Neuroradiologic, Clinical, and Genetic Characterization of Cerebellar Heterotopia: A Pediatric Multicentric Study

Ludovica Pasca; Filippo Arrigoni; Romina Romaniello; Maria Savina Severino; Davide Politano; Fulvio D'Abrusco; Jessica Garau; Valentina De Giorgis; Adriana Carpani; Sabrina Signorini; Simona Orcesi; Felice D'Arco; Enrico Alfei; Elisa Cattaneo; Elisa Rognone; Sara Uccella; Maria Teresa Divizia; Paolo Infantino; Enza Maria Valente; Renato Borgatti; Anna Pichiecchio

doi:10.3174/ajnr.A8450

Neuroradiologic, Clinical, and Genetic Characterization of Cerebellar Heterotopia: A Pediatric Multicentric Study

AJNR Am J Neuroradiol. 2024 Dec 27. doi: 10.3174/ajnr.A8450. Online ahead of print.

Authors

Ludovica Pasca^{1

2}, Filippo Arrigoni³, Romina Romaniello⁴, Maria Savina Severino^{5

6}, Davide Politano^{1

2}, Fulvio D'Abrusco^{1

7}, Jessica Garau⁸, Valentina De Giorgis^{1

2}, Adriana Carpani², Sabrina Signorini², Simona Orcesi^{1

2}, Felice D'Arco⁹, Enrico Alfei¹⁰, Elisa Cattaneo¹¹, Elisa Rognone¹², Sara Uccella¹³, Maria Teresa Divizia¹⁴, Paolo Infantino^{14

15}, Enza Maria Valente^{1

7

8}, Renato Borgatti^{1

2}, Anna Pichiecchio^{1

12}

Affiliations

¹ From the Departments of Brain and Behavioral Sciences (L.P., D.P., V.D.G., S.O., R.B., A.P.), and Molecular Medicine (F.D., E.M.V.), University of Pavia, Pavia, Italy.
² Child Neurology and Psychiatry Unit (L.P., R.R., D.P., V.D.G., A.C., S.S., S.O., R.B.), IRCCS Mondino Foundation, Pavia, Italy.
³ Radiology and Neuroradiology Department (F.A.), Vittore Buzzi Children's Hospital, Milan, Italy.
⁴ Child Neurology and Psychiatry Unit (L.P., R.R., D.P., V.D.G., A.C., S.S., S.O., R.B.), IRCCS Mondino Foundation, Pavia, Italy [email protected].
⁵ Neuroradiology Unit (M.S.S.), IRCCS Istituto Giannina Gaslini, Genova, Italy.
⁶ Neuroradiology Unit (M.S.S.), Child Neuropsychiatry Unit (S.U.), IRCCS Istituto Giannina Gaslini, Genoa, Italy.
⁷ Department of Molecular Medicine (F.D., E.M.V.), University of Pavia, Pavia, Italy.
⁸ Neurogenetics Research Center (J.G., E.M.V.), IRCCS Mondino Foundation, Pavia, Italy.
⁹ Department of Radiology (F.D.), Neuroradiology Unit, Great Ormond Street Hospital for Children, London, United Kingdom.
¹⁰ Pediatric Neurology Unit (E.A.), and Department of Pediatrics, Vittore Buzzi Children's Hospital, Milan, Italy.
¹¹ Clinical Genetics Unit (E.C.), Department of Pediatrics, Vittore Buzzi Children's Hospital, Milan, Italy.
¹² Department of Neuroradiology (E.R., A.P.), Advanced Imaging and Radiomics Center, IRCCS Mondino Foundation, Pavia, Italy.
¹³ Department of Neurosciences (S.U.), Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
¹⁴ Genomics and Clinical Genetics Unit (M.T.D., P.I.), IRCCS Istituto Giannina Gaslini, Genoa, Italy.
¹⁵ Università degli Studi di Genova (P.I.), Genoa, Italy.

PMID: 39406511
DOI: 10.3174/ajnr.A8450

Abstract

Background and purpose: Cerebellar heterotopia (CH) is a neuroradiologic abnormality that is poorly reported and investigated in the literature. It can be observed as an isolated finding, but it has been mainly reported in the context of cerebellar dysgenesis and syndromic conditions. This study aims to provide a comprehensive neuroradiologic, clinical, and genetic characterization of a cohort of pediatric patients with CH.

Materials and methods: Patients with a diagnosis of CH were systematically selected from the neuroimaging databases of the 4 Italian centers participating in this retrospective study. For each patient, information regarding demographic, clinical, genetic, and neuroradiologic data was collected.

Results: Thirty-two pediatric patients were recruited and subdivided into 2 groups: patients with isolated CH and/or cerebellar malformations (n = 18) and patients with CH associated with cerebral malformations (n = 14). Isolated CH consistently showed a peripheral subcortical localization in the inferior portion of cerebellar hemispheres, with either unilateral or bilateral distribution. Ten patients belonging to the second group had a diagnosis of CHARGE syndrome, and their nodules of CH were mainly but not exclusively bilateral, symmetric, located in the peripheral subcortical zone and the inferior portion of the cerebellar hemispheres. The remaining 4 patients of the second group showed either bilateral or unilateral CH, located in both the peripheral cortex and deep white matter and the superior and inferior portions of cerebellum. Patients with isolated CH showed a high prevalence of language development delay; neurodevelopmental disorders were the most represented clinical diagnoses. Recurring features were behavioral problems and motor difficulties. A conclusive genetic diagnosis was found in 18/32 patients.

Conclusions: We found distinctive neuroradiologic patterns of CH. Genetic results raise the possibility of a correlation between cerebellar morphologic and functional developmental disruption, underscoring the importance of CH detection and reporting to orient the diagnostic path.