Phenotypic Spectrum of -Associated Joubert Syndrome: Possible Association with Esophageal Atresia and Review of the Literature.

Joubert syndrome (JS) is a multi-systemic ciliopathy, characterized by intellectual disability and congenital anomalies involving the brain, kidney, heart, and eye. Even if clinical presentation is variable, most authors consider a brain abnormality known as the molar tooth sign (MTS) as mandatory for diagnosis. About 40 genes were identified to be associated with JS, usually with an autosomal recessive pattern. variants represent a rare cause of JS; only six families were previously reported. We performed exome sequencing in a child with a syndromic phenotype, described the clinical features and molecular findings, and performed a review of the literature to identify known individuals with pathogenic variants in , highlighting clinical characteristics and gene-phenotype correlations. Using exome sequencing, we identified a homozygous novel frameshift variant c.808del, p.Ser270ValfsTer28 in in a 5-year-old male from a consanguineous family of Roma ethnic background. Notable clinical features of the proband include severe developmental delay, hypotonia, and post-axial polydactyly. He did not have MTS, but showed severe anemia and esophageal atresia, which was already reported in association with a variant. We collected the phenotypes of all reported patients and discussed common and distinct features with respect to typical JS. Affected individuals shared JS clinical features, although the typical MTS was not always present, polydactyly and renal abnormalities were absent, while pituitary abnormalities were common. Our report provides new data for -related JS, expanding the clinical phenotypic spectrum and suggesting a possible role of defects in the development of esophageal atresia.