- Abnormal lower motor neuron morphology (HP:0002366): Any structural anomaly of the lower motor neuron. Evidence: TAS. (OMIM:606070)
- 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: 7/11. (PMID:9837826)
- Hand muscle weakness (HP:0030237): Reduced strength of the musculature of the hand. Evidence: PCS. Frequency: 20/24. (PMID:19344878)
- Middle age onset (HP:0003596): A type of adult onset with onset of symptoms at the age of 40 to 60 years. Evidence: PCS. Frequency: 10/12. (PMID:9837826)
- Bulbar signs (HP:0002483). Evidence: TAS. (OMIM:606070)
- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: PCS. Frequency: 12/12. (PMID:9837826)
- Hoarse voice (HP:0001609): Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky. Evidence: IEA. (OMIM:606070)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 2/12. (PMID:9837826)
- Distal sensory impairment (HP:0002936): An abnormal reduction in sensation in the distal portions of the extremities. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:606070)
- Rimmed vacuoles (HP:0003805): Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions. Evidence: PCS. Frequency: 5/6. (PMID:9837826)
- Aspiration (HP:0002835): Inspiration of a foreign object into the airway. Evidence: IEA. (OMIM:606070)
- Bowing of the vocal cords (HP:0008756): Bowing (abnormal curvature) of the vocal folds. Evidence: IEA. (OMIM:606070)
- Shoulder girdle muscle weakness (HP:0003547): The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders. Evidence: PCS. Frequency: 12/36. (PMID:19344878;PMID:9837826)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: TAS. (OMIM:606070)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 13/19. (PMID:19344878)
- Centrally nucleated skeletal muscle fibers (HP:0003687): An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells). Evidence: PCS. Frequency: 3/6. (PMID:9837826)
- Bulbar palsy (HP:0001283): Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia. Evidence: TAS. (OMIM:606070)
- 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: TAS. (OMIM:606070)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: PCS. Frequency: 34/34. (OMIM:606070;PMID:19344878)
- Distal lower limb muscle weakness (HP:0009053): Reduced strength of the distal musculature of the legs. Evidence: PCS. Frequency: 23/24. (PMID:19344878)
- 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. Frequency: Occasional (HP:0040283). (OMIM:606070)
- Amyotrophic lateral sclerosis (HP:0007354). Evidence: TAS. (OMIM:606070)
- Respiratory insufficiency due to muscle weakness (HP:0002747). Evidence: TAS. (OMIM:606070)
- Decreased nerve conduction velocity (HP:0000762): A reduction in the speed at which electrical signals propagate along the axon of a neuron. Evidence: PCS. Frequency: 3/7. (PMID:9837826)
- 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: PCS. (PMID:19344878)
- Abnormal upper motor neuron morphology (HP:0002127): Any structural anomaly that affects the upper motor neuron. Evidence: TAS. (OMIM:606070)
- Increased variability in muscle fiber diameter (HP:0003557): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: PCS. Frequency: 1/1. (PMID:19344878)
These phenotypes are associated with the disease amyotrophic lateral sclerosis type 21 (OMIM:606070).