Rotor Syndrome

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].

Excerpt

Clinical characteristics: Rotor syndrome is characterized by mild conjugated and unconjugated hyperbilirubinemia that usually begins shortly after birth or in childhood. Jaundice may be intermittent. Conjunctival icterus may be the only clinical manifestation.

Diagnosis/testing: The diagnosis of Rotor syndrome is established in a proband with isolated, predominantly conjugated hyperbilirubinemia without cholestasis or liver injury and typical findings on cholescintigraphy. Identification of biallelic pathogenic variants in SLCO1B1 and SLCO1B3 on molecular genetic testing can confirm the diagnosis when cholescintigraphy is either not available or not recommended due to risks associated with the procedure.

Management: Treatment of manifestations: No treatment required.

Agents/circumstances to avoid: Although no adverse drug effects have been documented in persons with Rotor syndrome, the absence of the hepatic proteins OATP1B1 and OATP1B3 may have serious consequences for liver uptake – and thus for the toxicity of numerous commonly used drugs and/or their metabolites.

Other: Because most individuals with Rotor syndrome are born to consanguineous couples, the diagnosis of Rotor syndrome may coincidentally identify such consanguinity. In some centers, this may be an indication for clinical genetics consultation and/or genetic counseling.

Genetic counseling: Rotor syndrome is inherited in an autosomal recessive digenic manner. The parents of an affected child are obligate heterozygotes for a pathogenic variant in SLCO1B1 and a pathogenic variant in SLCO1B3 or obligate heterozygotes for a large deletion affecting the coding regions of both SLCO1B1 and SLCO1B3. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier of at least one pathogenic variant, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible if the pathogenic variants have been identified in an affected family member.

Publication types

  • Review