Fibrocystic disease of liver and pancreas; under-recognized features of the X-linked ciliopathy oral-facial-digital syndrome type 1 (OFD I).
OFD I is an X-linked dominant male-lethal ciliopathy characterized by prominent external features including oral clefts, hamartomas or cysts of the tongue, and digital anomalies. Although these external features are easy to recognize and often lead to diagnosis in early childhood, visceral findings in OFD I, especially the fibrocystic liver and pancreas disease, are under-recognized. In addition, while the occurrence of polycystic kidney disease (PKD) in OFD I is well known, few patients are evaluated and monitored for this complication. We report on two adult females diagnosed with OFD I in infancy, but not evaluated for visceral involvement. In adulthood, they were incidentally found to have severe hypertension and chronic renal insufficiency due to undiagnosed PKD. A pancreatic cystic lesion, also discovered incidentally, was thought to be malignant and led to consideration of major surgery. We present NIH evaluations, including documentation of OFD I mutations, extreme beading of the intrahepatic bile ducts, pancreatic cysts, and tabulate features of reported OFD I cases having hepatic, pancreatic, and renal cystic disease. Liver and pancreas are not routinely evaluated in OFD I patients. Increased awareness and lifelong monitoring of visceral complications, particularly involving the liver, pancreas, and kidney, are essential for timely and accurate treatment.
Chetty-John
Shilpa
S
NIH-NHGRI, Medical Genetics Branch, Bethesda, Maryland 20892, USA.
Piwnica-Worms
Katie
K
Bryant
Joy
J
Bernardini
Isa
I
Fischer
Roxanne E
RE
Heller
Theo
T
Gahl
William A
WA
Gunay-Aygun
Meral
M
D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014059:Tongue / Q000002:abnormalities
C115130:OFD1 protein, human; D011506:Proteins
Curr Opin Gastroenterol. 2009 May;25(3):265-71
19349863
Ann Intern Med. 1977 Jun;86(6):738-41
869353
Ann Genet. 2002 Apr-Jun;45(2):59-62
12119212
Am J Kidney Dis. 1982 Mar;1(5):288-93
7072712
Hum Mutat. 2008 Oct;29(10):1237-46
18546297
Z Kinderheilkd. 1972;112(1):89-112
4336265
Hum Mol Genet. 1997 Jul;6(7):1163-7
9215688
Nephrol Dial Transplant. 1997 May;12(5):1040-2
9175067
Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):296-306
19876928
Clin Genet. 2010 Mar;77(3):258-65
19817772
Revue Stomatol. 1954 Apr;55(4):209-27
15444577
Am J Med Genet. 1987 Feb;26(2):391-403
3812591
J Med Genet. 2006 Jan;43(1):54-61
16397067
Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93
17955020
Nephrol Dial Transplant. 2006 Jun;21(6):1705-9
16384823
Clin J Am Soc Nephrol. 2007 Jan;2(1):38-45
17699385
J Am Soc Nephrol. 2007 May;18(5):1381-8
17429051
N Engl J Med. 1964 Nov 19;271:1073-8
14210999
Nephrol Dial Transplant. 2000 Aug;15(8):1245-7
10910455
Contrib Nephrol. 1997;122:58-60
9399040
J Med Genet. 1987 Feb;24(2):116-8
3560170
Urol Radiol. 1992;13(3):153-7
1539404
J Pediatr. 1962 Oct;61:520-30
13900550
Am J Med Genet. 1998 Feb 3;75(4):389-94
9482645
N Engl J Med. 2006 May 18;354(20):2122-30
16707749
Am J Med Genet. 1991 Mar 15;38(4):574-82
2063902
Nephrol Dial Transplant. 1998 Mar;13(3):763-6
9550664
Arch Pathol Lab Med. 1991 May;115(5):519-23
2021323
J Med Genet. 1987 Feb;24(2):84-7
3560172
Mayo Clin Proc. 1998 Jan;73(1):80-9
9443684
Clin Genet. 1976 Feb;9(2):183-6
1248177
Am J Med Genet A. 2008 Aug 15;146A(16):2109-15
18629884
Gut. 1978 Jun;19(6):514-20
680586