- Distal muscle weakness (HP:0002460): Reduced strength of the musculature of the distal extremities. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- Waddling gait (HP:0002515): Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- 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. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- Hyperlordosis (HP:0003307): Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- Ubiquitin-positive cerebral inclusion bodies (HP:0012083): Nuclear or cytoplasmic aggregates that show positive staining with antibodies against ubiquitin within cells of the brain. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:52430)
- Abnormality of the vertebral column (HP:0000925): Any abnormality of the vertebral column. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- Frontotemporal dementia (HP:0002145): A dementia associated with degeneration of the frontotemporal lobe and clinically associated with personality and behavioral changes such as disinhibition, apathy, and lack of insight. The hallmark feature of frontotemporal dementia is the presentation with focal syndromes such as progressive language dysfunction, or aphasia, or behavioral changes characteristic of frontal lobe disorders. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- Osteolysis (HP:0002797): Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- Elevated circulating alkaline phosphatase concentration (HP:0003155): Abnormally increased serum levels of alkaline phosphatase activity. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- Hip pain (HP:0030838): An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the hip. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:52430)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- 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). (ORPHA:52430)
- Cranial nerve compression (HP:0001293). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Cardiomyopathy (HP:0001638): A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Mutism (HP:0002300): Complete lack of speech or verbal communication in a person despite attempts to engage in conversation. Mutism as a phenomena assumes the individual has previous capacity for speech and in the pediatric population it assumes that the person is past the age of typical language development. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Fasciculations (HP:0002380): Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Aphasia (HP:0002381): An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Dyscalculia (HP:0002442): A specific learning disability involving mathematics and arithmetic. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Abnormal motor neuron morphology (HP:0002450): Any structural anomaly that affects the motor neuron. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Upper motor neuron dysfunction (HP:0002493): A functional anomaly of the upper motor neuron. The upper motor neurons are neurons of the primary motor cortex which project to the brainstem and spinal chord via the corticonuclear, corticobulbar and corticospinal (pyramidal) tracts. They are involved in control of voluntary movements. Dysfunction leads to weakness, impairment of fine motor movements, spasticity, hyperreflexia and abnormal pyramidal signs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Increased susceptibility to fractures (HP:0002659): An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Abnormal calvaria morphology (HP:0002683): Abnormality of the morphology (structure) of the calvaria (skullcap), that is, of that part of the skull that is made up of the superior portions of the frontal bone, occipital bone, and parietal bones and covers the cranial cavity that contains the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Urinary bladder sphincter dysfunction (HP:0002839): Abnormal function of a sphincter of the urinary bladder. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Sensory axonal neuropathy (HP:0003390): An axonal neuropathy of peripheral sensory nerves. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- EMG: chronic denervation signs (HP:0003444): Evidence of chronic denervation on electromyography. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- EMG: neuropathic changes (HP:0003445): The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Weakness of muscles of respiration (HP:0004347): Reduced function of the muscles required to generate subatmospheric pressure in the thoracic cavity during breathing: the diaphragm, the external intercostal and the interchondral part of the internal intercostal muscles. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Calvarial hyperostosis (HP:0004490): Excessive growth of the calvaria. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Amyotrophic lateral sclerosis (HP:0007354). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Abnormal long bone morphology (HP:0011314): An abnormality of size or shape of the long bones. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Fatty replacement of skeletal muscle (HP:0012548): Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:52430)
- Pathologic fracture (HP:0002756): A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:52430)
These phenotypes are associated with the disease Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (ORPHA:52430).