Phenotypic Spectrum and Natural History of Gillespie Syndrome. An Updated Literature Review with 2 New Cases

• Published in: Cerebellum (London, England) Vol. 23; no. 6; pp. 2655 - 2670
• Main Authors: Ciaccio, Claudia, Taddei, Matilde, Pantaleoni, Chiara, Grisoli, Marina, Di Bella, Daniela, Magri, Stefania, Taroni, Franco, D’Arrigo, Stefano
• Format: Journal Article
• Language: English
• Published: New York Springer US 23-08-2024; Springer Nature B.V
• Subjects: Amino acids; Aniridia; Ataxia; Atrophy; Biomedical and Life Sciences; Biomedicine; Case Report; Cerebellar ataxia; Cerebellum; Comorbidity; Intellectual disabilities; Literature reviews; Neurobiology; Neurology; Neurosciences; Congenital ataxia; Gillespie; Cerebellar ataxia; Aniridia; ITPR1
• ISSN: 1473-4230; 1473-4222; 1473-4230
• DOI: 10.1007/s12311-024-01733-7

Background
Gillespie syndrome is a rare disorder caused by pathogenic variants in
ITPR1
gene and characterized by the typical association of cerebellar ataxia, bilateral aniridia and intellectual disability. Since its first description in 1965, less than 100 patients have been reported and only 30 with a molecular confirmation.
Methods
We present two additional cases, both carrying a loss-of-function variant in the Gly2539 amino acid residue. We describe the clinical evolution of the patients, one of whom is now 17 years old, and discuss the updated phenotypic spectrum of the disorder.
Results
The study gives an overview on the condition, allowing to confirm important data, such as an overall positive evolution of development (with some patient not presenting intellectual disability), a clinical stability of the neurological signs (regardless of a possible progression of cerebellar atrophy) and ocular aspects, and a low prevalence of general health comorbidities.
Discussion
Data about development and the observation of middle-aged patients lend support to the view that Gillespie is to be considered a non-progressive cerebellar ataxia, making this concept a key point for both clinicians and therapists, and for the families.