Clinical Features and Revised Diagnostic Criteria in Joubert Syndrome

Abstract

The clinical presentation of children with Joubert syndrome can include nonspecific features such as hypotonia, ataxia, and developmental delay. Careful examination of the face shows a characteristic appearance, and a neuro-ophthalmologic examination shows the presence of oculomotor apraxia. In the neonatal period, most children have hyperpnea intermixed with central apnea. Neuroimaging of the head in the axial plane demonstrates the "molar tooth sign"--deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis. The central nervous system malformation spectrum observed in radiologic and neuropathologic studies accounts for many clinical features of Joubert syndrome. The developmental delay and cognitive impairment cannot be fully explained by the hindbrain malformation and probably result from dysfunction of the cerebral hemispheres. Although related conditions with vermian hypoplasia or aplasia (including Arima; Senior-Loken; and cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndromes) can mimic Joubert syndrome, detailed imaging data are lacking in such cases. We propose a revision in diagnostic criteria for Joubert syndrome.

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome

“…All magnetic resonance images (MRIs; or computed tomography scans) of affected individuals were read by multiple neurologists and Joubert syndrome was diagnosed using previously described criteria 2,9,26,27 . Clinical features of children with Joubert syndrome include an inability to walk due to severe clumsiness, oculomotor abnormalities, hypotonia, ataxia, developmental delay with mental retardation, and mirror movements.…”

Cerebellar development and disease

“…The signature feature of this group of disorders is the "molar tooth" sign. This sign is a specific malformation of the brainstem, cerebellum and the cerebellar peduncles, which together, give the appearance of a tooth-like shape in axial MRI images at the level of the midbrain-hindbrain junction (isthmus) [26]. (Figure 2).…”

Cerebellar vermis hypoplasia - non progressive congenital ataxia: clinical and radiological findings in a pair of siblings

“…Many authors had recently published criteria for the diagnosis of Joubert syndrome, as Sztriha et al 20 and Maria et al 21 . The last one included common abnormalities characterized by hypotonia present in all patients, developmental delay including motor, language and adaptative behaviors, and many children are pleasant and friendly.…”