A CSPP1 variant associated with metabolic dysfunction in Joubert syndrome: a case report.

Background: Joubert syndrome is a genetically heterogeneous ciliopathy characterized by cerebellar vermis hypoplasia and the distinctive molar tooth sign on neuroimaging, often accompanied by neurological impairment. Pathogenic CSPP1 variants account for approximately 3% of Joubert syndrome cases. While certain ciliopathies have been associated with metabolic dysfunction, this has not been described in CSPP1-related Joubert syndrome.

Case presentation: We report a 16-year-old Honduran mestiza female patient with CSPP1-related Joubert syndrome who presented with insulin resistance, early onset diabetes, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease. Notably, she lacked the typical neurological symptoms of Joubert syndrome. Brain magnetic resonance imaging revealed cerebellar vermis hypoplasia, confirming the diagnosis. Genetic testing identified a pathogenic heterozygous CSPP1 variant (c.3052C > T, p.Gln1018), supporting the diagnosis of CSPP1-related Joubert syndrome.

Conclusion: This case expands the phenotypic spectrum of CSPP1-related Joubert syndrome and raises the possibility of a role for CSPP1 in metabolic homeostasis. Further research is needed to determine whether CSPP1 mutations contribute to metabolic dysfunction via ciliary or centrosome-associated mechanisms.