Balkan Journal of Medical Genetics

THE ROLE OF NEXT GENERATION SEQUENCING IN THE DIFFERENTIAL DIAGNOSIS OF CAROLI’S SYNDROME
Smolović B, Muhović D, Hodžić A, Bergant G, Peterlin B
*Corresponding Author: Professor Borut Peterlin, M.D., Ph.D., Department of Gynecology and Obstetrics, Institute of Medical Genetics, Department of Gynecology and Obstetrics, University Medical Centre Ljubljana, Šlajmerjeva Street 4, Ljubljana, Slovenia. Tel./Fax: +386-(0)1-540-1137. E-mail: borut.peterlin@guest.arnes.si
page: 49

INTRODUCTION

Caroli’s disease (CD) was first described by Jacques Caroli in 1958 [1], as a rare congenital condition characterized by localized or diffuse, non obstructive, saccular or fusiform, multifocal segmental dilatation of the intrahepatic bile ducts. The disease prevalence is one case per 1,000,000, however, with better imaging techniques, such as magnetic resonance cholangiography, CD appears to be more prevalent than previously reported [2,3]. Males and females are equally affected, and more than 80.0% of patients present before 30 years of age [4]. Recurrent cholangitis dominates the clinical course and is the principal cause of morbidity and mortality [5]. Two types of disease have been described: type 1, a simple form or CD without hepatic fibrosis and type 2, a complex form or Caroli’s syndrome (CS; also known as Grumbach’s disease) with the presence of congenital hepatic fibrosis (CHF) [3,6,7]. Caroli’s disease (type 1) consists of pure segmental cystic dilatations of the intrahepatic bile ducts, without cirrhosis and portal hypertension. Caroli’s disease can be diffuse, when it involves both lobes, or localized, when occuring in a single lobe. Increased incidence of biliary lithiasis, recurrent cholangitis, biliary abscesses and septicemia are all its potential complications [4,6]. Caroli’s syndrome (type 2) presents a clinical syndrome that is a combination of CD (bouts of cholangitis, hepatolithiasis, and gallbladder stones) and those of CHF (portal hypertension). Caroli’s syndrome is associated with hepatic fibrosis, or even cirrhosis, portal hypertension and oesophageal varices. Caroli’s syndrome may be accompanied by chol-angiocarcinoma, pancreatic cyst and renal cystic disease [4,6]. These diseases have a close relationship with congenital kidney disorders, notably autosomal recessive polycystic kidney disease (ARPKD) [8,9]. Many investigators believe that the two types of CD are actually different stages of the same disease characterized by periportal fibrosis and ductal dilatation [4,10]. Mutations in the polyductin 1 (PKHD1) gene, located on chromosome 6 (6p12.3-6p12.2), are responsible for CD, and many causative mutations are known [11-13]. Only a few of these variants in PKHD1 are responsible for ARPKD and CD, with a high interfamilial and intrafamilial phenotypic variability [9,11,12,]. We present a middle-aged patient, with very rare mutations in the PKHD1 gene, which led to CD with ARPKD that was, prior to NGS testing, misdiagnosed as primary sclerosing cholangitis (PSC).

Number 27 VOL. 27 (2), 2024	Number 27 VOL. 27 (1), 2024
Number 26 Number 26 VOL. 26(2), 2023 All in one	Number 26 VOL. 26(2), 2023
Number 26 VOL. 26, 2023 Supplement	Number 26 VOL. 26(1), 2023
Number 25 VOL. 25(2), 2022	Number 25 VOL. 25 (1), 2022
Number 24 VOL. 24(2), 2021	Number 24 VOL. 24(1), 2021
Number 23 VOL. 23(2), 2020	Number 22 VOL. 22(2), 2019
Number 22 VOL. 22(1), 2019	Number 22 VOL. 22, 2019 Supplement
Number 21 VOL. 21(2), 2018	Number 21 VOL. 21 (1), 2018
Number 21 VOL. 21, 2018 Supplement	Number 20 VOL. 20 (2), 2017
Number 20 VOL. 20 (1), 2017	Number 19 VOL. 19 (2), 2016
Number 19 VOL. 19 (1), 2016	Number 18 VOL. 18 (2), 2015
Number 18 VOL. 18 (1), 2015	Number 17 VOL. 17 (2), 2014
Number 17 VOL. 17 (1), 2014	Number 16 VOL. 16 (2), 2013
Number 16 VOL. 16 (1), 2013	Number 15 VOL. 15 (2), 2012
Number 15 VOL. 15, 2012 Supplement	Number 15 Vol. 15 (1), 2012
Number 14 14 - Vol. 14 (2), 2011	Number 14 The 9th Balkan Congress of Medical Genetics
Number 14 14 - Vol. 14 (1), 2011	Number 13 Vol. 13 (2), 2010
Number 13 Vol.13 (1), 2010	Number 12 Vol.12 (2), 2009
Number 12 Vol.12 (1), 2009	Number 11 Vol.11 (2),2008
Number 11 Vol.11 (1),2008	Number 10 Vol.10 (2), 2007
Number 10 10 (1),2007	Number 9 1&2, 2006
Number 9 3&4, 2006	Number 8 1&2, 2005
Number 8 3&4, 2004	Number 7 1&2, 2004
Number 6 3&4, 2003	Number 6 1&2, 2003
Number 5 3&4, 2002	Number 5 1&2, 2002
Number 4 Vol.3 (4), 2000	Number 4 Vol.2 (4), 1999
Number 4 Vol.1 (4), 1998	Number 4 3&4, 2001
Number 4 1&2, 2001	Number 3 Vol.3 (3), 2000
Number 3 Vol.2 (3), 1999	Number 3 Vol.1 (3), 1998
Number 2 Vol.3(2), 2000	Number 2 Vol.1 (2), 1998
Number 2 Vol.2 (2), 1999	Number 1 Vol.3 (1), 2000
Number 1 Vol.2 (1), 1999	Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact