Prenatal Diagnosis of Joubert Syndrome 23 With Left Isomerism: A Novel Phenotype Associated With Pathogenic KIAA0586...

Joubert syndrome is a rare autosomal recessive ciliopathy defined by the "molar tooth" sign caused by cerebellar vermis hypoplasia and abnormal superior cerebellar peduncles. Over 40 genes are known to cause the disorder, including KIAA0586, which encodes the centrosomal protein TALPID3, essential for ciliogenesis and Hedgehog signaling. Although KIAA0586-related Joubert syndrome is primarily neurodevelopmental, cilia also play a key role in left-right axis formation, however, laterality defects have not been reported in this context. We describe a prenatal case with suspected Joubert syndrome and left isomerism carrying a homozygous likely pathogenic KIAA0586 frameshift variant. The fetus showed dextrocardia, azygos continuation of the inferior vena cava, median gallbladder, persistent right umbilical vein, and a suspected molar tooth sign. This case suggests a possible phenotypic expansion of KIAA0586-related ciliopathy and supports a role for TALPID3 in human left-right patterning.