Reduced strength and weakness of the muscles of the arms and legs.

Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the knee joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.

Difficulty in swallowing.

Absence of neurologic reflexes such as the knee-jerk reaction.

The term gait disturbance can refer to any disruption of the ability to walk.

A type of Developmental delay characterized by a delay in acquiring motor skills.

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.

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.

The presence of an abnormal lateral curvature of the spine.

A lack of strength of the proximal muscles.

Reduced ability to climb stairs.

Decreased strength of the neck musculature.

A contracture of the Achilles tendon.

Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve).

Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.

A limitation in the passive range of motion of the elbow resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin.

Generalized (unlocalized) atrophy affecting muscles of the limbs in both proximal and distal locations.

Weakness of the muscles involved in neck flexion (sternocleidomastoid, longus capitus, longus colli, and scalenus anterior).

Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs).

An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.

Congenital myopathy-1B (CMYO1B) is an autosomal recessive disorder of skeletal muscle characterized by severe hypotonia and generalized muscle weakness apparent soon after birth or in early childhood with delayed motor development, generalized muscle weakness and atrophy, and difficulty walking or running. Affected individuals show proximal muscle weakness with axial and shoulder girdle involvement, external ophthalmoplegia, and bulbar weakness, often resulting in feeding difficulties and respiratory insufficiency. Orthopedic complications such as joint laxity, distal contractures, hip dislocation, cleft palate, and scoliosis are commonly observed. Serum creatine kinase is normal. The phenotype is variable in severity (Jungbluth et al., 2005; Bharucha-Goebel et al., 2013). Some patients show symptoms in utero, including reduced fetal movements, polyhydramnios, and intrauterine growth restriction. The most severely affected patients present in utero with fetal akinesia, arthrogryposis, and lung hypoplasia resulting in fetal or perinatal death (McKie et al., 2014). Skeletal muscle biopsy of patients with recessive RYR1 mutations can show variable features, including multiminicores (Ferreiro and Fardeau, 2002), central cores (Jungbluth et al., 2002), congenital fiber-type disproportion (CFTD) (Monnier et al., 2009), and centronuclear myopathy (Wilmshurst et al., 2010). For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (117000).

Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

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.

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.

Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers

An increased volume of the endomysium, which is a connective tissue sheath that surrounds each muscule fiber. Together, bundles of muscle fibers form a fasciculus, surrounded by another layer of connective tissue called the perimysium.

Multiple small zones of sarcomeric disorganization and lack of oxidative activity (known as minicores) in type 1 and type 2 muscle fibers.

An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.

A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.

An abnormal reduction in the amount of air a person can expel following maximal inspiration.

An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Any deviation from the normal circulating creatine kinase concentration.

A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.

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).

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).