Objective: To describe the phenomenology and clinical course of movement disorders in CTNNB1-related neurodevelopmental disorder (CTNNB1-NDD).

Background: CTNNB1-NDD is a rare neurogenetic condition caused by loss-of-function variants in the CTNNB1 gene. Mild-to-severe intellectual disability is a constant finding, and exudative vitreoretinopathy affects up to 39% of affected individuals. A motor disorder featuring lower limbs spasticity is frequently encountered, and several reports described the possible occurrence of dystonia, ataxia and bradykinesia. However, detailed information about the phenotypic spectrum of movement disorders in CTNNB1-NDD are lacking.

Method: We prospectively assessed for movement disorders individuals with CTNNB1-NDD followed up at our Institution. Clinal, genetic and neuroimaging data were retrospectively reviewed.

Results: Ten out of 11 evaluated patients (6 females, age range 4-19 years) were found to have motor disorders. All patients had moderate or mild intellectual disability, and two patients showed autistic traits. All patients showed delayed motor development and one patient never reached autonomous walking. All 10 patient were found to have lower limbs hypertonia, and 9 showed broad based gait. However, only 3 patients showed pyramidal signs (Babinski or brisk reflexes), and no patients had overt weakness or ataxic features. Onset of gait disorder dated back to infancy in all cases. One patient had focal foot dystonia with onset in the school age. Two patients had multifocal dystonia, with cranio-cervical, oromandibular and upper limbs involvement and onset in the second decade, with one of them showing mild bradykinesia and exaggerated startle. These two latter patients were treated with a levodopa, and only one of them showed a clinical improvement.

Brain MRI was normal in 8 patients. One patient showed mild, non-specific white matter hyperintensity and one patient was found to have a calcification in the left caudate nucleus.

One patient underwent dopamine transporter (DaT) scan, that was normal.

Conclusion: Motor disorders are highly prevalent in CTNNB1-NDD. Gait abnormalities mainly consist in a recognizable, broad-based gait with (progressive) lower limbs hypertonia, in absence of overt ataxic or pyramidal signs and weakness. Dystonia can be encountered in adolescents, with prominent upper-body distribution. Dystonia responsiveness to L-DOPA is possible.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/movement-disorders-spectrum-in-ctnnb1-related-neurodevelopmental-disorders/