Pantothenate kinase-associated neurodegeneration (PKAN) is a type of neurodegeneration with brain iron accumulation (NBIA). The phenotypic spectrum of PKAN includes classic PKAN and atypical PKAN. Classic PKAN is characterized by early-childhood onset of progressive dystonia, dysarthria, rigidity, and choreoathetosis. Pigmentary retinal degeneration is common. Atypical PKAN is characterized by later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease.

Aceruloplasminemia is characterized by iron accumulation in the brain and viscera. The clinical triad of retinal degeneration, diabetes mellitus (DM), and neurologic disease is seen in individuals ranging from age 30 years to older than 70 years. The neurologic findings of movement disorder (blepharospasm, grimacing, facial and neck dystonia, tremors, chorea) and ataxia (gait ataxia, dysarthria) correspond to regions of iron deposition in the brain. Individuals with aceruloplasminemia often present with anemia prior to onset of DM or obvious neurologic problems. Cognitive dysfunction including apathy and forgetfulness occurs in more than half of individuals with this condition.

Aromatic L-amino acid decarboxylase deficiency (AADCD) is an autosomal recessive inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency (Abeling et al., 2000). The disorder is clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction, usually beginning in infancy or childhood (summary by Brun et al., 2010).

Familial adult myoclonic epilepsy-2 (FAME2) is an autosomal dominant neurologic disorder characterized by onset of tremor affecting the fingers, hand, and voice in adolescence or young adulthood with somewhat later onset of rhythmic myoclonic jerks and generalized tonic-clonic seizures. Electrophysiologic studies are consistent with cortical reflex myoclonus. Some patients may show cognitive decline or migraines; photosensitivity is common (summary by De Fusco et al., 2014; Crompton et al., 2012). For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068).

DYT13 type primary dystonia has characteristics of focal or segmental dystonia with cranial, cervical, or upper limb involvement. It has been reported in individuals from three generations of one large Italian family. Age of onset varied between 5 years and adulthood. The clinical manifestations were generally mild and slowly progressive. The causative gene locus has been identified on chromosome 1p36.13-1p36.32. Transmitted in an autosomal dominant manner.

DYT1 early-onset isolated dystonia typically presents in childhood or adolescence and only on occasion in adulthood. Dystonic muscle contractions causing posturing or irregular tremor of a leg or arm are the most common presenting findings. Dystonia is usually first apparent with specific actions such as writing or walking. Over time, the contractions frequently (but not invariably) become evident with less specific actions and spread to other body regions. No other neurologic abnormalities are present. Disease severity varies considerably even within the same family. Isolated writer's cramp may be the only sign.

Parkinson's disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.\n\nOften the first symptom of Parkinson's disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson's disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.\n\nParkinson's disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson's disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.\n\nGenerally, Parkinson's disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson's disease.

Neuroferritinopathy is an adult-onset progressive movement disorder characterized by chorea or dystonia and speech and swallowing deficits. The movement disorder typically affects one or two limbs and progresses to become more generalized within 20 years of disease onset. When present, asymmetry in the movement abnormalities remains throughout the course of the disorder. Most individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time.

Torsion dystonia-2 (DYT2) is an autosomal recessive neurologic disorder characterized by onset of symptoms in childhood or adolescence. 'Dystonia' is characterized by involuntary, sustained muscle contractions affecting 1 or more sites of the body; 'torsion' refers to the twisting nature of body movements observed in dystonia. DYT2 first affects distal limbs and later involves the neck, orofacial, and craniocervical regions. DYT2 is slowly progressive but mild overall (summary by Muller and Kupke, 1990; Nemeth, 2002; Khan et al., 2003).

Idiopathic torsion dystonia (ITD) is a clinically and genetically heterogeneous group of movement disorders characterized by sustained dystonic muscle contractions causing involuntary twisting movements and/or postures, where causes such as cerebral lesions (especially of the basal ganglia), drugs, or other neurologic disorders have not been found. Adult-onset torsion dystonia usually remains focal and is localized in the upper part of the body (summary by Leube et al., 1996).

Dystonia-21 (DYT21) is an autosomal dominant form of pure torsion dystonia, a movement disorder characterized by sustained muscle contractions causing twisting and repetitive movements and abnormal postures (summary by Norgren et al., 2011).

Dystonia-24 is an autosomal dominant form of focal dystonia affecting the neck, laryngeal muscles, and muscles of the upper limbs (summary by Charlesworth et al., 2012).

Myoclonic dystonia-26 (DYT26) is an autosomal dominant neurologic disorder characterized by onset of myoclonic jerks affecting the upper limbs in the first or second decade of life. The disorder is progressive, and patients later develop dystonia with predominant involvement of the craniocervical regions and sometimes the trunk and/or lower limbs. Dystonia dominates the clinical picture (summary by Mencacci et al., 2015).

Developmental and epileptic encephalopathy-29 (DEE29) is an autosomal recessive neurologic disorder characterized by the onset of refractory myoclonic seizures in the first months of life. Affected individuals have poor overall growth, congenital microcephaly with cerebral atrophy and impaired myelination on brain imaging, spasticity with abnormal movements, peripheral neuropathy, and poor visual fixation (summary by Simons et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.

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.