Movement disorder phenotype in CTNNB1-syndrome: A complex but recognizable phenomenology.

CTNNB1 gene loss-of-function variants cause Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, OMIM 615075). Although motor impairment represents a core feature of this condition, the motor phenotype remains poorly described. We systematically assessed a cohort of 14 patients with disease-causing CTNNB1 variants to better characterize the movement disorder phenotype. patients were enrolled at Bambino Gesù Children's Hospital in Rome, Italy, between January 2019 and February 2024. 14 participants were included and underwent extensive genetic and neurologic examination. Clinical features, neuroimaging and neurophysiological investigations were retrospectively analyzed from medical charts and video recordings. 13 out of 14 patients showed motor disorders (one only showing mild coordination difficulties). 12 presented abnormal gait (11 patients with broad-based gait, one with narrow-based in-toeing gait, one with broad-based gait with unilateral intoeing). One did not achieve walking ability. 13 patients presented progressive lower limbs hypertonia without overt pyramidal signs. Five patients reported exaggerated startle, three developed upper body (prominently cervical) dystonia in the second decade, with or without bradykinesia (2/13). Treatment efficacy was variable: botulinum toxin was (at least partially) effective in 5/6, levodopa in 1 of 4 treated patients. CTNNB1-syndrome is associated with a peculiar, but recognizable movement disorder phenotype, encompassing complex gait disorders with progressive lower limb hypertonia, exaggerated startle, and possible occurrence in the second decade of life of upper body dystonia with or without bradykinesia.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicola Specchio reports financial support was provided by Italian Ministry of Health. Nicola Specchio reports financial support was provided by Italian Ministry of Education and Merit. Nicola Specchio reports a relationship with BioMarin Pharmaceutical Inc that includes: consulting or advisory and travel reimbursement. Nicola Specchio reports a relationship with Jazz Pharmaceuticals Inc that includes: consulting or advisory and travel reimbursement. Nicola Specchio reports a relationship with UCB that includes: consulting or advisory. Nicola Specchio reports a relationship with Takeda that includes: consulting or advisory. Nicola Specchio reports a relationship with Angeun that includes: consulting or advisory. Nicola Specchio reports a relationship with Zogenix that includes: consulting or advisory. Enrico Bertini reports a relationship with Roche that includes: consulting or advisory. Enrico Bertini reports a relationship with Pfizer that includes: consulting or advisory. Enrico Bertini reports a relationship with Biogen that includes: consulting or advisory and travel reimbursement. Enrico Bertini reports a relationship with PTC that includes: consulting or advisory. Enrico Bertini reports a relationship with Sarepta that includes: consulting or advisory. Enrico Bertini reports a relationship with Italian Ministry of Health that includes: funding grants. Nicola Specchio reports a relationship with Italian Ministry of Health that includes: funding grants. Roberta Onesimo reports a relationship with Biomarin that includes: consulting or advisory and speaking and lecture fees. Roberta Onesimo reports a relationship with Roche that includes: speaking and lecture fees. Roberta Onesimo reports a relationship with QED that includes: funding grants. Roberta Onesimo reports a relationship with Sanofi that includes: funding grants. Giuseppe Zampino reports a relationship with Biomarin that includes: consulting or advisory and travel reimbursement. Giuseppe Zampino reports a relationship with MSD that includes: funding grants. Giuseppe Zampino reports a relationship with Pfizer that includes: funding grants. Giuseppe Zampino reports a relationship with Novo Nordisk that includes: funding grants. Giuseppe Zampino reports a relationship with Gedeon Richter that includes: funding grants. Giuseppe Zampino reports a relationship with Theracon that includes: funding grants. Giuseppe Zampino reports a relationship with Italian Ministry of Health that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.