Chapter 05.2 Neuromuscular Disorders

Question 1

Neuromuscular disorder is caused by an abnormality of any component of the ______ ______ neuron, which includes:
______ ______ ______,
______ nerve,
______ junction,
muscle.

Answer 1

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.

Question 2

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.

Answer 2

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.

Question 3

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.

Answer 3

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.

Question 4

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.

Answer 4

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.

Question 5

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.

Answer 5

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.

Question 6

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.

Answer 6

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.

Question 7

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-________).

Answer 7

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).

Question 8

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.

Answer 8

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.

Question 9

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

Answer 9

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

Question 10

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.

Answer 10

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.

Question 11

SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Prognosis:
________. Vast majority die within the first ________ years of life.
Treatment:
Supportive
Suctioning

Answer 11

SMA TYPE I – ACUTE INFANTILE OR WERDNIG-HOFFMANN DISEASE
Prognosis:
Poor. Vast majority die within the first 3 years of life.
Treatment:
Supportive
Suctioning

Question 12

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 ________.

Answer 12

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.

Question 13

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.

Answer 13

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.

Question 14

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.

Answer 14

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.

Question 15

SMA TYPE IV – ADULT-ONSET FORM
Clinical signs:
Onset after age of ________ years.
Slowly progressive proximal weakness.
Normal life expectancy.

Answer 15

SMA TYPE IV – ADULT-ONSET FORM
Clinical signs:
Onset after age of 20 years.
Slowly progressive proximal weakness.
Normal life expectancy.

Question 16

PERIPHERAL NERVE DISORDERS
Acute Inflammatory Demyelinating Polyradiculoneuropathy.
Also known as GBS.
A primarily ________ neuropathy.
The most common cause of acute ________ paralysis in children.
An autoimmune-mediated disease with environmental triggers.
Heterogeneous condition with a number of different variants.

Answer 16

PERIPHERAL NERVE DISORDERS
Acute Inflammatory Demyelinating Polyradiculoneuropathy.
Also known as GBS.
A primarily demyelinating neuropathy.
The most common cause of acute motor paralysis in children.
An autoimmune-mediated disease with environmental triggers.
Heterogeneous condition with a number of different variants.

Question 17

PERIPHERAL NERVE DISORDERS
Acute Inflammatory Demyelinating Polyradiculoneuropathy
Clinical Presentation
Characterized by an acute ________, ________, ________ illness manifesting as ascending weakness and areflexia
Pain and dysesthesias.

Answer 17

PERIPHERAL NERVE DISORDERS
Acute Inflammatory Demyelinating Polyradiculoneuropathy.
Clinical Presentation.
Characterized by an acute monophasic, nonfebrile, postinfectious illness manifesting as ascending weakness and areflexia.
Pain and dysesthesias.

Question 18

Triggers of GBS:
______-______ virus.
______.
Enteroviruses.
Hepatitis ______ and ______.
______.
Mycoplasma pneumonia.
Campylobacter jejuni.

Answer 18

Triggers of GBS:
Epstein-Barr virus.
Cytomegalovirus.
Enteroviruses.
Hepatitis A and B.
Varicella.
Mycoplasma pneumonia.
Campylobacter jejuni.

Question 19

A variant of GBS, ______ ______ syndrome, which is characterized by the triad of ______, ______, and ______, is also linked to preceding infection with C. jejuni. Most of these patients have antibodies against the ______ ______.

Answer 19

A variant of GBS, Miller Fisher syndrome, which is characterized by the triad of ophthalmoplegia, ataxia, and areflexia, is also linked to preceding infection with C. jejuni. Most of these patients have antibodies against the GQ1b ganglioside.

Question 20

PERIPHERAL NERVE DISORDERS
Acute Inflammatory Demyelinating Polyradiculoneuropathy
Outcome
More favorable in ______ than in ______
Recurrence is relatively uncommon in children (5% to 12%)

Answer 20

PERIPHERAL NERVE DISORDERS
Acute Inflammatory Demyelinating Polyradiculoneuropathy
Outcome
More favorable in children than in adults
Recurrence is relatively uncommon in children (5% to 12%)

Question 21

Differential Diagnosis of GBS in Children
1. Botulism – In infants, botulism should be considered. Botulism is characterized not only by (______) weakness but also by involvement of the ______ muscles (______), ______ of the pupil, and constipation.
2. Myasthenia Gravis – Can be present with primarily proximal weakness in childhood. A good history, testing for acetylcholine receptor antibodies, and electrophysiologic studies with nerve conduction studies (NCSs) and EMG, including repetitive stimulation, can help to distinguish myasthenia gravis from GBS.
3. Infectious Processes – GBS-like syndromes can occur in certain infections, such as ______ disease or ______.
4. Peripheral Neuropathies – ______, glue sniffing, heavy metals, ______-______ pesticides, HIV, diphtheria, Lyme disease, inborn errors of metabolism, Leigh disease, Tangier disease, porphyria, and critical illness polyneuropathy.
5. Neuromuscular Junction Disorders – ______ paralysis, myasthenia gravis, botulism, and ______.

Answer 21

Differential Diagnosis of GBS in Children
1. Botulism – In infants, botulism should be considered. Botulism is characterized not only by (descending) weakness but also by involvement of the extraocular muscles (ophthalmoplegia), miosis of the pupil, and constipation.
2. Myasthenia Gravis – Can be present with primarily proximal weakness in childhood. A good history, testing for acetylcholine receptor antibodies, and electrophysiologic studies with nerve conduction studies (NCSs) and EMG, including repetitive stimulation, can help to distinguish myasthenia gravis from GBS.
3. Infectious Processes – GBS-like syndromes can occur in certain infections, such as Lyme disease or HIV.
4. Peripheral Neuropathies – Vincristine, glue sniffing, heavy metals, organo-phosphate pesticides, HIV, diphtheria, Lyme disease, inborn errors of metabolism, Leigh disease, Tangier disease, porphyria, and critical illness polyneuropathy.
5. Neuromuscular Junction Disorders – Tick paralysis, myasthenia gravis, botulism, and hypercalcemia.

Question 22

Pediatric Aspects of Treatment and Management of GBS
The most effective form of therapy is generally considered to be intravenous ______ (______).
______ may decrease the severity and shorten the duration of GBS.
Results of plasmapheresis and IVIG are similar, with possibly fewer side effects seen with IVIG.
In patients, care should be taken to monitor respiratory and cardiac function, especially in the acute, progressive stage of the disease.
Respiratory compromise is the most concerning and life-threatening aspect of GBS in childhood.

Answer 22

Pediatric Aspects of Treatment and Management of GBS
The most effective form of therapy is generally considered to be intravenous immunoglobulin (IVIG).
Plasmapheresis may decrease the severity and shorten the duration of GBS.
Results of plasmapheresis and IVIG are similar, with possibly fewer side effects seen with IVIG.
In patients, care should be taken to monitor respiratory and cardiac function, especially in the acute, progressive stage of the disease.
Respiratory compromise is the most concerning and life-threatening aspect of GBS in childhood.

Question 23

HEREDITARY MOTOR SENSORY NEUROPATHY
Inherited disorders of peripheral nerves, both ______ and ______.
Progressive neuromuscular impairments.
Onset usually in the first or second decade of life.

Answer 23

HEREDITARY MOTOR SENSORY NEUROPATHY
Inherited disorders of peripheral nerves, both motor and sensory.
Progressive neuromuscular impairments.
Onset usually in the first or second decade of life.

Question 24

Seven Types
Hereditary motor sensory neuropathy (HMSN) types ______ and ______ (______ inherited ______ ______ neuropathies)
HMSN type 1 (CMT type 1)
HMSN type 2 (______ inherited ______ ______) CMT type 2
HMSN type 3 (______ neuropathy of ______ [______-______])
HMSN type 4 (______ neuropathy [______] associated with ______ acid excess)
HMSN type 5 (associated with ______ paraplegia)
HMSN type 6 (with ______ atrophy)
HMSN type 7 (with ______ ______)

Answer 24

Seven Types
Hereditary motor sensory neuropathy (HMSN) types 1A and 1B (dominantly inherited hypertrophic demyelinating neuropathies) CMT type 1
HMSN type 2 (dominantly inherited neuronal neuropathies) CMT type 2
HMSN type 3 (hypertrophic neuropathy of infancy [Déjerine-Sottas])
HMSN type 4 (hypertrophic neuropathy [Refsum] associated with phytanic acid excess)
HMSN type 5 (associated with spastic paraplegia)
HMSN type 6 (with optic atrophy)
HMSN type 7 (with retinitis pigmentosa)

Question 25

The most common form of CMT1, known as ______, was associated with a duplication within chromosome ______.
The second most common form of CMT1 (CMT1B) and some cases of Déjerine-Sottas syndrome were found to be associated with mutations in the ______ ______ ______ (______) gene in chromosome ______.
Mutations of each of these genes have been associated with multiple, overlapping phenotypes. For example, myelin protein zero mutations are associated with CMT1B, Déjerine-Sottas syndrome, and the axonal CMT2 phenotype.

Answer 25

The most common form of CMT1, known as CMT1A, was associated with a duplication within chromosome 17p11.2.
The second most common form of CMT1 (CMT1B) and some cases of Déjerine-Sottas syndrome were found to be associated with mutations in the myelin protein zero (MPZ) gene in chromosome 1.
Mutations of each of these genes have been associated with multiple, overlapping phenotypes. For example, myelin protein zero mutations are associated with CMT1B, Déjerine-Sottas syndrome, and the axonal CMT2 phenotype.

Question 26

Inheritance of HMSN Disorders
CMT1 is a ______ inherited, ______, predominantly ______ form.
CMT2 is a ______ inherited predominantly ______ form.
Déjerine-Sottas is a severe form with onset in ______.
CMTX is inherited in an ______-______ manner.
CMT4 includes the various ______ ______ recessive forms of CMT disease.
CMT is nearly always slowly progressive.

Answer 26

Inheritance of HMSN Disorders
CMT1 is a dominantly inherited, hypertrophic, predominantly demyelinating form.
CMT2 is a dominantly inherited predominantly axonal form.
Déjerine-Sottas is a severe form with onset in infancy.
CMTX is inherited in an X-linked manner.
CMT4 includes the various demyelinating autosomal recessive forms of CMT disease.
CMT is nearly always slowly progressive.

Question 27

Clinical Features of HMSN Disorders
______ signs tend to develop before ______ signs.
Weakness and atrophy are first seen in intrinsic foot muscles, followed by ankle and toe dorsiflexors.
Mismatch between strength in the affected ______-innervated muscles and the less affected ______-innervated muscles results in development of typical high-arched feet, hammer toes, and difficulty with heel walking seen early in physical examination.
Sensory impairment tends to follow motor impairment and remains less severe.
Patients are more susceptible to compression neuropathies and radiculopathies.
Sprains and fractures are disabling and avoidable.

Answer 27

Clinical Features of HMSN Disorders
Motor signs tend to develop before sensory signs.
Weakness and atrophy are first seen in intrinsic foot muscles, followed by ankle and toe dorsiflexors.
Mismatch between strength in the affected peroneal-innervated muscles and the less affected tibial-innervated muscles results in development of typical high-arched feet, hammer toes, and difficulty with heel walking seen early in physical examination.
Sensory impairment tends to follow motor impairment and remains less severe.
Patients are more susceptible to compression neuropathies and radiculopathies.
Sprains and fractures are disabling and avoidable.

Question 28

Treatment of HMSN Disorders
The common foot deformities of CMT can lead to discomfort, impaired ambulation, and disability. ______ weakness and instability can be treated with ______ or ______ modifications. Moderate activity is recommended. Overexertion should be avoided.

Answer 28

Treatment of HMSN Disorders
The common foot deformities of CMT can lead to discomfort, impaired ambulation, and disability. Ankle weakness and instability can be treated with orthoses or shoe modifications. Moderate activity is recommended. Overexertion should be avoided.

Question 29

NEUROMUSCULAR JUNCTION DISORDERS
Transient Neonatal Myasthenia
It occurs in 10% to 30% of neonates born to ______ mothers.
It may occur any time during the first ______ to ______ days of life, and infants should be monitored closely for any signs of respiratory distress.
If treated and monitored, it is a self-limiting condition in vast majority of the cases.
The major cause is ______ transfer of circulating ______ antibodies from mother to fetus.

Answer 29

NEUROMUSCULAR JUNCTION DISORDERS
Transient Neonatal Myasthenia
It occurs in 10% to 30% of neonates born to myasthenic mothers.
It may occur any time during the first 7 to 10 days of life, and infants should be monitored closely for any signs of respiratory distress.
If treated and monitored, it is a self-limiting condition in vast majority of the cases.
The major cause is transplancental transfer of circulating acetylcholine antibodies from mother to fetus.

Question 30

NEUROMUSCULAR JUNCTION DISORDERS
Congenital or Infantile Myasthenia.
Occurs in infants of ______ mothers and may have an autosomal recessive inheritance. Antibodies to ______ receptor are usually absent.

Answer 30

NEUROMUSCULAR JUNCTION DISORDERS
Congenital or Infantile Myasthenia.
Occurs in infants of nonmyasthenic mothers and may have an autosomal recessive inheritance. Antibodies to ACh receptor are usually absent.

Question 31

NEUROMUSCULAR JUNCTION DISORDERS
Juvenile Myasthenia
Juvenile myasthenia gravis has a similar pathophysiologic origin as adult myasthenia gravis, but there are important differences, mostly relating to epidemiology, presentation, and therapeutic decision making.
Several considerations should be emphasized, such as postponement of ______ therapy from an early age, which is associated with growth retardation, and avoidance of thymectomy due to the risks of induced ______.
It particularly affects ______ girls and is severe and ______ in presentation. Clinically presents with weakness of other muscles including facial and mastication. It can affect swallowing, speech, respiration as well as neck, trunk, and limb muscles.

Answer 31

NEUROMUSCULAR JUNCTION DISORDERS
Juvenile Myasthenia
Juvenile myasthenia gravis has a similar pathophysiologic origin as adult myasthenia gravis, but there are important differences, mostly relating to epidemiology, presentation, and therapeutic decision making.
Several considerations should be emphasized, such as postponement of corticosteroid therapy from an early age, which is associated with growth retardation, and avoidance of thymectomy due to the risks of induced immunodeficiency.
It particularly affects adolescent girls and is severe and labile in presentation. Clinically presents with weakness of other muscles including facial and mastication. It can affect swallowing, speech, respiration as well as neck, trunk, and limb muscles.

Question 32

MYOPATHIES
Facioscapulohumeral Muscular Dystrophy (FSHD)
Slowly progressive dystrophic myopathy.
Predominant involvement of ______ and ______ girdle musculature.
Autosomal dominant inheritance; 10% to 30% is caused by sporadic mutation.
Presents before age 20 years.
Serum CK levels are ______ or slightly elevated in the majority of patients.
Diagnosis – confirmed in more than 90% by molecular genetic testing.

Answer 32

MYOPATHIES
Facioscapulohumeral Muscular Dystrophy (FSHD)
Slowly progressive dystrophic myopathy.
Predominant involvement of facial and shoulder girdle musculature.
Autosomal dominant inheritance; 10% to 30% is caused by sporadic mutation.
Presents before age 20 years.
Serum CK levels are normal or slightly elevated in the majority of patients.
Diagnosis – confirmed in more than 90% by molecular genetic testing.

Question 33

MYOPATHIES
Clinical Presentation
______ weakness.
Difficulties with ______ closure.
______ appearance.
______ stabilizers, shoulder ______, and shoulder ______ rotators are affected.
______ are spared if tested with scapulae stabilized.
Contractures of joints are ______.
Scoliosis is mild and ______.
Evidence for mild restrictive lung disease in 50% of patients.

Answer 33

MYOPATHIES
Clinical Presentation
Facial weakness.
Difficulties with eye closure.
Expressionless appearance.
Scapular stabilizers, shoulder abductors, and shoulder external rotators are affected.
Deltoids are spared if tested with scapulae stabilized.
Contractures of joints are uncommon.
Scoliosis is mild and nonprogressive.
Evidence for mild restrictive lung disease in 50% of patients.

Question 34

Coates syndrome – early onset of ______ characterized by ______ ______ deficit and progressive ______ ______ of the ______.
Rapid in progression.

Answer 34

Coates syndrome – early onset of FSHD characterized by sensorineural hearing deficit and progressive exudative telangiectasia of the retina.
Rapid in progression.

Question 35

EMERY-DREIFUSS MUSCULAR DYSTROPHY (EMD)
Characterized by
______.
______.
______ ______ abnormalities.

Answer 35

EMERY-DREIFUSS MUSCULAR DYSTROPHY (EMD)
Characterized by
Weakness.
Contractures.
Cardiac conduction abnormalities.

Question 36

EMERY-DREIFUSS MUSCULAR DYSTROPHY (EMD)
EMD-1
______-______ ______ progressive dystrophic myopathy.
Typically presents in the ______ decade of life but age of presentation may vary.
Evolving contractures are more limiting than weakness.
______ flexion contractures are a hallmark of disease.
Functional limitations with ambulation and stair negotiation. However, due to slow progression, loss of ambulation is rare.
Progressive cardiac disease is almost invariably present with onset in the early second decade to the fourth decade.
Arrhythmia may lead to emboli or sudden death, cardiomyopathy leads to progressive left ventricular myocardial dysfunction.

Answer 36

EMERY-DREIFUSS MUSCULAR DYSTROPHY (EMD)
EMD-1
X-linked recessive progressive dystrophic myopathy.
Typically presents in the second decade of life but age of presentation may vary.
Evolving contractures are more limiting than weakness.
Elbow flexion contractures are a hallmark of disease.
Functional limitations with ambulation and stair negotiation. However, due to slow progression, loss of ambulation is rare.
Progressive cardiac disease is almost invariably present with onset in the early second decade to the fourth decade.
Arrhythmia may lead to emboli or sudden death, cardiomyopathy leads to progressive left ventricular myocardial dysfunction.

Question 37

EMERY-DREIFUSS MUSCULAR DYSTROPHY (EMD)
EMD-2
Abnormality due to ______ A/C protein linked to chromosome 1q21.2.
Inheritance may be dominant or ______ or ______.
Missense mutation leads to childhood onset.
Clinical feature is scapuloperoneal and facial distribution of weakness.
Contractures are rare.

Answer 37

EMERY-DREIFUSS MUSCULAR DYSTROPHY (EMD)
EMD-2
Abnormality due to lamin A/C protein linked to chromosome 1q21.2.
Inheritance may be dominant or recessive or missense.
Missense mutation leads to childhood onset.
Clinical feature is scapuloperoneal and facial distribution of weakness.
Contractures are rare.

Question 38

CONGENITAL MYOPATHIES
A group of heterogeneous disorders usually presenting with ______ ______ due to genetic defects, causing primary myopathies with the absence of any structural abnormality of the central nervous system or peripheral nerves.

Answer 38

CONGENITAL MYOPATHIES
A group of heterogeneous disorders usually presenting with infantile hypotonia due to genetic defects, causing primary myopathies with the absence of any structural abnormality of the central nervous system or peripheral nerves.