A dystonia characterized by autosomal dominant inheritance of recurrent brief involuntary hyperkinesias triggered by sudden movements that has material basis in variation in the chromosome region 16q13-q22.1.

MECR-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined.

Benign familial infantile seizures-5 (BFIS5) is an autosomal dominant neurologic disorder characterized by onset of afebrile seizures during infancy. In most cases, the seizures remit by age 2 years, although some patients may have single or a few seizures later in childhood. The seizures respond well to treatment with sodium channel blockers, and patients have normal subsequent psychomotor development. Some patients may develop paroxysmal kinesigenic dyskinesia around puberty (summary by Gardella et al., 2016 and Anand et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764).

Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS) is an autosomal recessive complex neurologic disorder characterized by global developmental delay with impaired intellectual development and language delay. In addition, most patients develop a paroxysmal hyperkinetic movement disorder in the first months or years of life manifest as sudden falls or backward propulsion, eye or head deviation, and dystonic limb posturing followed by chorea and dyskinetic movements. The episodes are pharmacoresistant to anticonvulsant medication. EEG may show interictal abnormalities, but are usually not consistent with epilepsy. However, some patients may also develop epileptic seizures or only have seizures without a movement disorder (summary by Doummar et al., 2020).

ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency.

Generalized epilepsy-paroxysmal dyskinesia syndrome is characterised by the association of paroxysmal dyskinesia and generalised epilepsy (usually absence or generalised tonic-clonic seizures) in the same individual or family. The prevalence is unknown. Analysis in one of the reported families led to the identification of a causative mutation in the <i>KCNMA1</i> gene (chromosome 10q22), encoding the alpha subunit of the BK channel. Transmission is autosomal dominant.