact hepatocelluar function with normal or minimally elevated liver enzymes, and an enlarged left lobe of the liver that was palpable under the xiphoid while the right lobe was non-palpable at the costal margin. These finding are typical for CHF caused by various ciliary defects such as ARPKD and some cases with JSRD, especially the COACH syndrome [Callier et al., 2008
; Desmet, 1998
; Gunay-Aygun, 2009
; Gunay-Aygun 2008
; Kerr et al., 1978
]. CHF in ARPKD and COACH syndrome typically results in portal hypertension manifested with splenomegaly, often starting in childhood and worsening as patients get older [Gunay-Aygun 2009
; Kerr et al., 1978
]. In contrast, our two OFD1 patients had normal sized spleens and none of the other 33 patients in had splenomegaly, suggesting that CHF in OFD 1 is not typically associated with portal hypertension.
With regard to macroscopic biliary abnormalities, both our patients had strikingly similar beaded cystic dilatations of the intrahepatic biliary structures particularly around the porta hepatis. Whether this type of biliary abnormality is typical for OFD1-associated liver disease or not will be determined as more OFD I patients undergo MRCP.
Pancreatic cystic disease in Patient 1 was asymptomatic without any pain. Amylase and lipase were normal and she had no evidence for malabsorption or diabetes to suggest overt exocrine or endocrine pancreas dysfunction. Similarly, none of the reported cases with pancreas cysts had symptoms to suggest pancreas dysfunction. RHPD, another ciliopathy associated with pancreas involvement, results in pancreatic dysplasia in addition to macrocysts. Pancreas microscopy, reported in 3 OFD I cases (, Patient no 4, 14 and 19) did not reveal dysplasia.
Our patients were diagnosed with OFD I in the first year of life based on their characteristic facial and digital anomalies. However, the possibility of hepatic, pancreatic or renal involvement in OFD I was not pursued. For Patient 1, the consideration of a potential malignant pancreatic lesion may have led to unnecessary invasive evaluations and caused anxiety. In addition, she probably had hypertension for several years prior to its diagnosis at age 29, so she likely suffered systemic vascular damage. Similarly, the PKD and associated renal insufficiency of Patient 2 were not diagnosed until she approached end-stage kidney disease, preventing her from receiving appropriate supportive treatment.
OFD I patients are not aware of, or evaluated for, their risk of developing hepatic, renal and pancreatic fibrocystic disease. A significant proportion of patients are not even evaluated and monitored for PKD, the better recognized visceral involvement in OFD I [Prattichizzo et al., 2008
; Saal et al., 2010
; Szeto et al., 1977
; Thauvin-Robinet et al., 2006
]. In their report of OFD1
mutation analysis in 100 unrelated OFD I patients, Prattichizzo et al [Prattichizzo et al., 2008
], found that only 40 of 81 patients (49%) had renal imaging; 24 of these 40 (60%) had PKD. In the series reported by Thauvin-Robinet et al., the kidneys were not assessed in 36% (9 of 25) of the patients [Thauvin-Robinet et al., 2006
]. The proportion of OFD I patients who undergo imaging for liver and pancreas involvement is even smaller. Only 44% of the 34 patients reported by Saal et al. 
had their liver and pancreas evaluated. In the series of Prattichizzo et al.[Prattichizzo et al., 2008
], four patients were reported as having pancreatic, hepatic, and/or ovarian cysts; the number of patients who had liver and pancreas imaging was not given.
OFD I patients with less obvious craniofacial features can escape the diagnosis of OFD I, and instead present to nephrology clinics in adulthood with late manifestations of PKD; they are often diagnosed with autosomal dominant polycytsic kidney disease (ADPKD). Eight of 33 patients in our literaure review (24%) were diagnosed with OFD I only after presenting with PKD. Two features that are potentially helpful to distinguish X-linked OFD I-related PKD from ADPKD are the presence of affected females only, in multiple generations and preserved renal contour.
Early diagnosis of the visceral manifestations of OFD I is essential for anticipatory care and prevention of hepatic, pancreatic and renal complications. Timely diagnosis and understanding of the fibrocystic nature of the hepatorenal and pancreatic disease in this condition may also prevent unnecessary and invasive diagnostic and therapautic interventions.