A number sign (#) is used with this entry because of evidence that autosomal recessive dyskinesia with orofacial involvement (DSKOR) is caused by homozygous or compound heterozygous mutation in the ADCY5 gene (600293) on chromosome 3q21.

Heterozygous mutation in the ADCY5 gene can cause a similar autosomal dominant movement disorder (DSKOD; 606703), and biallelic ADCY5 mutation can cause a more severe complex neurologic disorder (NEDHYD; 619651).

Autosomal recessive dyskinesia with orofacial involvement (DSKOR) is characterized by the onset of abnormal involuntary movements, mainly affecting the limbs and causing walking difficulties, in the first decade. The severity is variable; some patients have orofacial dyskinesia resulting in speech difficulties, or develop neuropsychiatric features, including anxiety and social withdrawal. Cardiomyopathy has rarely been described and may be a manifestation of the disorder (summary by Bohlega et al., 2019).

Barrett et al. (2017) reported 2 sibs with generalized dystonia and superimposed myoclonus. The proband was a 27-year-old woman who had mildly delayed walking at 18 months of age as well as speech delay, and developed involuntary movements diagnosed as dystonia at age 3 years. She had frequent falls due to involuntary myoclonic movements. Movements lessened with sleep and did not improve with alcohol or caffeine. Her 24-year-old brother had speech delay and developed cramping in the hands and neck at age 8 years. His gait worsened at 15 years of age secondary to worsening lower extremity dystonia following a growth spurt. The disorder was slowly progressive; neuropsychiatric symptoms were not reported. Brain imaging was normal in both patients. Neither parent had a movement disorder.

Bohlega et al. (2019) reported 6 sibs, ranging from 6 to 20 years of age and born of consanguineous Arab parents, with onset of a hyperkinetic movement disorder in the first decade (range 2 to 10 years). Most patients had gross motor and/or speech delay and poor overall growth. Features included axial hypotonia, awkward gait with frequent falls, facial grimacing, oromandibular dystonia with abnormal twisting movements of the lips, cheeks, and tongue, dysarthria, dystonic posturing, axial myoclonus, torticollis, and intermittent limb spasms, flailing, or muscle jerks. Some had lordosis or scoliosis; none had myokymia. One patient had dilated cardiomyopathy with decreased ejection fraction and 2 had hypothyroidism. The 4 older sibs had social phobia and anxiety and were withdrawn, although cognitive function was intact. Brain imaging was normal. The parents were clinically unaffected.

The transmission pattern of DSKOR in the family reported by Barrett et al. (2017) was consistent with autosomal recessive inheritance.

In 2 sibs with DSKOR, Barrett et al. (2017) identified compound heterozygous mutations in the ADCY5 gene (600293.0007 and 600293.0008). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed. The parents, who were each a heterozygous carrier of 1 of the mutations, were clinically unaffected.

In 6 sibs, born of consanguineous Arab parents, with DSKOR, Bohlega et al. (2019) identified a homozygous missense mutation in the ADCY5 gene, (D588N; 600293.0009). The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The parents, who were heterozygous carriers of the mutation, were clinically unaffected.