Neuromuscular Disorders Flashcards
1
Q
three most common initial presentations of a child with a neuromuscular disorder
A
- floppy infant
- delayed walking
- frequent falls
2
Q
other presentations of a child with a neuromuscular disorder
A
- Fatigue
- Diplopia - double vision
- Feeding problems
- Respiratory symptoms
- Cardiac symptoms
- Cramps
- Contractures - limitations in joint range of movement
- Pain - particularly in neuropathy
- Rash
- Dysmorphic features - unusual physical features
3
Q
what is the first step in diagnosing a child with a neuromuscular disorder
A
- evaluation of the child and a description of observed patterns.
- this comes from a good history and examination.
- tentative diagnoses can be made based on clinical examinations.
4
Q
unusual patterns in a child presenting possibly presenting with a neuromuscular disorder
A
- predominantly upper limb involvement
- primarly distal symptoms as opposed to proximal symptoms
- assymmetrical symptom presentation
5
Q
functional aspects to look for in an assessment
A
are the symptoms primarily:
- weakness
- sensory impairment
- autonomic dysfunction
6
Q
anatomical considerations in a clinical examination
A
- arms vs legs vs cranial involvement
- proximal vs distal symptoms
- symmetric vs asymmestric presentation
7
Q
temporal characteristics to identify in a clinical examination
A
- acute vs chronic vs episodic
- hereditary?
- fluctuation of symptoms?
- does fatigue affect symptoms?
- age of onset
8
Q
main diagnostic approaches for neuromuscular disorders
A
- creatine kinase levels
electrodiagnostic tests - imaging (ultrasound and MRI)
- genetic testing
- muscle biopsy
9
Q
creatine kinase level testing
A
- Easy biochemical test.
- Enzyme present in all muscles.
- Elevated levels can indicate certain neuromuscular disorder.
10
Q
types of electrodiagnostic tests used to diagnose neuromuscular conditions
A
- Nerve conduction studies.
- Electromyography.
- Repetitive nerve stimulation (e.g. evaluating neuromuscular junction.)
11
Q
how is imaging used in diagnosis of neuromuscular disorders
A
- Evaluate muscle patterns.
- Useful in some congenital myopathies
12
Q
what type of genetic testing can be used to diagnose neuromuscular disorders
A
- depends on the disorder
- some disorders can be diagnosed based on single gene testing
- others (e.g. congenital myopathies and congenital muscular dystrophies) may require a genetic panel
13
Q
why are we moving away from including muscle biopsies in diagnosing neuromusuclar disorders
A
invasive
14
Q
example of a spinal cord disorder
A
Freidrich’s ataxia
15
Q
describe the aetiology of FA
A
- Caused by intronic GAA expansion in Frataxin gene (1996).
- The first intron in the frataxin gene becomes abnormally expanded resulting in the silencing of the gene and reducing frataxin production.
- Reduced frataxin expression leads to mitochondrial dysfunction.
- Frataxin is involved in iron sulphite clustering in the mitochondria.
- Mitochondria are localised in body regions but particularly in the spinocerebellar tracts, the dorsal root ganglion and the dorsal columns.
- Can be some involvement in motor tracts (pyramidal tracts).
- Basically, Freidrich’s ataxia is caused by lack of frataxin leading to degeneration of the posterior columns of the spinal cord.
- It is an autosomal recessive inheritance disease.
16
Q
is freidrich’s ataxia the most common hereditary ataxia
A
yes
17
Q
prevalence of freirich’s ataxia
A
1/50,000
18
Q
carrier rate of friedrich’s ataxia
A
1/120
19
Q
ratio of males to females affected by friedrich’s ataxia
A
1:1
20
Q
what race is most commonly affected by friedrich’s ataxia
A
white people
21
Q
what type of ataxia is freidrich’s ataxia
A
sensory and cerebellar
22
Q
what causes the sensory type ataxia
A
feedback of sensory and proprioceptive systems are impaired
23
Q
what causes the cerebellar type ataxia in friedrich’s ataxia
A
the spinocerebellar involvement
24
Q
why is there loss of deep tendon reflexes in friedrich’s ataxia
A
due to involvement of the dorsal root ganglion
25
what does the involvement of the dorsal root ganglion in friedrich's ataxia cause
loss of deep tendon reflexts
26
why is there an upgoing plantar response in friedrich's ataxia
due to corticospinal tract involvement
27
what does corticospinal tract involvement cause in friedrich's ataxia
upgoing plantar response
28
what causes progressive kyphoscoliosis in friedrich's ataxia
a spinal muscular imbalance
29
what does a spinal muscular imbalance cause in friedrich's ataxia
progressive kyphoscoliosis
30
what cranial nerves are commonly affected in friedrich's ataxia
VN VII, X and XII
31
what does involvement of CN VII, X and XII in friedrich's ataxia cause
bulbar signs such as facial weakness, dysarthria and dysphagia
32
what is the age of onset of friedrich's ataxia
late childhood and early adolescence
33
what is usually the presenting symptom of friedrich's ataxia
- Symmetric **gait ataxia i**s usually the **presenting symptom**.
- Gait is **broad-based** with **constant shifting** to maintain balance.
- This type of gait is known as **ataxic gait**.
34
describe the development of ataxia in friedrich's ataxia
- Ataxia development is **insidious** and usually begins with **difficulty standing and running**.
- Attempts to correct imbalances usually result in **wild or uncontrolled movements**.
- As the disease progresses, the ataxia ascends to affect the **trunk and arms**.
- **Titubation** while sitting and standing may be noted.
- As the ataxia develops to affect the arms patients develop **action and intention tremors** and display **choreiform movements**.
- They may also have **buccal and facial tremors**.
- Patients will eventually **lose ambulation** after 10-15 years.
35
signs of friedrich's ataxia that may be noted on a muscoskeletal exam
- Progressive limb and gait ataxia.
- Truncal ataxia.
- Motor weakness.
- Loss of muscle tone.
- Muscular atrophy.
- Pes cavus.
- Kyphoscoliosis.
36
signs of friedrich's ataxia that may be noted on a neurological exam
- Hyporeflexia or areflexia
- Decreased or absent deep tendon reflexes.
- Extensor plantar responses.
- Sensory neuropathy.
- Loss of two-point discrimination.
- Loss of proprioception and vibration.
- Loss of pain and temperature sensation.
- Dysmetria.
- Urinary urgency or incontinence.
- Loss of visual acuity.
- Horizontal nystagmus (particularly with lateral gaze).
- Abnormal extra-ocular movements.
- Abnormal visual evoked potentials (reduced amplitude and delayed latency).
- Sensorineural hearing loss.
- Vertigo.
37
signs of friedrich's ataxia that may be noted on a psychological exam
- Mild executive dysfunction.
- Emotional lability.
38
signs of friedrich's ataxia that may be noted on a cardiovascular exam
- Cardiomegaly - enlarged heart.
- Tachycardia.
- Atrial fibrillation.
39
dysarthria in friedrich's ataxia
- slow, jerky speech, sudden utterances, eventual near-unintelligibility.
- Usually develops in teenage years and progresses from there.
40
swallowing difficulties in friedrich's ataxia
- Liquids worsen with disease progression.
- Advanced disease: choking risk, need for modified foods.
- Possible nasogastric tube or gastrostomy feeding.
41
testing for friedrich's ataxia
genetic testing and imaging
42
genetic testing for friedrich's ataxia
- FA is the only disease with pathological GAA repeats.
- Single gene testing is therefore appropriate.
43
imaging for friedrich's ataxia
- MRI is the preferred modality for evaluation of the extent of atrophic changes.
- MRI of the brain and spinal cord to show atrophy of cervical/thoracic spinal cord and cerebellum.
44
treatment options for friedrich's ataxia
- Antioxidants.
- Enhancers of energy metabolism
- Iron chelators.
- Erythropoietin.
- Immune modulators.
- Histone deacetylase inhibitors (HDAG).
- Repeat targeted nucleic acids.
- Management of associated symptoms (e.g., cardiomyopathy, diabetes, scoliosis).
45
physiotherapy in friedrich's ataxia
- Main recommendation to delay disease progression and preserve function.
- Main goal is to strengthen posture and encourage muscle use.
46
occupational therapy in friedrich's ataxia
focuses on maintaining independence
47
surgery in friedrich's ataxia
spinal fusion surgery can correct kyphosoliosis
48
what predicts rapid progression in freidrich's ataxia
early onset and left ventricular hypertrophy
49
does early onset and left ventricular hypertrophy predict rapid or slow progression in friedrich's ataxia
rapid progression
50
what shortens life expectancy in friedrich's ataxia
neurological impairment and cardiomyopathy
51
what is the most frequent cause of death in friedrich's ataxia
cardiac dysfunction such as congestive heart failure and arrythmia
52
does symptomatic treatment have an effect on life expectancy in friedrich's ataxia
yes, symptomatic treatment improves life expectancy
53
are there any treatments currently available to halt degenerative progression of friedrich's ataxia
no
54
example of an anterior horn cell disorder
SMA
55
what does SMA stand for
Spinal Muscular Atrophy
56
What is SMA
a collection of inherited clinical syndromes causing degeneration of anterior horn cells (i.e. motor neuros) in the spinal cord leading to associated destruction of motor cells and presenting clinically with proximal muscle weakness and atrophy
57
incidence of SMA
1 in 6000-11000
58
what is earlier age of onset of SMA associated with
poorer function and prognosis
59
what are SMA subtypes determined by
- age of onset
- clinical severity
- life expectancy
60
what type of inheritance is SMA
autosomal recessive
61
aeitology of SMA
- 95% of cases are caused by a homozygous deletion of SMN1 gene on chromosome 5q13.
- this causes a loss of motor neurons which leads to grouped fibre atrophy
62
what does SMN1 produce
Survival Motor Neuron protein
63
what is SMN2
a backup gene which also produces SMN proteins but only 10% of proteins produced by SMN2 are functional
64
what is the typology of SMA due to
| (from a pathophysiological perspective)
the number of SNM2 copies - the more copies the more backup SMN2 gene that can be produced and the less severe the clinical phenotype
65
onset of SMA type 0
congenital
66
symptoms of SMA type 0
- Hypotonia.
- Early respiratory failure.
- Severe weakness.
- Decreased fetal movements.
67
survival of SMA type 0
< 1 month
68
another name for SMA type I
Werdnig=Hoffman Disease
69
onset of SMA type I
< 6 months
70
symptoms of SMA type I
- Proximal wasting and weakness disproportionately affecting legs over arms (frog leg posture).
- Areflexia.
- Scoliosis.
- Typical cognition.
- Tongue fasciculations
- Limited head control.
- Never achieves sitting milestone.
- Respiratory failure.
- Intercostal muscle weakness but sparing of diaphragm leads to paradoxical breathing and a parasol or bell shaped chest.
- Bulbar Denervation leading to dysfunction → nutritional failure.
71
survival of SMA type I
< 2 years
72
onset of SMA type II
6-18 months
73
symptoms of SMA type II
- Proximal wasting and weakness disproprotionately affecting legs over arms.
- Areflexia.
- Scoliosis.
- Typical cognition.
- Tongue fasciculations.
- Tremors.
- Can sit but cannot stand.
- Progressive respiratory failure.
- Nutritional failure.
74
survival of SMA type II
30s/40s
75
onet of SMA type III
> 18 months
76
symptoms of SMA type III
- Will stand and walk.
- Proximal weakness disproportionately affecting legs over arms.
- Do not typically suffer from restrictive lung disease.
- Resembles muscular dystrophy.
77
survival of SMA type III
compatible with a normal lifespan
78
diagnostic approaches for SMA
- genetic testing
- creatine kinase levels
- nerve conduction studies
- needle electromyography (EMG)
- musle biopsy
79
genetic testing in SMA
- PCR or MLPA testing detects SMN1 deletion with with 95% sensitivity.
- SMN2 detection is usually performed at the same time as a prognostic indicator.
80
creatine kinase level findings in a patient with SMA
normal but may be slightly elevated
81
nerve conduction study findings in a patient with SMA
- Sensory nerves demonstrate normal action potentials.
- Motor nerves may show diminished action potentials.
82
needle electromyography findings in a patient with SMA type I
denervation changes without reinnervation.
83
needle electromyography findings in a patient with SMA II/III
neurogenic patterns (action potentials with prolonged duration, increased amplitude and diminished recruitment).
84
muscle biopsy findings in a patient with SMA
neurogenic patterns
85
when is the best time to treat a patient with SMA
presymptomatically
86
two disease-altering treatments for SMA in testing presently
- nusinersin
- gene therapy
87
brand name for nusinersen
Spinraza
88
how does nusinersen work
upregulates SMN2 gene to produce more SMN protein
89
class of function of nusinersen
antisense oligconucleotide
90
how is nusinersen delivered
intrathecally (via lumbar puncture) 3 times a year
91
example of a study which examined nusinersin
NURTURE study
92
NURTURE study findings
- 100% survival rate (25 infants).
- Improved motor function scores.
- CHOP INTEND (physiotherapy outcome measure).
- Lower need for respiratory intervention.
93
how does gene therapy work
- Treatment delivered through a virus vector - **A-AV9 virus** (a genetically modified organism).
- Replication material of A-AV9 is removed and the A-AV9 is able to **package SMN1 gene**.
- This is **infused** into the child over **60 mins**.
- The virus disseminates systemically to allow **SNM production.**
94
advantage of gene therapy over nuinersen
gene therapy is a once-off treatment which has sustained efficacy and effect, unlike nusinersen which is required 3 times a year for maintenance of effect
95
example of a study examining gene therapy for SMA
STR1VE Trial
96
considerations when evaluating neuropathy
- anatomical sites
- peripheral nerve types and fibre sizes
- pattern of peripheral nerve involvement
- course of disease
- age of first symptom onset
- electrodiagnostic features
- associated clinical features
97
anatomical sites
| neuropathy considerations
- Cranial nerves
- Plexus
- Sensory ganglia.
- Nerve roots.
- Motor neuron.
- Peripheral nerves.
98
peripheral nerve types and fibre sizes involved
| neuropathy considerations
- Motor.
- Sensory large fibre → vibration, proprioception, two-point discrimination.
- Sensory small fibre → pain, temperature, light touch.
- Autonomic.
99
pattern of peripheral nerve involvement
| neuropathy considerations
- Polyneuropathy.
- Mononeuropathy.
100
course of disease
| neuropathy considerations
- Acute.
- Chronic.
101
electrodiagnostic features
| neuropathy considerations
- Axonal versus demyelinating.
- Uniform versus nonuniform.
102
associated clinical features
| neuropathy considerations
- Non-neurological symptoms.
- Central nervous system involvement (developmental delay, seizures, psychosis).
- Concomitant diseases (autoimmune disease, mitochondrial disease).
- Toxin/medication exposures.
- Family history.
103
types of acquired neuropathy
- guillain barre syndrome
- CIDP
- metabolic
- toxic
104
guillain barre syndrome subtypes
- AIDP
- AMAN
- AMSAN
- Miller Fisher Syndrome
105
what does AIDP stand for
acquired immune demyelinating polyneuropathy
106
what does AMAN stand for
acute motor axonal neuropathy
107
what does AMSAN stand for
acute motor and sensory axonal neuropathy
108
what is miller fisher syndrom characterised by
cranial nerve involvement
109
symptoms of miller fisher syndrome
- Eye movement abnormalities.
- Opthalamoplegia.
- Ataxia.
- Areflexia.
110
what does CIDP stand for
chronic inflammatory demyelinating polyneuropathy
111
metabolic causes of acquired neuropathy
lisosomal or mitochondrian disorders
112
hereditary causes of neuropathy
- congenital
- HMSN
- HMN
- HSN
- Friedrich's ataxia
113
what does HMSN stand for
hereditary motor and sensory neuropathy
114
what does HMN stand for
hereditary motor neuropathy
115
what does HSN stand for
hereditary sensory neuropathy
116
incidence of Guillain Barré syndrome
0.4-2 per 100,000
117
are males or females affected more commonly by guillain barre syndrome
males
118
aetiology of guillain barre syndrome
- Post-infectious, immune-mediated neuropathy.
- Most common infections linked to GBS are **gastrointestinal or respiratory** illnesses
119
clinical features of guillain barre syndrome
- Symmetric distal, flaccid limb weakness (legs > arms).
- Cranial nerve involvement.
- Depressed reflexes.
- Autonomic instability.
- Pain & paresthesias.
- Respiratory involvement (affected diaphrenic nerves)
120
course of guillain barre syndrome
- Ascending weakness.
- Non-length dependent sensory symptoms.
- Progression over days to 4 weeks and then plateaus, and possibly improves.
- Monophasic - i.e. non-relapsing.
121
diagnostic tests used for guillain barre syndrome
- nerve conduction studies
- spinal tap
122
nerve conduction study findings in a patient with guillain barre syndrome
slow conduction
123
spinal tap findings in a patient with guillain barre syndrome
elevated CSF protein but normal cell count
124
treatment for guillain barre syndrome
- IV Immunoglobulin (IVIG)
- Plasma exchange.
- Supportive care (respiratory & autonomic monitoring, pain management, rehabilitation).
125
what percentage of people become nonambulant in the course of guillain barre syndrome
60%
126
what percentage of people require respiratory support in the course of guillain barre syndrome
20%
127
when is peak disease severity in guillain barre syndrom
2 weeks
128
recovery of guillain barre syndrome
90% achieve full recovery within 1-4 months
129
what is HMSN
Group of genetically mediated disorders resulting in difficulty producing proteins involved in development of myelin or axonal function.
130
what is the most common type of HMSN
Charcot Marie Tooth Disease (CMT)
131
aeitiology of CMT
- **Demyelinating** type of neuropathy caused by a **duplication** in the **PMP22 gene.**
- Gene makes **PMP22 protein** which has involvement in **maintaining function and integrity** of **myelin.**
132
most common subtype of CMT
CMT1A
133
symptoms of CMT
Presents with symmetric, slowly progressing distal weakness and wasting, depressed DTRs and sensory symptoms.
134
are communication and swallow difficulties common in CMT
no
135
most common axonal cause of HMSN
pathogenic variant in a mitochondrial gene called the mitofusin2 gene.
136
presentation of MFN2 type HMSN
more severe involvement of lower extremities than upper, and more prominent motor deficits than sensory.
137
two types of neuromuscular junction disorder
acquired and congenital
138
examples of acquired neuromuscular junction disorders
- autoimmune myaesthenia gravis
- transient neonatal myaesthenia gravis
- infantile botulism
139
how does the NMJ work
- **Action potential** propagates down the nerve causing **voltage-gated calcium channels** to open and **calcium to flow** into the nerve terminal.
- This incudes release of **acetylcholine** into **neuromuscular junction**.
- Ach diffuses across the junction and **binds with receptors**.
- This induces a change in the configuration of the receptor to **allow potassium and sodium** to flow across the **voltage-gated channel.**
- Causing **further action potentials to propagate** and a chain of events leading to **muscular contraction.**
140
what happens to the NMJ in autoimmune myaesthenia
- **Antibodies** attack the Ach receptors.
- **Prevents Ach from bindin**g to the receptors.
- **Inhibits** muscle activation.
- Leads to **muscle weakness**.
141
which two antibodies can cause myaesthenia gravis
- Acetylcholine receptor (AChR antibody)
- Muscle specific tyrosine kinase (MuSK antibody)
142
symptoms of MG caused by AChR antibody
occular and generalised
143
symptoms of MG caused by MuSK antibody
bulbar and respiratory
144
symptoms of MG
- Fatigue (exacerbated by exercise, feeding).
- Isolated ptosis & ocular weakness (100%).
- Facial weakness.
- Generalized proximal weakness.
145
how is MG diagnosed
- *AChR* & *MuSK* antibodies testing.
- Repetitive nerve stimulation
146
repetitive nerve stimulation testing for MG
looks for decrement of the repetitive CMAP amplitude when the nerve is stimulated at 3Hz.
147
treatments for MG
- Pyridostigmine - inhibits breakdown of Ach in the NMJ
- Prednisolone
- Immunosuppressants
- Plasma exchange
- Ventilatory support
- Thymectomy - can help patients achieve remission.
148
what causes neonatal transient myeasthenia gravis
affected mothers' antibodies travel across the placenta and affect the infant
149
presentation of infants with transient neonatal MG
- weak and flopping
- feeding difficulties
- sometimes foetal akinesia in utero
150
course of transient neonatal MG
antibodies disappear and child goes into remission within 1-6 weeks after birth
151
causes of infantile botulism
- **Botulism toxin**s are produced by different organisms.
- Infantile botulism can occur due to **exposure to botulism spores** in honey pet turtles.
- Botulism spores **germinate in the gut** and **produce botulism toxins**.
152
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impact of infantile botulism on the NMJ
- Disorder of **presynaptic** NMJ.
- Botulism toxins **bind to the voltage-gated calcium channels** on the presynaptic cleft.
- Prevents **release of Ach** into the NMJ.
153
treatment of infantile boltulism
a specific immunoglobulin
154
presentation of infantile botulism
suddenly floppy, respiratory failure, fixed dilated pupils, constipation.
155
what are congentital myaesthenic syndromes
- **Heterogenous** group of genetic diseases.
- Caused by **dysfunction** of **nueromuscular transmission.**
- Muscle weakness is **increased by exertion**
156
onset of CMS
infancy or childhood
157
is CMS less or more common than autoimmune MG
less common
158
prevalence of CMS in europe
1 in 500000
159
how many genetic causes of CMS are there
over 20
160
what percentage of CMS cases are presynaptic (ChAT deficiency)
5%
161
what percentage of CMS cases are synaptic (QOLQ mutation)
10%
162
what percentage of CMS cases are post synaptic (AChR mutations)
85%
163
symptoms of CMS
- Hypotonia.
- Ophthalmoplegia.
- Ptosis.
- Dysphonia.
- Dysphagia.
- Facial paresis.
- Muscle fatigability.
- Myopathic symptoms.
- Amyotrophy.
- Tendinous retractions.
- Facial malformations.
- Scoliosis.
164
what symptom of CMS is associated with mortality
acute respiratory failure
165
inheritance pattern of most CMS
autosomal recessive
166
inheritance pattern of slow channel CMS
autosomal dominant
166
course of CMS
- Transient worsening with or without return to previous status.
- Regularly progressive deterioration or improvement.
- Stability.
- Course may change at various life stages.
- Triggers: infections, pregnancy, menstrual periods.
- Worsening in adulthood.
- Favorable progression in childhood after severe neonatal course.
167
types of myopathies
- congenital
- inflammatory
- metabolic
168
example of an inflammatory myopathy
dermatoyositis
169
examples of metabolic myopathies
- pompe
- mitochondrial
- McArdles
170
examples of muscular dystrophies
- Duchenne
- FSHD
- Myotonic
- Congenital
- Limb Girdle
171
onset of clinical myopathies
birth
172
symptoms of clinical myopathies
hypotonia and weakness
173
course of clinical myopathies
static or slowly progressive
174
subtypes of clinical myopathies
- nemaline myopathy
- core myopathy
- centronuclear myopathy
175
nemaline myopathy histology
presence of nemaline rods
176
core myopathies histology
appearance of cores
177
centronuclear myopathies histology
central orientation of nuclei
178
example of a centronuclear myopathy
XL MTM1 (myotubular myopathy)
179
what type of myopathy is this
nemaline myopathy
180
what type of myopathy is this
core myopathy
181
what type of myopathy is this
centronuclear myopathy
182
neonatal and infantile clinical features of clinical myopathies
- Facial weakness.
- Ophthalamoplegia.
- Facial dysmorphism.
- Bulbar weakness.
- Severe hypotonia
- Respiratory weakness at birth.
- Ortheopaedic deformaties.
183
clinical features of older children with clinical myopathies
- Scoliosis.
- Rigid spine.
- Cardiomyopathy.
- Pes Cavus.
- Malignant Hyperthermia.
- Respiratory involvement.
184
cause of congenital muscular dystrophy
Occur as a result of genetic disorders affecting the sarcolemma of the muscle fibre.
185
are muscular dystrophies more or less progressive than myopathies and why
More progressive than myopathies due to their causing of dystrophic and necrotic muscle fibres which break down under stress due to structural failure of the sarcolemma.
186
other names for collagen 6 muscular dystrophy
Bethlehem or ullrich
187
presentation of collagen VI muscular dystrophy
muscle weakness, motor delay, hyperlax distalpharyngeal joints, rash - hyperkeratosis pylori, feeding difficultie
188
symptoms of LMNA a/z muscular dystrophy
neck flexion weakness & spinal rigidity
189
symptom of SEPN1 muscular dystrophy
spinal rigidity
190
another name for LAMA2 muscular dystrophy
merosin negative muscular dystrophy
191
LAMA2 (merosin negative muscular dystrophy) symptoms
- Joint contractures of elbows, wrists, hamstrings and knees.
- Sit but never walk.
- Muscle enzyme is elevated.
192
what is LAMA2 (merosin negative muscular dystrophy) associated with
| cogition
a white matter disorder leading to cognitive and learning disabilities
193
what does the POMT2 mutation also cause
cysts in the cerebellum
194
symptoms of myotonic dystrophy
- Weakness
- Myotonia.
- Cardiomyopathy and heart arryhthmia.
- Cataracts especially in adults.
- Respiratory, GI and endocrine involvement.
195
when can myotonic dystrophy present
- congenitally
- in childhood
- in adults
196
what is the cause of congenital myotonic dystrophy
results from an affected parent (usually the mother)
197
symptoms of congenital myotonic dystrophy
- Polyhydramnois.
- Reduced fetal movements.
- Hypotonia.
- Talipes.
- Failure to thrive.
- Developmental delay.
- Delayed walking.
- Speech delay.
198
what is the most important feature of congenital myotonic dystrophy
40-90% of patients will have ID - IQ of 40-80
199
what gene is implicated in Duchenne Muscular Dystrophy
the dystrophin gene which sits on the x chromosome
200
what does the dystrophin gene do
produces the dystrophin protein which acts as a shock absorber
201
what occurs in muscle when there is a reduction or absence of dystrophin
- Failure of production of the protein results in **breakdown of muscle fibre**, inducing **inflammation and degeneration** of muscle fibres.
- The muscle can build back up again but will be broken down in a **vicious cycle**.
- Continued cycle of **muscle fibre inflammation, degerneation and regeneration** ultimately results in aggressive muscle **weakness, wasting, scarring**.
202
cause of Duchenne Muscular Dystrophy
absence of dystrophin production in msucle fibres due to a deletion of the dystrophin gene in exons 48-50
this is an out-of-frame deletion meaning genetic code is disrupted and the protein is not produced
203
two key signs of Duchenne Muscular Dystrophy
- Muscular hypertrophy (particularly in the calves).
- Due to fatty replacement and scar tissue as a result of muscle fibre degeneration.
- Gower’s sign (pushing up with the hands to get to the knees to stand).
204
inheritance of Duchenne Muscular Dystrophy
- X-lined disorder.
- 2/3 of boys affected inherit from their mother.
- 1/3 of boys affected occurs spontaneously (de novo).
205
course of Duchenne Muscular Dystrophy
- Condition progresses over time.
- Loss of ambulation occurs between the ages of 9 and 12 and
206
symptoms of Duchenne Muscular Dystrophy
- Speech delay
- Delayed walking.
- Clumsiness/falling.
- Progressive muscle weakness.
- Contractures.
- Scoliosis.
- Respiratory failure.
- Dysphagia.
- Cardiac failure.
207
speech and language presentation in Duchenne Muscular dystrophy
- Speech delay
- Language acquisition delay persisting through out childhood
- Short term verbal memory, phonological processing, cognitive delays
- ADHD/ASD 30%
- Deterioration oro-motor strength (later)
- Some- limited speech output
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swallowing presentation in Duchenne Muscular Dystrophy
- Dysphagia (70%) - likely under reported.
- Associated bulbar weakness.
- Intact lower cranial nerves.
- Tends to affects solids more than liquids.
- PEG feeding recommended after weight loss which cannot be remediated by dietetic means.
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prognosis of Duchenne Muscular Dystophy
death occurs in late 20s/early 30s
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prevalence of Duchenne Muscular Dystrophy
1/3500 - 1/5000 male births
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what is the milder version of Duchenne Muscular Dystrophy
Becker's muscular dystophy
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cause of Becker's muscular dystrophy
reduced dystrophin production in muscle fibres
dystrophin gene deletion of exons 48-51, this is an in-frame deletion meaning genetic code is somewhat retained allowing for some production of the protein
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prevalence of becker's muscular dystrohy
1/7000
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treatment of Duchenne muscular dystrophy
- steroids
- noninvasive stimulation
- ace inhibition
all of which improves life expectancy
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what does steriod treatment in duchenne muscular dystrophy do
- Delay loss of ambulation.
- Reduce rate of contracture formation.
- Reduce scoliosis formation.
- Stabilise cardiac and respiratory function.
- Prolong life expectancy.
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examples of steroids used for duchenne muscular dystrophy
prednisone & deflazacort
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dosage of prednisone for Duchenne Muscular Dystrophy
.75mg/kg/day
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dosage of deflazacort in duchenne muscular dystrophy
0.9mh/kg/day
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which congenital muscular dystrophy is prevalent in the Irish Traveller Population
LAMA2 (Merosin Negative Muscular Dystrophy)
