B.02 Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy

Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.

Long-Term Efficacy of Botulinum A Toxin for Blepharospasm and Hemifacial Spasm

Objective:To determine whether the duration of relief from symptoms in patients with essential blepharospasm (EB) or hemifacial spasm (HFS) who receive serial treatments with botulinum toxin type A (BtA) changes over the long-term.Methods:Retrospective longitudinal comparative analysis. The main outcome measure is the mean duration of relief from symptoms after an injection with BtA. Participants included 34 patients who received 30 or more serial BtA treatments for facial dyskinesia (EB or HFS). Repeated measures and linear regression analyses were used to determine trends and the mean duration of relief from symptoms was compared between early (first ten effective treatments) and late (last ten treatments) sessions in each group.Results:In the EB group (18 patients), the mean duration of relief was 13.5 weeks for the early and 11.4 weeks for the late sessions (P=0.04). In the HFS group (16 patients) the mean duration of relief was 12.4 weeks in both treatment periods (P=0.91). The duration of relief had a small negative correlation with mean late session BtA dose in the EB group (P=0.03) but no correlation in the HFS group (P=0.12).Conclusions:There was a trend towards a decreased duration of relief from symptoms in patients with EB over the long-term, but no changes for HFS. The treatment remains effective in relieving symptoms and signs for both conditions.