A 10 years old boy presented with right lower limb dystonia since he was 1 year old. Symptom is better in the morning and worse with activity. He also had bilateral ptosis and waddling gait which are worse when fatigued. Investigations including anti-acetylcholine receptor antibody, metabolic profile, electrophysiological study and magnetic resonance of the brain was negative. Chromosomal microarray showed 16p13.3 duplication, paternally inherited with unknown significance. He was initially started on Levodopa without improvement of dystonia.  Whole exome sequencing showed two heterozygous mutations (c.1669G>A, p. Ala557Thr, maternal, pathogenic; c938_939delT, p.phe313Cysfs*7, likely pathogenic, paternal) in the CHAT gene associated autosomal recessive congenital myasthenia. Patient report significant improvement after starting Pyridostigmine.

We report a case of congenital myasthenia due to CHAT gene mutation, presenting with limb dystonia which responded to pyridostigmine treatment.

CHAT gene, which is located on chromosome 10q11.23, encodes choline acetyltransferase. This enzyme facilitates the synthesis of neurotransmitter acetylcholine. CHAT gene mutation accounts for 4-5% of CMS. CMS presenting with dystonia is extremely rare and has only been reported in a case with COLQ gene mutation. Neuropathologic studies associate dystonia to disease in the basal ganglia. CHAT protein is expressed in the basal ganglia. Disruption of cholinergic regulation of basal ganglia function is a plausible pathogenesis of CHAT mutation associated dystonia. Our case further expands the phenotypic heterogeneity of CMS/CHAT gene mutation.