Childhood onset dystonia, chorea or related movement disorder

Gene: ADCY5

Green List (high evidence)

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 2:26 p.m. | Last Modified: 11 Mar 2026, 2:26 p.m.

Panel Version: 7.15

Comment on mode of inheritance: There are at least four unrelated families reported with biallelic ADCY5 variants and with childhood-onset movement disorder.

As there is sufficient evidence available for the association of both monoallelic and biallelic ADCY5 variants with the phenotype, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.

Created: 4 Oct 2025, 3:19 p.m. | Last Modified: 4 Oct 2025, 3:19 p.m.

Panel Version: 7.10

Comment on phenotypes: OMIM phenotypes accessed on 04 October 2025.

Created: 4 Oct 2025, 3:16 p.m. | Last Modified: 4 Oct 2025, 3:16 p.m.

Panel Version: 7.9

As previously reported, monoallelic variants in ADCY5 gene are associated with familial dyskinesia with facial myokymia (FDFM), which is an autosomal dominant movement disorder characterised by childhood onset of involuntary choreiform or dystonic movements that involve the limb and facial muscles. There are multiple families reported with this phenotype (MIM #606703).

As reviewed by Cassandra Smith, biallelic variants in ADCY5 gene are now associated with disease phenotypes (MIMs #619647 & #619651).

Autosomal recessive dyskinesia with orofacial involvement (MIM #619647) is characterised by the onset of abnormal involuntary movements, mainly affecting the limbs and causing walking difficulties, in the first decade. Eight patients from two different families were reported with this phenotype. They were identified with either compound heterozygous (p.Gly137Cysfs*184 & p.Arg1013Cys) or homozygous variants (p.Asp588Asn) in ADCY5 gene.

Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (MIM #619651) is an autosomal recessive complex neurological disorder characterised by severe global developmental delay with axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements, including dystonia, myoclonus, spasticity, and orofacial dyskinesia. It is the most severe manifestation of ADCY5-related dyskinetic disorders. There are five patients from two different families reported with this phenotype and they were identified with homozygous variants (p.Arg1238Trp & c.897+1G>T).

Created: 4 Oct 2025, 3:12 p.m. | Last Modified: 4 Oct 2025, 3:15 p.m.

Panel Version: 7.7

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dyskinesia with orofacial involvement, autosomal dominant, OMIM:606703; dyskinesia with orofacial involvement, autosomal dominant, MONDO:0800028; Dyskinesia with orofacial involvement, autosomal recessive, OMIM:619647; dyskinesia with orofacial involvement, autosomal recessive, MONDO:0030625; Neurodevelopmental disorder with hyperkinetic movements and dyskinesia, OMIM:619651; neurodevelopmental disorder with hyperkinetic movements and dyskinesia, MONDO:0859211

Publications

• 28971144
• 30975617
• 33704598
• 34631954

Green List (high evidence)

Multiple families reported with biallelic, likely LOF variants associated with a severe phenotype

Extends the potential MOI

Created: 10 Aug 2025, 10:24 a.m. | Last Modified: 10 Aug 2025, 10:24 a.m.

Panel Version: 7.3

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 28971144
• 30975617
• 34631954
• 33704598

Green List (high evidence)