- Abnormal lower motor neuron morphology (HP:0002366): Any structural anomaly of the lower motor neuron. Evidence: TAS. Onset: Late onset (HP:0003584). (OMIM:614298)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: TAS. (OMIM:614298)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: TAS. (OMIM:614298)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: TAS. (OMIM:614298)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614298)
- Distal amyotrophy (HP:0003693): Muscular atrophy affecting muscles in the distal portions of the extremities. Evidence: TAS. (OMIM:614298)
- Scapular winging (HP:0003691): Abnormal protrusion of the scapula away from the surface of the back. Evidence: TAS. (OMIM:614298)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. (OMIM:614298)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: TAS. (OMIM:614298)
- Neurodegeneration (HP:0002180): Progressive loss of neural cells and tissue. Evidence: PCS. (PMID:21981780)
- Oromandibular dystonia (HP:0012048): A kind of focal dystonia characterized by forceful contractions of the face, jaw, and/or tongue causing difficulty in opening and closing the mouth and often affecting chewing and speech. Evidence: PCS. Frequency: 10/24. (PMID:21981780)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: TAS. (OMIM:614298)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/24. (PMID:21981780)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 2/24. (PMID:21981780)
- Emotional lability (HP:0000712): Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances. Evidence: TAS. (OMIM:614298)
- Motor axonal neuropathy (HP:0007002): Progressive impairment of function of motor axons with muscle weakness, atrophy, and cramps. The deficits are length-dependent, meaning that muscles innervated by the longest nerves are affected first, so that for instance the arms are affected at a later age than the onset of deficits involving the lower leg. Evidence: PCS. Frequency: 8/18. (PMID:21981780)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: PCS. Frequency: 15/23. (PMID:21981780)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: TAS. (OMIM:614298)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. (OMIM:614298)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. (OMIM:614298)
- Eye of the tiger anomaly of globus pallidus (HP:0002454): The presence, on T2-weighted magnetic resonance imaging, of markedly low signal intensity of the globus pallidus that surrounds a central region of high signal intensity in the anteromedial globus pallidus, producing an eye-of-the-tiger appearance. The sign is thought to represent iron accumulation in the globus pallidus. Evidence: PCS. Frequency: 1/24. (PMID:21981780)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 19/24. (PMID:21981780)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: TAS. (OMIM:614298)
- Parkinsonism (HP:0001300): Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait. Evidence: PCS. Frequency: 13/18. (PMID:21981780)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: PCS. Frequency: 14/18. (PMID:21981780)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: TAS. (OMIM:614298)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: TAS. (OMIM:614298)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 17/24. (PMID:21981780)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614298)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: TAS. (OMIM:614298)
- Impulsivity (HP:0100710): Acting on the spur of the moment or on a momentary basis without consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in behavior that is uninhibited, cannot be inhibited, and is uncontrolled. The possibility of repression is inconceivable. Evidence: PCS. (PMID:21981780)
- Lewy bodies (HP:0100315). Evidence: TAS. (OMIM:614298)
- Progressive visual loss (HP:0000529): A reduction of previously attained ability to see. Evidence: TAS. (OMIM:614298)
- Dementia (HP:0000726): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: TAS. (OMIM:614298)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:21981780)
- Abnormal pyramidal sign (HP:0007256): Functional neurological abnormalities related to dysfunction of the pyramidal tract. Evidence: PCS. Frequency: 18/24. (PMID:21981780)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 20/23. (PMID:21981780)
- Loss of ambulation (HP:0002505): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 8/24. Onset: Young adult onset (HP:0011462). (PMID:21981780)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: TAS. (OMIM:614298)
- Autosomal dominant inheritance (HP:0000006): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: IEA. (OMIM:614298)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. (OMIM:614298)
These phenotypes are associated with the disease neurodegeneration with brain iron accumulation 4 (OMIM:614298).