Chapter 05.2 Neuromuscular Disorders Flashcards
Neuromuscular disorder is caused by an abnormality of any component of the \_\_\_\_\_\_ \_\_\_\_\_\_ neuron, which includes: \_\_\_\_\_\_ \_\_\_\_\_\_ \_\_\_\_\_\_, \_\_\_\_\_\_ nerve, \_\_\_\_\_\_ junction, muscle.
Neuromuscular disorder is caused by an abnormality of any component of the lower motor neuron, which includes: anterior horn cell, peripheral nerve, neuromuscular junction, muscle.
Etiology of neuromuscular disorder may be ________, ________, or ________.
Frequently associated with systemic effects, as some of the pathologic changes may affect skeletal, smooth, and cardiac muscles, the brain, and mitochondria in multiple organs.
The most common etiology is ________. It is crucial to obtain a detailed family history and if possible to obtain diagnostic evaluation of the affected relatives.
Etiology may be progressive, acquired, or hereditary.
Frequently associated with systemic effects, as some of the pathologic changes may affect skeletal, smooth, and cardiac muscles, the brain, and mitochondria in multiple organs.
The most common etiology is genetic. It is crucial to obtain a detailed family history and if possible to obtain diagnostic evaluation of the affected relatives.
Diagnostic evaluation of a child with suspected neuromuscular disorder:
meticulous ________ ________,
detailed ________ ________,
comprehensive past medical history and surgical history,
request for additional laboratory and genetic data that may be costly and not readily available must be considered following ascertainment of developmentally appropriate assessment and history.
Diagnostic evaluation of a child with suspected neuromuscular disorder:
meticulous physical examination,
detailed family history,
comprehensive past medical history and surgical history,
request for additional laboratory and genetic data that may be costly and not readily available must be considered following ascertainment of developmentally appropriate assessment and history.
What is Duchenne and Becker muscular dystrophy?
Muscular dystrophies are a group of genetic conditions characterized by ________ muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect ________ muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males.
Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by ________. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.
Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called ________. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in many cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.
What is Duchenne and Becker muscular dystrophy?
Muscular dystrophies are a group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy). The Duchenne and Becker types of muscular dystrophy are two related conditions that primarily affect skeletal muscles, which are used for movement, and heart (cardiac) muscle. These forms of muscular dystrophy occur almost exclusively in males.
Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused by different mutations in the same gene. The two conditions differ in their severity, age of onset, and rate of progression. In boys with Duchenne muscular dystrophy, muscle weakness tends to appear in early childhood and worsen rapidly. Affected children may have delayed motor skills, such as sitting, standing, and walking. They are usually wheelchair-dependent by adolescence. The signs and symptoms of Becker muscular dystrophy are usually milder and more varied. In most cases, muscle weakness becomes apparent later in childhood or in adolescence and worsens at a much slower rate.
Both the Duchenne and Becker forms of muscular dystrophy are associated with a heart condition called cardiomyopathy. This form of heart disease weakens the cardiac muscle, preventing the heart from pumping blood efficiently. In both Duchenne and Becker muscular dystrophy, cardiomyopathy typically begins in adolescence. Later, the heart muscle becomes enlarged, and the heart problems develop into a condition known as dilated cardiomyopathy. Signs and symptoms of dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath, extreme tiredness (fatigue), and swelling of the legs and feet. These heart problems worsen rapidly and become life-threatening in many cases. Males with Duchenne muscular dystrophy typically live into their twenties, while males with Becker muscular dystrophy can survive into their forties or beyond.
What genes are related to Duchenne and Becker muscular dystrophy?
Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called ________. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells.
Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy.
Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies.
What genes are related to Duchenne and Becker muscular dystrophy?
Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin. This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers. Dystrophin may also play a role in chemical signaling within cells.
Mutations in the DMD gene alter the structure or function of dystrophin or prevent any functional dystrophin from being produced. Muscle cells without enough of this protein become damaged as muscles repeatedly contract and relax with use. The damaged fibers weaken and die over time, leading to the muscle weakness and heart problems characteristic of Duchenne and Becker muscular dystrophies. Mutations that lead to an abnormal version of dystrophin that retains some function usually cause Becker muscular dystrophy, while mutations that prevent the production of any functional dystrophin tend to cause Duchenne muscular dystrophy.
Because Duchenne and Becker muscular dystrophies result from faulty or missing dystrophin, these conditions are classified as dystrophinopathies.
How do people inherit Duchenne and Becker muscular dystrophy?
This condition is inherited in an ________-________ ________ pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In about two-thirds of cases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene. The other one-third of cases probably result from new mutations in the gene in affected males and are not inherited.
In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry a DMD gene mutation may have muscle weakness and cramping. These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males. Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including cardiomyopathy.
How do people inherit Duchenne and Becker muscular dystrophy?
This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In about two-thirds of cases, an affected male inherits the mutation from his mother, who carries one altered copy of the DMD gene. The other one-third of cases probably result from new mutations in the gene in affected males and are not inherited.
In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry a DMD gene mutation may have muscle weakness and cramping. These symptoms are typically milder than the severe muscle weakness and atrophy seen in affected males. Females who carry a DMD gene mutation also have an increased risk of developing heart abnormalities including cardiomyopathy.
ANTERIOR HORN DISORDERS IN CHILDREN: Spinal Muscular Atrophy
The SMAs comprise a group of autosomal recessive disorders characterized by progressive weakness of the lower motor neurons.
SMA type I (________ ________ or ________-________): Onset is from ________ to 6 months.
SMA type II (________ ________): Onset is between 6 and ________ months.
SMA type III (________ ________): Onset is after ________ months.
SMA type IV (________ onset): Onset is in adulthood (mean onset, mid-________).
ANTERIOR HORN DISORDERS IN CHILDREN: Spinal Muscular Atrophy
The SMAs comprise a group of autosomal recessive disorders characterized by progressive weakness of the lower motor neurons.
SMA type I (acute infantile or Werdnig-Hoffmann): Onset is from birth to 6 months.
SMA type II (chronic infantile): Onset is between 6 and 18 months.
SMA type III (chronic juvenile): Onset is after 18 months.
SMA type IV (adult onset): Onset is in adulthood (mean onset, mid-thirties).
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Presents before ________ months of age – 95% of patients have signs and symptoms by 3 months. Severe, progressive muscle weakness and ________ or reduced muscle ________.
Reports of impaired fetal movements are frequently observed.
Prolonged ________ may be noted at delivery.
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Presents before 6 months of age – 95% of patients have signs and symptoms by 3 months. Severe, progressive muscle weakness and flaccid or reduced muscle tone.
Reports of impaired fetal movements are frequently observed.
Prolonged cyanosis may be noted at delivery.
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE Clinical signs: severe limb and \_\_\_\_\_\_\_\_ weakness \_\_\_\_\_\_\_\_ posture weak cry marked \_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_ breathing \_\_\_\_\_\_\_\_-shaped chest internal rotation of arms no evidence of cerebral involvement severe nonprogressive weakness prone to \_\_\_\_\_\_\_\_ infections
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE Clinical signs: severe limb and axial weakness frog posture weak cry marked hypotonia diaphragmatic breathing bell-shaped chest internal rotation of arms no evidence of cerebral involvement severe nonprogressive weakness prone to respiratory infections
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Diagnostic workup:
________ is normal.
EMG/NCV – ________ amplitude and possibly ________ velocity in motor conduction studies, a ________ sensory conduction study, and a mild ________ in amplitude and duration of motor unit potential and fibrillation potential.
Muscle biopsy – early stages may be ________. Large group atrophy and clusters of large fibers (type I) are noted at later (6 to 8 weeks) stages.
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Diagnostic workup:
CK is normal.
EMG/NCV – decreased amplitude and possibly decreased velocity in motor conduction studies, a normal sensory conduction study, and a mild increase in amplitude and duration of motor unit potential and fibrillation potential.
Muscle biopsy – early stages may be inconclusive. Large group atrophy and clusters of large fibers (type I) are noted at later (6 to 8 weeks) stages.
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Prognosis:
________. Vast majority die within the first ________ years of life.
Treatment:
Supportive
Suctioning
SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Prognosis:
Poor. Vast majority die within the first 3 years of life.
Treatment:
Supportive
Suctioning
SMA TYPE II – CHRONIC INFANTILE FORM
Clinical signs:
The most common manifestation – developmental ________ delay between ________ and ________ months.
Unusual feature of the disease – ________ ________ affecting the fingers, attributed to fasciculations in the skeletal muscles.
May see ________ ________.
Normal–________ intellect.
Joint ________.
SMA TYPE II – CHRONIC INFANTILE FORM
Clinical signs:
The most common manifestation – developmental motor delay between 6 and 18 months.
Unusual feature of the disease – postural tremor affecting the fingers, attributed to fasciculations in the skeletal muscles.
May see tongue fasciculations.
Normal–advanced intellect.
Joint laxity.
SMA TYPE II – CHRONIC INFANTILE FORM
Diagnostic workup:
________ is normal–elevated.
EMG/NCV – ________ amplitude and possibly ________ velocity in motor conduction studies, a ________ sensory conduction study, and a mild ________ in amplitude and duration of motor unit potential and fibrillation potential.
Muscle biopsy – large group atrophy as well as clusters of large fibers (type I).
Prognosis:
The life span of patients with SMA type II varies from ________ years to the third ________ of life.
SMA TYPE II – CHRONIC INFANTILE FORM
Diagnostic workup:
CK is normal–elevated.
EMG/NCV – decreased amplitude and possibly decreased velocity in motor conduction studies, a normal sensory conduction study, and a mild increase in amplitude and duration of motor unit potential and fibrillation potential.
Muscle biopsy – large group atrophy as well as clusters of large fibers (type I).
Prognosis:
The life span of patients with SMA type II varies from 2 years to the third decade of life.
SMA TYPE III – CHRONIC JUVENILE OR KUGELBERG-WELANDER SYNDROME
Clinical signs:
Mild form of ________ ________ SMA.
Appears after age ________ months.
Characterized by slowly progressive ________ weakness.
Patients can stand and walk but have trouble with motor skills, such as going up and down stairs. This is due to weakness of hip extensors.
Diagnostic workup:
CK – normal–elevated.
EMG/NCV – decreased ________ and possibly ________ velocity in motor conduction studies, a normal ________ conduction study, and a mild ________ in amplitude and duration of motor unit potential and fibrillation potential.
Muscle biopsy – large group atrophy as well as clusters of large fibers. Also, focal small group atrophy may be seen.
SMA TYPE III – CHRONIC JUVENILE OR KUGELBERG-WELANDER SYNDROME
Clinical signs:
Mild form of autosomal recessive SMA.
Appears after age 18 months.
Characterized by slowly progressive proximal weakness.
Patients can stand and walk but have trouble with motor skills, such as going up and down stairs. This is due to weakness of hip extensors.
Diagnostic workup:
CK – normal–elevated.
EMG/NCV – decreased amplitude and possibly decreased velocity in motor conduction studies, a normal sensory conduction study, and a mild increase in amplitude and duration of motor unit potential and fibrillation potential.
Muscle biopsy – large group atrophy as well as clusters of large fibers. Also, focal small group atrophy may be seen.
SMA TYPE IV – ADULT-ONSET FORM Clinical signs: Onset after age of \_\_\_\_\_\_\_\_ years. Slowly progressive proximal weakness. Normal life expectancy.
SMA TYPE IV – ADULT-ONSET FORM Clinical signs: Onset after age of 20 years. Slowly progressive proximal weakness. Normal life expectancy.
