Cerebellar hypoplasia: Differential diagnosis and diagnostic approach

Abstract

Cerebellar hypoplasia (CH) refers to a cerebellum with a reduced volume, and is a common, but non-specific neuroimaging finding. The etiological spectrum of CH is wide and includes both primary (malformative) and secondary (disruptive) conditions. Primary conditions include chromosomal aberrations (e.g., trisomy 13 and 18), metabolic disorders (e.g., molybdenum cofactor deficiency, Smith-Lemli-Opitz syndrome, and adenylosuccinase deficiency), genetic syndromes (e.g., Ritscher-Schinzel, Joubert, and CHARGE syndromes), and brain malformations (primary posterior fossa malformations e.g., Dandy-Walker malformation, pontine tegmental cap dysplasia and rhombencephalosynapsis, or global brain malformations such as tubulinopathies and α-dystroglycanopathies). Secondary (disruptive) conditions include prenatal infections (e.g., cytomegalovirus), exposure to teratogens, and extreme prematurity. The distinction between malformations and disruptions is important for pathogenesis and genetic counseling. Neuroimaging provides key information to categorize CH based on the pattern of involvement: unilateral CH, CH with mainly vermis involvement, global CH with involvement of both vermis and hemispheres, and pontocerebellar hypoplasia. The category of CH, associated neuroimaging findings and clinical features may suggest a specific disorder or help plan further investigations and interpret their results. Over the past decade, advances in neuroimaging and genetic testing have greatly improved clinical diagnosis, diagnostic testing, recurrence risk counseling, and information about prognosis for patients and their families. In the next decade, these advances will be translated into deeper understanding of these disorders and more specific treatments.

Hipoplasia pontocerebelosa secundaria a deleción en el gen CASK: Caso clínico

“…Regarding our clinical case, it was observed this retardation, which was actually the symptom that alerted the parents and their pediatrician. In addition, they may develop ataxia, altered eye movements, dysarthria, intentional tremor, convulsions, intellectual disability, dyskinesia and choreic movements 1,3 . In our clinical case, we could observe that progressively appeared convulsions and intellectual disability, without observing abnormal eye movements, trembling or choreic movements.…”

“…Also, we could include genetic alterations: mutations in the CASK gene, cerebellar agenesis secondary to mutations in PTF1A, -dystroglicopathies such as Walker-Warburg Syndrome, Musculoskeletal Disease or Fukuyama Disease, posterior fossa malformations such as pontine tegmento dysplasia and structural lesions, as cerebellar agenesis or cerebellar damage secondary to prematurity (eg. Johnsen-TarbyLewis syndrome) 1,3 . With regard to genetic alterations, CASK gene mutations related to this disorder have been described.…”

“…Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative diseases with a genetic origin, from which only 10 subtypes are known (PCH [1][2][3][4][5][6][7][8][9][10]. The term PCH is used generically to describe a size reduction of the cerebellum and also the protuberance.…”

“…The term PCH is used generically to describe a size reduction of the cerebellum and also the protuberance. According to entities, in addition to the aforementioned ones, there are other entities with PCH that may also be included, such as cortical malformations, metabolic diseases and genetic diseases [1][2][3] . Patients with cerebellar hypoplasia usually present muscular hypotonia and a delayed cognitive development, from moderate to severe.…”

“…Patients with cerebellar hypoplasia usually present muscular hypotonia and a delayed cognitive development, from moderate to severe. They may also develop ataxia, altered eye movements, dysarthria, intentional tremor, seizures and other neurological symptoms 1,3 . Regarding the genetic etiology, mutations in the CASK gene related to this disorder have been described.…”