Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings.
These studies establish a role for THAP1 transcriptional regulation at the inception of myelination and implicate abnormal timing of myelination in the pathogenesis of childhood-onset dystonia.
Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission.
Dopa-responsive dystonia (DRD) is a rare inherited disorder characterized by childhood-onset dystonia with diurnal fluctuation and dramatic response to levodopa.
All the subjects except for one family had typical manifestations of autosomal dominant GTPCH-I deficient DRD including early childhood onset dystonia predominantly in the legs, marked diurnal variation, intact cognition, no other systemic symptoms, and excellent sustained response to levodopa.
Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by childhood-onset dystonia and a dramatic response to relatively low doses of levodopa.
Dopa responsive dystonia (DRD) is a disorder characterised by childhood onset dystonia but a wide range of clinical presentations has now been described.
It is also clear that notwithstanding the discovery of GCH1 and hTH mutations responsible for DRD, there remain many important unresolved issues regarding this disorder, including questions of female predominance, phenotypic heterogeneity, and presence of childhood-onset dystonia versus the expected parkinsonism resulting from a striatal DA deficit.
Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings.
We identified the first and homozygous mutation (p.Gly114Ala) in the Mediator subunit 20 gene (MED20) in siblings presenting with infantile-onset spasticity and childhood-onset dystonia, progressive basal ganglia degeneration, and brain atrophy.