- 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:20593214)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614409)
- Impaired vibration sensation in the lower limbs (HP:0002166): A decrease in the ability to perceive vibration in the legs. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614409)
- 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: 2/2. (PMID:20593214)
- Urinary incontinence (HP:0000020): Loss of the ability to control the urinary bladder leading to involuntary urination. Evidence: TAS. (OMIM:614409)
- Spastic gait (HP:0002064): Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg. Evidence: TAS. (OMIM:614409)
- Lower limb spasticity (HP:0002061): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: PCS. Frequency: 5/5. (PMID:20593214)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: TAS. (OMIM:614409)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: PCS. Frequency: 4/5. Onset: Congenital onset (HP:0003577). (PMID:20593214)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. (OMIM:614409)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/5. (PMID:20593214)
- Lower limb muscle weakness (HP:0007340): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 5/5. (PMID:20593214)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: TAS. (OMIM:614409)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:614409)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 5/5. (PMID:20593214)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 2/2. (PMID:20593214)
- Hand tremor (HP:0002378): An unintentional, oscillating to-and-fro muscle movement affecting the hand. Evidence: PCS. Frequency: 1/5. (PMID:20593214)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 2/5. (PMID:20593214)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 2/5. (PMID:20593214)
- 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: 5/5. (PMID:20593214)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 2/2. (PMID:20593214)
- Orofacial dyskinesia (HP:0002310). Evidence: PCS. Frequency: 1/5. (PMID:20593214)
- 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: PCS. Frequency: 4/5. (PMID:20593214)
- 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: 3/5. (PMID:20593214)
- Impaired vibratory sensation (HP:0002495): A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient. Evidence: PCS. Frequency: 1/5. (PMID:20593214)
- Knee clonus (HP:0011449): Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Knee clonus can be tested by rapidly pushing the patella towards the toes. Evidence: TAS. (OMIM:614409)
- 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: TAS. (OMIM:614409)
- 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: PCS. Frequency: 5/5. (PMID:20593214)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614409)
- Infertility (HP:0000789). Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614409)
- Jerky ocular pursuit movements (HP:0008003). Evidence: TAS. (OMIM:614409)
- 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:20593214)
- Limb dysmetria (HP:0002406): A type of dysmetria involving the limbs. Evidence: TAS. (OMIM:614409)
- Upper limb dysmetria (HP:0020036): A lack of coordination of arm movement manifested by undershoot or overshoot of the intended position of the arm. Evidence: IEA. (OMIM:614409)
- Spastic paraplegia (HP:0001258): Complete loss of the ability to move the lower limbs accompanied by spasticity of the lower limbs. Evidence: PCS. Frequency: 5/5. (PMID:20593214)
- Head tremor (HP:0002346): An unintentional, oscillating to-and-fro muscle movement affecting head movement. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614409)
- Upper limb spasticity (HP:0006986). Evidence: PCS. Frequency: 5/5. (PMID:20593214)
These phenotypes are associated with the disease hereditary spastic paraplegia 46 (OMIM:614409).