Anomalies of Midbrain Hindbrain Development: Midbrain Clefts, Cerebellar Nodular Heterotopia with Overlying Dysgenesis, Cerebellar Foliation Disorder, Pontine Tegmental Cap Dysplasia; Joubert Syndrome; Lhermitte Duclos Syndrome. Diagnosis, Classification and Rehabilitation Hypothesis

Ersilia Campo; Federica Dierna; Antonio Zanghì; Michele Vecchio; Stefania Salafia; Pietro Foti; Emanuele David; Giuseppe Belfiore; Salvatore Lavalle; Martino Ruggieri; Agata Polizzi

doi:10.1055/s-0044-1786789

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2024; 22(05): 387-395
DOI: 10.1055/s-0044-1786789

Review Article

Anomalies of Midbrain Hindbrain Development: Midbrain Clefts, Cerebellar Nodular Heterotopia with Overlying Dysgenesis, Cerebellar Foliation Disorder, Pontine Tegmental Cap Dysplasia; Joubert Syndrome; Lhermitte Duclos Syndrome. Diagnosis, Classification and Rehabilitation Hypothesis

Ersilia Campo

¹Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy

,

Federica Dierna

¹Pediatrics Postgraduate Residency Program, University of Catania, Catania, Italy

,

Antonio Zanghì

²Department of Medical and Surgical Sciences and Advanced Technologies, Research Center for Surgery of Complex Malformation Syndromes of Transition and Adulthood, University of Catania, Catania, Italy

,

Michele Vecchio

³Department of Biomedical and Biotechnological Sciences, Rehabilitation Unit, University of Catania, Catania, Italy

,

Stefania Salafia

⁴Unit of Pediatrics, Lentini Hospital, Lentini, Italy

,

Pietro Foti

⁵Department of Medical Surgical Sciences and Advanced Technologies, Unit of Radiology 1, University Hospital Policlinico “G. Rodolico-San Marco”, Catania, Italy

,

Emanuele David

⁵Department of Medical Surgical Sciences and Advanced Technologies, Unit of Radiology 1, University Hospital Policlinico “G. Rodolico-San Marco”, Catania, Italy

,

Giuseppe Belfiore

⁵Department of Medical Surgical Sciences and Advanced Technologies, Unit of Radiology 1, University Hospital Policlinico “G. Rodolico-San Marco”, Catania, Italy

,

Salvatore Lavalle

⁶Chair of Radiology, Department of Medicine and Surgery, Kore University, Enna, Italy

,

Martino Ruggieri

⁷Department of Clinical and Experimental Medicine, Unit of Clinical Pediatrics, University of Catania, Catania, Italy

,

Agata Polizzi

⁸Chair of Pediatrics, Department of Educational Sciences, Chair of Pediatrics, University of Catania, Catania, Italy

› Author Affiliations

Abstract

Midbrain and hindbrain (MBHB) malformations are a rare group of congenital abnormalities that involve the neural structure of the posterior cranial fossa, leading to significant causes of neurodevelopmental dysfunction. Recent advancements in genetic and neuroimaging technologies have significantly enhanced our understanding of these disorders. The integration of these advances has facilitated a systematic classification of these conditions. A basic understanding of MBHB embryology is fundamental in order to understand the malformations occurring in their structures: MBHB neurons are mainly generated in the neuroepithelium, lining the walls of the fourth ventricle. Moreover, the regional specificity of the neural tube is determined by a combination of transcription factors expressed, organizing the fate of the neighboring regions as well. Clinical features of MBHB malformations are typically nonspecific; some patients may be asymptomatic or may develop neurological symptoms including hypotonia, ataxia, abnormal eye movements, decreased visual attention, cranial nerve deficits, cognitive impairment, and psychiatric symptoms. Many malformations have been described. We proposed the description of some of them, reporting their main morphologic aspects, magnetic resonance imaging (MRI) peculiar signs and their clinical presentation. Midbrain clefts, for example, are malformations characterized by median separation in the ventral midbrain which involves a communication with the cerebral aqueduct giving a “keyhole” shape. Pontine tegmental cap dysplasia, instead, is a rare hindbrain malformation responsible for a nonprogressive neurological disorder and is described with hypoplastic flat ventral pons, hypoplasia of the middle cerebellar peduncles, and hypoplasia and malformation of the worm. Joubert syndrome, cerebellar nodular heterotopia, abnormal cerebellar foliation, and Lhermitte–Duclos disease, also called dysplastic cerebellar gangliocytoma, have been described as well in order to provide a general overview on this diagnostic challenge reporting the most recent findings.

Keywords

cerebellum - genetics - Joubert syndrome - Lhermitte–Duclos syndrome - patterning - neurons

Full Text

References

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