Childhood onset dystonia, chorea or related movement disorder
Gene: SLC18A2
Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence (at least four unrelated cases and functional evidence) available for the association of this gene to movement disorders including dystonia. Hence, this gene can be promoted to green rating at the next GMS review.Created: 10 Aug 2023, 11:23 a.m. | Last Modified: 10 Aug 2023, 11:23 a.m.
Panel Version: 3.36
PMID:23363473 - Eight children from an extended consanguineous Saudi Arabian family had a complex neurological disorder apparent since infancy. This disorder is characterised by abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. They were identified with a homozygous SLC18A2 variant (p.Pro387Leu). Functional evaluation showed that protein harbouring this variant has dramatically reduced activity than wild type protein, suggesting severe, but not complete loss of function as mechanism of action.
PMID:26497564 - Two male siblings from a consanguineous family was reported with a disorder comprising truncal hypotonia, a general paucity of movements, extrapyramidal signs and cognitive delay. They were identified with a homozygous SLC18A2 variant (p.Pro237His).
PMID:31240161 - A child from a consanguineous family presented with hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems and was identified with a homozygous SLC18A2 variant (p.Pro316Ala).
PMID:34078222 - A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was also diagnosed with infantile parkinsonism-dystonia-2 and was identified with the homozygous variant (p.Pro237His) reported in PMID:26497564.
This gene has been associated with relevant phenotypes in OMIM (PMID:618049), but not in Gene2Phenotype.Created: 10 Aug 2023, 10:30 a.m. | Last Modified: 10 Aug 2023, 11:19 a.m.
Panel Version: 3.33
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Parkinsonism-dystonia, infantile, 2, OMIM:618049
Publications
At least three unrelated families reported, potential treatment implications. Associated with intellectual disability and epilepsy as well as prominent movement disorder.Created: 8 Sep 2020, 11:57 p.m. | Last Modified: 8 Sep 2020, 11:57 p.m.
Panel Version: 1.51
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Parkinsonism-dystonia, infantile, 2, MIM# 618049
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: slc18a2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SLC18A2 were changed from Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism); Vesicular monoamine transporter deficiency to ?Parkinsonism-dystonia, infantile, 2, OMIM:618049
Publications for gene: SLC18A2 were set to 27830117; 28477711; 26497564; 23363473; 27520881; 24398404; 24018103; 27604308
Tag Q3_23_promote_green tag was added to gene: SLC18A2.
Source PanelApp was added to SLC18A2. Mode of inheritance for gene SLC18A2 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism); Vesicular monoamine transporter deficiency for gene: SLC18A2 Publications for gene SLC18A2 were changed from to 27830117; 28477711; 26497564; 23363473; 27520881; 24398404; 24018103; 27604308
gene: SLC18A2 was added gene: SLC18A2 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: SLC18A2 was set to