Phenotypes associated with the disease nemaline myopathy 2 (OMIM:256030):
- Muscle fiber splitting (HP:0003555): 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. Frequency: 1/7. (PMID:17525139)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: IEA. (OMIM:256030)
- Mitochondrial depletion (HP:0030059): An abnormal reduction in mitochondrial DNA content of cells. Evidence: IEA. (OMIM:256030)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: IEA. (OMIM:256030)
- Narrow mouth (HP:0000160): Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective). Evidence: PCS. Frequency: 3/7. (PMID:17525139)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: IEA. (OMIM:256030)
- Fatty replacement of skeletal muscle (HP:0012548): Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers. Evidence: PCS. Frequency: 3/7. (PMID:17525139)
- Thenar muscle atrophy (HP:0003393): Wasting of thenar muscles, which are located on palm of the hand at the base of the thumb. Evidence: PCS. Frequency: 1/7. (PMID:17525139)
- Sternocleidomastoid amyotrophy (HP:0012036): Wasting of the sternocleidomastoid muscle, the muscle in the anterior part of the neck that acts to flex and rotate the head. Evidence: PCS. Frequency: 1/7. (PMID:17525139)
- Calf muscle pseudohypertrophy (HP:0003707): Enlargement of the muscles of the calf due to their replacement by connective tissue or fat. Evidence: PCS. Frequency: 3/7. (PMID:17525139)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: IEA. (OMIM:256030)
- Foot dorsiflexor weakness (HP:0009027): Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles. Evidence: PCS. Frequency: 5/7. (PMID:17525139)
- Hyperlordosis (HP:0003307): Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine. Evidence: IEA. (OMIM:256030)
- Proximal muscle weakness (HP:0003701): A lack of strength of the proximal muscles. Evidence: IEA. (OMIM:256030)
- Spinal rigidity (HP:0003306): Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion. Evidence: TAS. (OMIM:256030)
- Abnormality of the eye (HP:0000478): Any abnormality of the eye, including location, spacing, and intraocular abnormalities. Evidence: IEA. (OMIM:256030)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:256030)
- Hand clenching (HP:0001188): An abnormal hand posture in which the hands are clenched to fists. All digits held completely flexed at the metacarpophalangeal and interphalangeal joints. In prenatal sonography of the fetal clenched hand, the index finger overlaps a clenched fist formed by the other digits. The proximal interphalangeal articulation of the index finger is flexed and ulnarly deviated, and the thumb is adducted. Evidence: IEA. (OMIM:256030)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: PCS. Frequency: 1/7. (PMID:17525139)
- Generalized muscle weakness (HP:0003324): Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature. Evidence: IEA. (OMIM:256030)
- EMG: neuropathic changes (HP:0003445): The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials). Evidence: IEA. (OMIM:256030)
- Cleft palate (HP:0000175): Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). Evidence: IEA. (OMIM:256030)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. (OMIM:256030)
- 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: 2/7. (PMID:17525139)
- 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:10051637)
- Respiratory insufficiency due to muscle weakness (HP:0002747). Evidence: IEA. (OMIM:256030)
- Slender build (HP:0001533): Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones. Evidence: IEA. (OMIM:256030)
- Nemaline bodies (HP:0003798): Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces. Evidence: PCS. Frequency: 4/7. (PMID:17525139)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: IEA. (OMIM:256030)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: TAS. (OMIM:256030)
- 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: 1/7. (PMID:17525139)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: IEA. (OMIM:256030)
- Steppage gait (HP:0003376): An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again. Evidence: PCS. Frequency: 1/7. (PMID:17525139)
- Limb muscle weakness (HP:0003690): Reduced strength and weakness of the muscles of the arms and legs. Evidence: IEA. (OMIM:256030)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: IEA. (OMIM:256030)
- Weakness of facial musculature (HP:0030319): Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve). Evidence: PCS. Frequency: 6/7. (PMID:17525139)
- Abnormal rib cage morphology (HP:0001547): A morphological anomaly of the rib cage. Evidence: IEA. (OMIM:256030)
- 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: 1/7. Onset: Young adult onset (HP:0011462). (PMID:17525139)
- 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: IEA. (OMIM:256030)
- Type 1 muscle fiber predominance (HP:0003803): An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy). Evidence: IEA. (OMIM:256030)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 3/7. (PMID:17525139)
- Frequent falls (HP:0002359). Evidence: PCS. Frequency: 2/7. (PMID:17525139)
- Neck flexor weakness (HP:0003722): Weakness of the muscles involved in neck flexion (sternocleidomastoid, longus capitus, longus colli, and scalenus anterior). Evidence: IEA. (OMIM:256030)
- Myopathic facies (HP:0002058): A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness. Evidence: PCS. Frequency: 11/17. (PMID:17525139;OMIM:256030)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: IEA. (OMIM:256030)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: IEA. (OMIM:256030)
- Talipes (HP:0001883): A deformity of foot and ankle that has different subtypes that are talipes equinovarus, talipes equinovalgus, talipes calcaneovarus and talipes calcaneovalgus. Evidence: IEA. (OMIM:256030)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: IEA. (OMIM:256030)
- Easy fatigability (HP:0003388): Increased susceptibility to fatigue. Evidence: PCS. Frequency: 1/7. (PMID:17525139)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. Frequency: 1/7. (PMID:17525139)
- 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: IEA. (OMIM:256030)
- Areflexia (HP:0001284): Absence of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:256030)
- Mildly elevated creatine kinase (HP:0008180). Evidence: IEA. (OMIM:256030)
- Congenital contracture (HP:0002803): One or more flexion contractures (a bent joint that cannot be straightened actively or passively) that are present at birth. Evidence: TAS. (OMIM:256030)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: IEA. (OMIM:256030)
- Arthrogryposis multiplex congenita (HP:0002804): Multiple congenital contractures in different body areas. Evidence: TAS. (OMIM:256030)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: IEA. (OMIM:256030)
- Late-onset distal muscle weakness (HP:0003810). Evidence: TAS. (OMIM:256030)
- EMG: myopathic abnormalities (HP:0003458): The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials. Evidence: PCS. (PMID:17525139)