Phenotypes associated with the disease hypermanganesemia with dystonia 2 (OMIM:617013):
- Progressive neurologic deterioration (HP:0002344). Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Impaired mastication (HP:0005216): An abnormal reduction in the ability to masticate (chew), i.e., in the ability to crush and ground food in preparation for swallowing. Evidence: PCS. Frequency: 1/1. (PMID:29498153)
- Achilles tendon contracture (HP:0001771): A contracture of the Achilles tendon. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- 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: PCS. (PMID:27231142)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: PCS. Frequency: 1/1. (PMID:29498153)
- Bradykinesia (HP:0002067): Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement). Evidence: PCS. Frequency: 2/9. (PMID:27231142)
- 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: PCS. Frequency: 10/10. (PMID:27231142;PMID:29498153)
- 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: PCS. Frequency: 3/10. (PMID:27231142)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. Frequency: 1/1. (PMID:29498153)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/1. (PMID:29498153)
- Scissor gait (HP:0012407): A type of spastic paraparetic gait in which the muscle tone in the adductors is marked. It is characterized by hypertonia and flexion in the legs, hips and pelvis accompanied by extreme adduction leading to the knees and thighs hitting, or sometimes even crossing, in a scissors-like movement. The opposing muscles (abductors) become comparatively weak from lack of use. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- 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: 3/9. (PMID:27231142)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- Hypomimic face (HP:0000338): A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Lower limb hypertonia (HP:0006895). Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: PCS. Frequency: 6/9. (PMID:27231142)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 4/18. (PMID:27231142)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 2/9. (PMID:27231142)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Clumsiness (HP:0002312): Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 3/10. (PMID:27231142)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- 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. (PMID:27231142)
- Hypokinesia (HP:0002375): Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/9. (PMID:27231142)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/10. (PMID:27231142)
- 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: 1/9. (PMID:27231142)
- Limb joint contracture (HP:0003121): A contracture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- Limb dystonia (HP:0002451): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- 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: PCS. Frequency: 2/10. (PMID:27231142;PMID:29498153)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- Ankle clonus (HP:0011448): Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward. Evidence: PCS. Frequency: 3/9. (PMID:27231142)
- Hypermanganesemia (HP:0032097): The concentration of manganese cation in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 3/10. (PMID:27231142;PMID:29498153)
- Hyperintensity of cerebral white matter on MRI (HP:0030890): A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter. Evidence: PCS. Frequency: 10/10. (PMID:27231142)
- 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:27231142)
- Tip-toe gait (HP:0030051): An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait. Evidence: PCS. Frequency: 4/9. (PMID:27231142)
- 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: PCS. Frequency: 3/10. (PMID:27231142;PMID:29498153)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: PCS. Frequency: 1/9. (PMID:27231142)