- Language impairment (HP:0002463): Language impairment is a deficit in comprehension or production of language that includes reduced vocabulary, limited sentence structure, or impairments in written or spoken communication. Language abilities are substantially and quantifiably below age expectations. Evidence: PCS. Frequency: 3/3. (PMID:4045952;PMID:11050011;PMID:34354969)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: PCS. Frequency: 3/3. (PMID:22398176;PMID:4045952)
- Hypochromic microcytic anemia (HP:0004840): A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes. Evidence: PCS. Frequency: 4/4. (PMID:4045952;PMID:11050011)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 3/3. (PMID:11050011;PMID:34354969)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: PCS. Frequency: 1/1. (PMID:34354969)
- 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: 3/3. (PMID:26242992;PMID:34354969)
- 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: PCS. Frequency: 3/3. (PMID:11118249;PMID:34354969)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/4. (PMID:4045952)
- Abnormal basal ganglia MRI signal intensity (HP:0012751): A deviation from normal signal on magnetic resonance imaging (MRI) of the basal ganglia. Evidence: PCS. Frequency: 1/1. (PMID:34354969)
- 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: PCS. Frequency: 1/1. (PMID:26242992)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 9/9. (PMID:11118249;PMID:26242992;PMID:11050011;PMID:34354969)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/6. (PMID:22398176;PMID:4045952;PMID:34354969)
- Autism (HP:0000717): Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. Autism begins in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). Evidence: PCS. Frequency: 1/1. (PMID:34354969)
- Sideroblastic anemia (HP:0001924): Sideroblastic anemia results from a defect in the incorporation of iron into the heme molecule. A sideroblast is an erythroblast that has stainable deposits of iron in cytoplasm (this can be demonstrated by Prussian blue staining). Evidence: PCS. Frequency: 3/3. (PMID:4045952;PMID:11050011)
- Pappenheimer bodies (HP:0020081): A type of erythrocyte inclusion characterized by basophilic stippling of erythrocytes, that is, by numerous very small coarse or fine blue granules within the cytoplasm with the additional stipulation that the stippled particles are due to iron granules (demonstrable by the Prussian blue stain). Evidence: PCS. Frequency: 3/3. (PMID:11118249;PMID:22398176)
- Interictal EEG abnormality (HP:0025373): Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge. Evidence: PCS. Frequency: 1/1. (PMID:34354969)
- 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: 3/3. (PMID:4045952)
- 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: 15/15. (PMID:11118249;PMID:22398176;PMID:26242992;PMID:4045952;PMID:11050011;PMID:34354969)
- 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: 15/15. (PMID:11118249;PMID:26242992;PMID:4045952;PMID:11050011;PMID:34354969)
- Nonprogressive cerebellar ataxia (HP:0002470). Evidence: PCS. Frequency: 11/11. (PMID:26242992;PMID:4045952;PMID:11050011)
- Dysdiadochokinesis (HP:0002075): A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible. Evidence: PCS. Frequency: 4/4. (PMID:11118249;PMID:4045952;PMID:11050011)
- Abnormality of movement (HP:0100022): An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements. Evidence: PCS. Frequency: 1/1. (PMID:11118249)
- Increased erythrocyte protoporphyrin concentration (HP:0012187): Concentration of protoporphyrins in erythrocytes above the upper limit of normal. Evidence: PCS. Frequency: 8/8. (PMID:11118249;PMID:22398176;PMID:4045952;PMID:11050011)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: PCS. Frequency: 2/2. (PMID:26242992)
- 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: 1/1. (PMID:11118249)
- X-linked recessive inheritance (HP:0001419): A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. Evidence: PCS. (PMID:10196363)
- Ophthalmoplegia (HP:0000602): Paralysis of one or more extraocular muscles that are responsible for eye movements. Evidence: PCS. Frequency: 5/5. (PMID:26242992)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: PCS. Frequency: 1/1. (PMID:26242992)
- Poikilocytosis (HP:0004447): The presence of abnormally shaped erythrocytes. Evidence: PCS. Frequency: 3/3. (PMID:22398176;PMID:4045952)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 2/2. (PMID:4045952)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 3/6. (PMID:4045952;PMID:11050011)
- Dysmetria (HP:0001310): A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements. Evidence: PCS. Frequency: 3/3. (PMID:4045952)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: PCS. Frequency: 1/1. (PMID:11050011)
- Organic aciduria (HP:0001992): Excretion of non-amino organic acids in urine. Evidence: PCS. Frequency: 1/1. (PMID:34354969)
- 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:11118249)
- Abnormal brainstem morphology (HP:0002363): An anomaly of the brainstem. Evidence: PCS. Frequency: 2/2. (PMID:11118249)
- Intention tremor (HP:0002080): A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). Evidence: PCS. Frequency: 1/1. (PMID:4045952)
- Erythroid hyperplasia (HP:0012132): Increased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow. Evidence: PCS. Frequency: 1/1. (PMID:4045952)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: PCS. Frequency: 1/1. (PMID:11050011)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 5/5. (PMID:11118249;PMID:4045952;PMID:34354969)
- Weight loss (HP:0001824): Reduction of total body weight. Evidence: PCS. Frequency: 2/2. (PMID:11050011;PMID:34354969)
- Abducens palsy (HP:0006897): Malfunction of the abducens nerve as manifested by impairment of the ability of the affected eye to be moved outward. Patients who develop abducens nerve palsy often present with binocular horizontal diplopia, which is a double vision when looking at objects side by side. There will be a notable weakness of the ipsilateral lateral rectus muscle leading to a deficit in of eye abduction on the affected side. Some patients may present with a constant head turning movement to maintain binocular fusion and to lessen the degree of diplopia. Evidence: PCS. Frequency: 1/1. (PMID:11118249)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 3/3. (PMID:11118249;PMID:4045952)
- Target cells (HP:0034280): Target cells (codocytes) have a centrally located disk of hemoglobin surrounded by an area of pallor with an outer rim of hemoglobin adjacent to the cell membrane giving the cell the appearance of a target. Evidence: PCS. Frequency: 1/1. (PMID:11118249)
- Basal ganglia gliosis (HP:0006999): Focal proliferation of glial cells in the basal ganglia. Evidence: PCS. Frequency: 1/1. (PMID:34354969)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 7/7. (PMID:26242992;PMID:11050011)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 7/7. (PMID:11118249;PMID:22398176;PMID:4045952;PMID:34354969)
- Postural instability (HP:0002172): A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps. Evidence: PCS. Frequency: 9/9. (PMID:11118249;PMID:22398176;PMID:26242992;PMID:34354969)
- Anisocytosis (HP:0011273): Abnormally increased variability in the size of erythrocytes. Evidence: PCS. Frequency: 3/3. (PMID:11118249;PMID:22398176;PMID:4045952)
- Schizophrenia (HP:0100753): A mental disorder characterized by a disintegration of thought processes and emotional responsiveness. It most commonly manifests as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking. It is accompanied by significant social or occupational dysfunction. The onset of symptoms typically occurs in young adulthood, with a global lifetime prevalence of about 1%. This term is not a helpful parent term to describe abnormal experiences. Evidence: PCS. Frequency: 1/1. (PMID:11118249)
- Bone marrow hypercellularity (HP:0031020): A larger than normal amount or percentage of hematopoietic cells relative to marrow fat. Evidence: PCS. Frequency: 2/2. (PMID:4045952)
- Howell-Jolly bodies (HP:0032550): Howell-Jolly bodies are small, intra-erythrocytic remnants of erythrocyte nuclei. These inclusions are solitary in each erythrocyte and strongly basophilic. These are often confused with overlying platelets, but can be distinguished by the presence of a halo around overlying platelets. Evidence: PCS. Frequency: 1/1. (PMID:11118249)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 3/3. (PMID:4045952;PMID:11050011;PMID:34354969)
- Positive Romberg sign (HP:0002403): The patient stands with the feet placed together and balance and is asked to close his or her eyes. A loss of balance upon eye closure is a positive Romberg sign and is interpreted as indicating a deficit in proprioception. Evidence: PCS. Frequency: 1/1. (PMID:4045952)
- Diminished deep tendon reflex (HP:0001315): A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon. Evidence: PCS. Frequency: 3/3. (PMID:11050011;PMID:34354969)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 1/1. (PMID:34354969)
These phenotypes are associated with the disease X-linked sideroblastic anemia with ataxia (OMIM:301310).