- Muscle fiber splitting (HP:0003555, a Human Phenotype Ontology term): Fiber splitting or branching is a common finding in human and rat skeletal muscle pathology. Fiber splitting refers to longitudinal halving of the complete fiber, while branching originates from a regenerating end of a necrotic fiber as invaginations of the sarcolemma. In fiber branching, one end of the fiber remains intact as a single entity, while the other end has several branches. Evidence: PCS. (PMID:27040688)
- Elevated circulating creatine kinase activity (HP:0003236, a Human Phenotype Ontology term): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 3/4. (PMID:27040688)
- Progressive (HP:0003676, a Human Phenotype Ontology term): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: TAS. (OMIM:616924)
- Pyloric stenosis (HP:0002021, a Human Phenotype Ontology term): Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss. Evidence: PCS. (PMID:27040688)
- Myopathy (HP:0003198, a Human Phenotype Ontology term): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. (PMID:27040688)
- Somatic sensory dysfunction (HP:0003474, a Human Phenotype Ontology term): An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing. Evidence: PCS. (PMID:27040688)
- Sensory axonal neuropathy (HP:0003390, a Human Phenotype Ontology term): An axonal neuropathy of peripheral sensory nerves. Evidence: PCS. (PMID:27040688)
- Sensorimotor neuropathy (HP:0007141, a Human Phenotype Ontology term). Evidence: IEA. (OMIM:616924)
- Lower limb muscle weakness (HP:0007340, a Human Phenotype Ontology term): Weakness of the muscles of the legs. Evidence: PCS. Frequency: 4/4. (PMID:27040688)
- Variable expressivity (HP:0003828, a Human Phenotype Ontology term): A variable severity of phenotypic features. Evidence: TAS. (OMIM:616924)
- Rimmed vacuoles (HP:0003805, a Human Phenotype Ontology term): 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. (PMID:27040688)
- Distal sensory impairment (HP:0002936, a Human Phenotype Ontology term): An abnormal reduction in sensation in the distal portions of the extremities. Evidence: TAS. (OMIM:616924)
- Waddling gait (HP:0002515, a Human Phenotype Ontology term): 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: PCS. (PMID:27040688)
- Proximal muscle weakness (HP:0003701, a Human Phenotype Ontology term): A lack of strength of the proximal muscles. Evidence: TAS. Frequency: Occasional (HP:0040283, a Human Phenotype Ontology term). (OMIM:616924)
- Frequent falls (HP:0002359, a Human Phenotype Ontology term). Evidence: TAS. (OMIM:616924)
- Upper limb amyotrophy (HP:0009129, a Human Phenotype Ontology term): Muscular atrophy involving the muscles of the upper limbs. Evidence: PCS. Frequency: 3/4. (PMID:27040688)
- Hyporeflexia (HP:0001265, a Human Phenotype Ontology term): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. (OMIM:616924)
- EMG: neuropathic changes (HP:0003445, a Human Phenotype Ontology term): The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials). Evidence: PCS. Frequency: 4/4. (PMID:27040688)
- Ragged-red muscle fibers (HP:0003200, a Human Phenotype Ontology term): An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm. Evidence: PCS. (PMID:27040688)
- Babinski sign (HP:0003487, a Human Phenotype Ontology term): 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: 4/4. (PMID:27040688)
- Pes cavus (HP:0001761, a Human Phenotype Ontology term): 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: TAS. (OMIM:616924)
- Upper limb muscle weakness (HP:0003484, a Human Phenotype Ontology term): Weakness of the muscles of the arms. Evidence: PCS. Frequency: 3/4. (PMID:27040688)
- Impaired vibratory sensation (HP:0002495, a Human Phenotype Ontology term): 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: 2/4. (PMID:27040688)
- Lower limb amyotrophy (HP:0007210, a Human Phenotype Ontology term): Muscular atrophy affecting the lower limb. Evidence: PCS. Frequency: 4/4. (PMID:27040688)
- Autosomal dominant inheritance (HP:0000006, a Human Phenotype Ontology term): 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:27040688)
- Increased variability in muscle fiber diameter (HP:0003557, a Human Phenotype Ontology term): An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy. Evidence: PCS. (PMID:27040688)
These phenotypes are associated with the disease Charcot-Marie-Tooth disease axonal type 2CC (OMIM:616924, an entry in Online Mendelian Inheritance in Man).