L3.2 Neuromuscular Diseases Part 2 Flashcards by Naomi Nakazato

group of inherited, primary diseases of muscle characterized by progressive loss of strength in specific muscle groups.

Muscular dystrophies

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The most common form of muscular dystrophy

Duchenne muscular dystrophy

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Duchenne muscular dystrophy is recessive/dominant sex-linked gene located on the chromosome ___ and carried only by males/females.

recessive, X, females

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Duchenne muscular dystrophy is also known as

pseudohypertrophic muscular dystrophy

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Progressive disease in which the child becomes weaker and usually dies of a respiratory infection or cardiorespiratory insufficiency in the late teen or early 20s

Duchenne muscular dystrophy

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T/F.
Most frequent presenting symptom of DMD is

Abnormal gait
Frequent falls
Difficulty climbing steps

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Gait pattern of DMD :
toe walking with compensatory adaptation to weak knee flexor/extensor and lordotic posture of spine as a compensation to hip flexor/extensor weakness

knee extensor, hip extensor

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____ is the deficiency at the plasma membrane of muscle & disrupts membrane cytoskeleton and leads to secondary loss of other components of muscle cytoskeleton

dystrophin

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dystrophin
1. causes membrane instability leading to membrane injury
2. Causes aggressive fibrotic replacement of muscle and eventually there is failure of regeneration with muscle fiber death and loss

T,F
F,T
both T
both F

both T

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_____ is required inside muscle cells for structural support & strengthen muscle cells by anchoring elements of the internal cytoskeleton to the surface membrane.

dystrophin

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Absence of dystrophin leads to disruption of linkages in cytoskeleton of cell membrane. This leads to

a. membrane microtears
b. Increase calcium channel leaks
c. necrosis of cell
d. all

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Without _____, the cell membrane becomes permeable, so that extracellular components enter the cell, increasing the internal pressure until the muscle cell “explodes” and dies. The subsequent immune response can add to the damage.

dystrophin

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T/F. DMD onset is noted before 5 years

F, 4 yrs.

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Apparent enlargement of calf and sometimes other muscles which is due to an accumulation of fat and connective tissue in the muscle

Pseudohypertrophy

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T/F. Enlarged tongue (macroglossia) causes wide arch to mandible and maxilla with separation of teeth

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T/F. Mild mental retardation has been noted in some boys with Duchenne dystrophy

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Cardiac abnormalities – dystrophic protein is present in both myocardium and cardiac Purkinje fiber
Nearly all patient over 12 demonstrates abnormalities in ECG

T,F
F,T
both T
both F

T, F (over 13)

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Respiratory difficulties of DMD are due to:

a. Weakness of respiratory muscles

b. Alteration in respiratory system mechanics

c. Impairment of central control of respiration

d. All

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Breathing becomes affected during the earlier stages of Duchenne, leading to respiratory infections
Severe respiratory and heart problems mark the disease’s final stages, usually in the boy’s teens and early 20s

T,F
F,T
both T
both F

F (later stages), T

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Diagnosis for DMD includes:

a. Family history

b. History of malignant hyperthermia during general anesthesia for an unrelated surgical intervention

c. Elevated CK

d. all

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Complications of DMD include:

a. Contractures
b. Scoliosis
c. Respiratory tract infection
d. Bed sores
e. All

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DMD functional grades of UE.
what grade is:
Standing with arms at the sides, patient can abduct the arm in a full circle until they touch above the head

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DMD functional grades of UE.
what grade is:
Patient cannot raise hands above the head, but can raise an 8 oz glass of water to the mouth (using both hands if necessary)

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DMD functional grades of UE.
what grade is:
Patient can raise arm above head by flexing the elbow or using accessory muscles

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DMD functional grades of UE. what grade is: Patient can raise hands to the mouth but cannot raise an 8 oz glass of water to the mouth

DMD functional grades of UE. what grade is: Patient cannot raise hands to the mouth and has no useful function of hands

DMD functional grades of UE. what grade is: Patient cannot raise hands to the mouth but can use the hands to hold a pen or pick up pennies from a table

DMD functional grades of LE. what grade is: Walks and climbs stairs without assistance

DMD functional grades of LE. what grade is: Walks and climbs stairs slowly (elapsed time of more than 12 seconds for four standard stairs) with aid of a railing

DMD functional grades of LE. what grade is: Walks and climbs stairs with the aid of a railing

DMD functional grades of LE. what grade is: Walks unassisted and rises from a chair, but cannot climb stairs

DMD functional grades of LE. what grade is: Walks unassisted but cannot rise from a chair or climb stairs

DMD functional grades of LE. what grade is: Walks only with assistance or walks independently with long leg braces

DMD functional grades of LE. what grade is: Is in a wheelchair

DMD functional grades of LE. what grade is: Is confined to bed

DMD functional grades of LE. what grade is: stand in long leg braces, but is unable to walk even with assistance

DMD functional grades of LE. what grade is: Walks in long leg braces, but requires assistance for balance

What is the treatment of DMD a. No pharmaceutical treatment b. Glucocorticoid corticosteroids c. Creatine monohydrate d. Myoblast transplant

Given between 6 months to 2 years have improved function; kept those affected “stronger for longer” a. No pharmaceutical treatment b. Glucocorticoid corticosteroids c. Creatine monohydrate d. Myoblast transplant

Glucocorticoid corticosteroids

(natural occurring substance used by body builders) increased muscle performance a. No pharmaceutical treatment b. Glucocorticoid corticosteroids c. Creatine monohydrate d. Myoblast transplant

Creatine monohydrate

aim to replace missing dytrophin a. No pharmaceutical treatment b. Glucocorticoid corticosteroids c. Creatine monohydrate d. Myoblast transplant

____ is similar to the Duchenne form, but appears somewhat later in life and progresses more slowly.

Becker's muscular dystrophy

Patients with Becker dystrophy had defects in the same dystrophin gene chromosome ____

____ can first appear later than Duchene

Becker’s dystrophy

Progression is typically slow and walk usually preserved into the 30s (some up to late 40s and 50s ) a. DMD b.Becker’s dystrophy

Becker’s dystrophy

T/F. Becker patients have longer life expectancy than Duchenne

CPK may be elevated * Gradual proximal weakness (LE initially with gradual involvement of pectoral and UE at 10 – 20 years from onset) * Extensors are weaker than flexor a. DMD b.Becker’s dystrophy

Becker’s dystrophy

Muscle noted to be most severely involved in Becker’s dystrophy: a. hip extensor b. knee extensors c. neck flexors d. all

Age of onset 4 years old Progressive is fast, loss of ambulatory function by 10 Gene location Xp21 Almost absent dysrophin Presence of mental retardation a. DMD b.Becker’s dystrophy

Age of onset between 5 to 15 years Slower rate of progression, ability to walk even up to late teen Gene location Xp21 Abundance of dystrophin in immunostaining Mental retardation not common; mildly reduced intellectual performance but degree of impairment is not as severe as DMD a. DMD b.Becker’s dystrophy

Cardiac problem is usually severe Respiratory problem is seen as early as 5 to 10 years old Contractures develop early scoliosis is more common and usually severe Gower’s and pseudohypertrophy common a. DMD b.Becker’s dystrophy

Cardiac involvement is mild and slowly progressive Lesser pulmonary dysfunction Early development of contracture is not common Scoliosis is not common and severe Gower’s and calf enlargement is a nonspecific finding a. DMD b.Becker’s dystrophy

Age of onset 3 – 12 years old Sex Male and female Distribution and pattern of weakness Proximal muscles; slower rate of progression Pathology Abnormality in dystrophin associated glycoprotein Signs and symptoms Calf hypertrophy, + Gower’s, loss of ambulation between 10- 20 years old, Spinal deformity less problematic than DMD, restrictive pulmonary insufficiency not as severe as DMD, fewer cardiac manifestation a. DMD b.Becker’s dystrophy c. Severe Childhood Autosomal Recessive Muscular Dystrophy (SCARMD)

Group of infants presenting with hypotonia, muscle weakness at birth or within first few months of life, congenital contracture and dystrophic pattern on muscle biopsy a. DMD b.Becker’s dystrophy c. Severe Childhood Autosomal Recessive Muscular Dystrophy (SCARMD) d. Congenital Muscular Dystrophy

Usually static but some may show slow progression while others gain developmental milestones and achieve ability to walk a. DMD b.Becker’s dystrophy c. Severe Childhood Autosomal Recessive Muscular Dystrophy (SCARMD) d. Congenital Muscular Dystrophy

mental retardation, structural malformation, dystrophic myopathy a. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Fakuyama congential muscular dystrophy) b. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Walker Warburg syndrome) c. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (muscle eye-brain disease) d. CONGENITAL MUSCULAR DYSTROPHY WITHOUT CENTRAL NERVOUS SYSTEM INVOLVEMENT

mental retardation, ocular abnormality, cleft lip /palate a. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Fakuyama congential muscular dystrophy) b. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Walker Warburg syndrome) c. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (muscle eye-brain disease) d. CONGENITAL MUSCULAR DYSTROPHY WITHOUT CENTRAL NERVOUS SYSTEM INVOLVEMENT

weakness, retardation, ocular abnormality (myopia and uncontrolled eye movement) a. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Fakuyama congential muscular dystrophy) b. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Walker Warburg syndrome) c. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (muscle eye-brain disease) d. CONGENITAL MUSCULAR DYSTROPHY WITHOUT CENTRAL NERVOUS SYSTEM INVOLVEMENT

Main features are muscle weakness, hypotonia, congenital contracture, normal to moderately elevated CK, normal intellect a. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Fakuyama congential muscular dystrophy) b. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (Walker Warburg syndrome) c. Congenital muscular dystrophy with CENTRAL NERVOUS SYSTEM INVOLVEMENT (muscle eye-brain disease) d. CONGENITAL MUSCULAR DYSTROPHY WITHOUT CENTRAL NERVOUS SYSTEM INVOLVEMENT

Physical therapy intervention for congenital myopathy: a. Maintenance of flexibility with stretching and appropriate bracing or casting b. Bracing is needed for standing or ambulation c. Power mobility should be considered for those with sufficient cognitive skills d. all

Age of Onset Teens or early adulthood Inheritance/ gender affected: Autosomal dominant/ males and females Muscles first affected Face, shoulder girdle muscles Progression Slow, sometimes with rapid spurts a. DMD b.Becker’s dystrophy c. Severe Childhood Autosomal Recessive Muscular Dystrophy (SCARMD) d. Fascioscapulohumeral Muscular dystrophy

third most common muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD)

T/F. Facial weakness of FSHD involves: orbicularis oculi, zygomaticus and orbicularis oris; with expressionless appearance, difficulty in whistling, pursing lips, drinking through straw or smiling

FSHD Spares what muscles a. masseter b. temporalis c. extraocular muscle d. pharyngeal muscle e. all

1. UE involvement of FSHD includes: trapezius, rhomboids, serratus anterior, latissium dorsi 2. * Scapula positioned anteriorly give the shoulder a forward sloped appearance T,F F,T both T both F

T, F (laterally)

T/F. The weakness of FSHD can spread to the muscles of abdomen, feet, upper arms, pelvic area and lower arms

* Early onset FSHMD with sensory neural hearing deficit * Presents with myopathy in infancy and progresses fairly rapidly * Become wheelchair reliant by late 2 nd and 3 rd decade a. DMD b.Becker’s dystrophy c. Severe Childhood Autosomal Recessive Muscular Dystrophy (SCARMD) d. Coat's syndrome

Other related problems of FSHMD, EXCEPT: a. Spinal deformity as scoliosis and hyperlordosis b. Mild restrictive lung disease c. Cardiac problems are uncommon d. Contractures are relatively rare e. C & D

E. (Cardiac problems are rare. Contractures are relatively uncommon)

The mutation associated with FSHD is located on human chromosome ___

Age of onset some seen in early childhood, other Adolescence or early adulthood Inheritance/ gender X-linked recessive/male Muscles first affected Upper arms, lower legs *contracture of elbow flexor hallmark of EMD Progression slow a. DMD b.Becker’s dystrophy c. Severe Childhood Autosomal Recessive Muscular Dystrophy (SCARMD) d. Coat's syndrome e. Emery Dreifuss Muscular Dystrophy

All are true about Emery Dreifuss Muscular Dystrophy, EXCEPT: a. A rare form of muscular dystrophy b. Weakness generally starts in the shoulders, upper arms and lower legs (scapulohumeral and peroneal distribution) c. Weakness my spreads to involve the muscles of chest and pelvic area d. Life threatening heart problems (as cardiomyopathy, arrhythmia) are uncommon e. May show evidence of nocturnal hypoventialation due toestrictive expansion of chest

d. [Life threatening heart problems (as cardiomyopathy,arrhythmia) are COMMON]

Emery Dreifuss Muscular Dystrophy: 1. Has tight cervical and lumbar spinal extensor muscle resulting in limitation of neck and trunk flexion; unable to flex chin to sternum or touch toes 2. Is caused by a defect in the gene on the X chromosome X that codes for the protein called emerin T,F F,T both T both F

both T

Age of onset: early childhood (2-6) X- link, Xp21 Lack of dystrophin Toe walk is due to compensatory strategy to stabilize knee because of proximal weakness Proximal muscles LE> UE Life expectancy: rarely beyond 20s a. DMD b. Emery Dreifuss Muscular Dystrophy

Age of onset: early childhood or adolescence or early adulthood X-link, Xq28 Lack of emerin Toe walk is due to weakness of dorsiflexors Selective scapulohumeral peroneal distribution weakness by sparing deltoid and forearm muscle Life expectancy: variable a. DMD b. Emery Dreifuss Muscular Dystrophy

Age of onset Childhood and adulthood Inheritance/gender Autosomal recessive and dominant forms/ male and female Muscles first affected Proximal shoulder and pelvic girdle muscles progression Usually slow a. DMD b. Emery Dreifuss Muscular Dystrophy c. Limb girdle muscular dystrophy

Limb girdle muscular dystrophy . 1. The limb-girdle form of the disease first affects the muscles of the hip and shoulder areas. 2. There are several forms that vary from mode of inheritance, chromosome affected, clinical presentation T,F F,T both T both F

both T

Term applied to muscle disorders presenting in infancy with generalized muscle weakness and hypotonia followed by delayed developmental milestones

congenital myopathy

all are definitions of Congenital myopathy, EXCEPT: a. First described in 1956 , central core disease b. May be differentiated diagnostically through morphologic characteristics using electron microscope, enzyme histochemistry, immunocytochemistry, molecular analysis c. Mode of inheritance and gene loci are variable d. None

T/F. Features of congenital myopathy are Onset: early life presenting with hypotonia, hyporeflexia, generalized weakness (proximal than distal) Poor muscle bulk Dysmorphic feature Non progressive Hereditary Morphologic features in histochemical exam of muscle biopsy

T/F. Clinical signs of a floppy infant Frog leg posture Reduced movement with legs fully abducted and arms lying beside the body either flexed or extended Head lag Round back when sitting Rag doll posture

T/F. Laboratory findings of congenital myopathy are Creatinine kinase Normal or mild elevation EMG and NCV NCV studies normal EMG normal ______________ – Gold standard See ultra structure of muscle Genetic studies are required for diagnosis

F (not required) Muscle biopsy – Gold standard

all are definitions of Congenital myopathies, EXCEPT: a. Heterogenous disorders presenting with infantile hypotonia due to genetic defects causing myopathies with the absence of any structural abnormality of the CNS or peripheral nervous system b. Develop symmetrical proximal weakness predominantly limb girdle distribution c. Non-progressive and static d. None

Congenital myopathies have: 1. CPK normal, EMG normal or may have mild, nonspecific changes of myopathic character 2. Patients do not lose muscle fibers as in the case of dystrophic myopathies T,F F,T both T both F

both T

Congenital myopathies with: absent mitochondria and sarcoplasmic reticulum in the core region Autosomal dominant affecting chromosome 19; present with mild, nonprogressive proximal or generalized weakness but achieves motor milestones rather late; related with + history of malignant hyperthermia a. Central cord b. Nemaline or “rod body myopathy”

Congenital myopathies with: Typical form is autosomal recessive * some autosommal dominant with locus at chromosome 1; mild nonprogressive myopathy with hypotonia and proximal weakness; may have kyphoscoliosis, cardiomyopathy, pigeon chest, pes cavus, swallowing problems -severe form may present in neonates with respiratory difficulty; fatal a. Central cord b. Nemaline or “rod body myopathy”

X-link recessive chromosome X; presents with severe respiratory insufficiency, generalized hypotonia, swallowing difficulty, congenital contractures, facial weakness and weakness of extraocular muscles a. Central cord b. Nemaline or “rod body myopathy” c. Severe X-link myotubular myopathy d. Mini-core Disease

Autosommal recessive Due to decrease in mitochondrial oxidative enzymes in some muscles; presents with hypotonia and delayed motor development, mild facial weakness and diaphragmatic weakness putting them at risk for nocturnal hypoventilation a. Central cord b. Nemaline or “rod body myopathy” c. Severe X-link myotubular myopathy d. Mini-core Disease

Autosomal recessive and dominant pattern; type 1 fibers smaller than type 2 Presents with infantile hypotonia, delayed gross motor milestones, non progressive with kyphoscoliosis, long narrow face, high arch palate, high arch a. Congenital fiber type disproportion b. Nemaline or “rod body myopathy” c. Severe X-link myotubular myopathy d. Mini-core Disease

Non-X linked; presents with early hypotonia, delayed motor milestone, genralized weakness of both proximal and distal, ptosis, weakness of external ocular muscles and axial muscle Autosomal dominant inheritance a. Congenital fiber type disproportion b. Myotubular myopathy (Centronuclear myopathy) c. Severe X-link myotubular myopathy d. Mini-core Disease

Example Central core Etiology Congenital, Metabolic, Endocrine inheritance Sporadic, Autosomal recessive Progression Static or improves with time or treatment Muscle enzyme Mildly increased or normal EMG No fibrillation a. myopathy b. dystrophy

Example Duchene Becker’s Limb girdle Etiology genetic Inheritance Always inherited Progression Always progressive Muscle enzyme Markedly increased EMG Fibrillation present a. myopathy b. dystrophy

a state of delayed relaxation or sustained contraction of skeletal muscle

myotonia

Age of onset Early childhood to adulthood; newborn period for congenital form Inheritance/ gender affected Autosomal dominant/ males and females Muscles first affected Face, feet, hands, front of neck Progression slow a. DMD b.Becker’s dystrophy c. Myotonic muscular dystrophy

All are definition of Myotonic muscular dystrophy, EXCEPT: * Also known as _____ a. Affects skeletal muscle, smooth, myocardium, brain and ocular structures b. Associated findings is baldness and gonadal atrophy (males), cataracts and cardiac dysrrhythmias c. Most common adult form of myotonic muscular dystrophy d. Presents with an unusual symptom, myotonia, which is similar to spasm or stiffening of muscles. e. None

E, Steinert’s disease

Myotonic muscular dystrophy is autosomally dominant/recessive disease affecting both sexes. 1. It is characterized by an inability of the muscles to relax 2. primarily affects the muscles of the hands and feet T,F F,T both T both F

dominant , both T

T/F. Facial features of Myotonic muscular dystrophy is: long, thin face with temporal and masseter muscle wasting, “lugubrious facie” Males have frontal baldness

True about Myotonic muscular dystrophy, EXCEPT: a. Greater involvement of the distal than proximal muscles b. Patients with Myotonic Muscular Dystrophy seen to require more sleep c. They have mild mental retardation d. Cardiac problems can be serious and should be followed up carefully e. None

True about Myotonia Congenita or Thomsen’s disease, EXCEPT: Autosomal dominant/recessive? a. Present at birth but manifest late like difficulty releasing object or difficulty walking b. Exacerbated by prolong rest or inactivity and aggravated by cold c. Muscle hypertrophy or “Herculean” appearance d. Recessive form (called Becker form) is late onset with more myotonia , hypertrophy with weakness e. None

dominant, E

True about Paramyotonia Congenita: a. Autosomal dominant b. Mild involvement, usually aggravated by cold c. + hypertrophy of musculature with severe hand and facial involvement but myotonic episodes subside within hours d. All

True about Schwartz Jampel syndrome: a. Autosomal recessive b. Dwarfism, diffuse bone disease, narrow palpebral fissure, blepharospasm, micrognathia and flat facies c. Skeletal abnormalities: short neck, kyphosis, hypertrophic muscles which are stiff d. all

NMJ Disorders. Born to mothers with MG due to transplacental transfer; symptoms present within first few hours; with difficulty feeding, generalized weakness, respiratory problems, weak cry, facial weakness, sometimes ptosis; resolves within 2-3 weeks a. Transient Neonatal Myasthenia b. Congenital Myasthenia Syndromes c. Autoimmune Myasthenia Gravis d. Infantile Botulism e. Acquired Botulism

Genetic disorder may present during neonatal period, late childhood or adult life; initial presentation is ptosis, ophthalmoparesis, facial weakness, generalized hypotonia a. Transient Neonatal Myasthenia b. Congenital Myasthenia Syndromes c. Autoimmune Myasthenia Gravis d. Infantile Botulism e. Acquired Botulism

Onset is insidious presenting with acute respiratory difficulties, ptosis, ophthalmoparesis, facial weakness, swallowing difficulties, weakness or trunk, limbs (proximal>distal) usually at the end of the day a. Transient Neonatal Myasthenia b. Congenital Myasthenia Syndromes c. Autoimmune Myasthenia Gravis d. Infantile Botulism e. Acquired Botulism

Happens between 10 days to 6 months, acute onset of hypotonia, dysphagia, constipation, weak cry, respiratory insufficiency, hypotonia, ptosis, weakness; diagnosis: (+) Clostridium botulinum toxin in rectal aspirate a. Transient Neonatal Myasthenia b. Congenital Myasthenia Syndromes c. Autoimmune Myasthenia Gravis d. Infantile Botulism e. Acquired Botulism

Acquire form poorly cooked contaminated food with toxin or from open wound that comes in contact with the bacteria through soil; presents with ptosis, diplopia, bulbar weakness, constipation, pupillary dilation a. Transient Neonatal Myasthenia b. Congenital Myasthenia Syndromes c. Autoimmune Myasthenia Gravis d. Infantile Botulism e. Acquired Botulism