Superior Cerebellar Atrophy: An Imaging Clue to Diagnose ITPR1-Related Disorders

• Published in: International journal of molecular sciences Vol. 23; no. 12; p. 6723
• Main Authors: Romaniello, Romina, Pasca, Ludovica, Panzeri, Elena, D’Abrusco, Fulvio, Travaglini, Lorena, Serpieri, Valentina, Signorini, Sabrina, Aiello, Chiara, Bertini, Enrico, Bassi, Maria Teresa, Valente, Enza Maria, Zanni, Ginevra, Borgatti, Renato, Arrigoni, Filippo
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 16-06-2022; MDPI
• Subjects: Age; Ataxia; Atrophy; Calcium (intracellular); Calcium ions; cerebellar atrophy; Cerebellum; Genotype & phenotype; Hypoplasia; Inositol 1,4,5-trisphosphate receptors; Inositols; Magnetic resonance imaging; Medical imaging; MRI; Neuroimaging; Patients; Pattern recognition; Purkinje cells; United States > US
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23126723

The inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene encodes an InsP3-gated calcium channel that modulates intracellular Ca2+ release and is particularly expressed in cerebellar Purkinje cells. Pathogenic variants in the ITPR1 gene are associated with different types of autosomal dominant spinocerebellar ataxia: SCA15 (adult onset), SCA29 (early-onset), and Gillespie syndrome. Cerebellar atrophy/hypoplasia is invariably detected, but a recognizable neuroradiological pattern has not been identified yet. With the aim of describing ITPR1-related neuroimaging findings, the brain MRI of 14 patients with ITPR1 variants (11 SCA29, 1 SCA15, and 2 Gillespie) were reviewed by expert neuroradiologists. To further evaluate the role of superior vermian and hemispheric cerebellar atrophy as a clue for the diagnosis of ITPR1-related conditions, the ITPR1 gene was sequenced in 5 patients with similar MRI pattern, detecting pathogenic variants in 4 of them. Considering the whole cohort, a distinctive neuroradiological pattern consisting in superior vermian and hemispheric cerebellar atrophy was identified in 83% patients with causative ITPR1 variants, suggesting this MRI finding could represent a hallmark for ITPR1-related disorders.