A recent NIH study (A Strongin et al. JPGN 2018; 66: 428-35) provides prospectively-collected data from 100 individuals (mean age 9.1 years) with Joubert syndrome (JS). ( of the patients were >20 years old.
Background: JS is classified as a ciliopathy as mutations in JS genes result in nonmotile cilia. Clinical features in this autosomal recessive condition include the following:
- MRI finding of a “molar tooth sign” caused by cerebellar vermis hypoplasia, horizontally-oriented cerbellar peducles, and a deep interpeduncular fossa
- Ocular features: retinal dystrophy, colobomas
- Renal: nephronophthisis, polycystic kidneys
- Skeletal abnormalities including polydactaly
- Hepatic: congenital hepatic fibrosis (CHF). CHF typically causes noncirrhotic portal hypertension and generally maintain synthetic function and do not progress to cirrhosis
Study Key Findings:
- 43 (43%) had liver involvement indicated by elevated liver enzymes, and/or liver hyperechogenicity and/or splenomegaly
- 13 (13%) developed probable portal hypertension; this group had more significant elevations in alkaline phosphatase (269 vs 169), ALT (92 vs 42), AST (77 vs 40) and GGT (226 vs 51)
- The portal hypertension group were much more likely to have TMEM67 gene mutation
- Probable portal hypertension was associated with renal involvement (P=0.001)
- None of the patients with JS had macrocystic liver disease (which likely indicates a low risk of cholangitis)
The authors note that previous estimates of liver disease with JS of 10-15% are likely an underestimate and that “hepatic disease becomes more noticeable later in life.” In their discussion, they describe the limitations of their study which includes ascertainment bias as their cohort may differ significantly from those who have not bee brought to the attention of the NIH.
My take: JS patients are at increased risk for hepatic disease/portal hypertension, particularly at older ages. The optimal surveillance strategy remains undefined.
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