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Detailed information of CENTRONUCLEAR MYOPATHY
CENTRONUCLEAR MYOPATHY
DEFINITION:
A congenital myopathy characterized by generalized hypotonia,
muscle weakness, and central nuclei on muscle biopsy.
EPIDEMIOLOGY:
- incidence: ?
- age of onset:
- newborn (AR type); 1st to 3rd decades (AD type)
- risk factors:
- familial - autosomal recessive (AR)
- autosomal dominant (AD)
- chrom.#: ?
- gene: ?
- M < F (1:1.5) AR type; M > F (2:1) AD type
- Blacks > Whites (AR form)
PATHOGENESIS:
- vimentin and desmin are filamentous proteins which act
as cyto-skeletal elememts in developing fetal myotubes and
serve to attach nuclei and mitochondria to the sarcolemma
and preserve their central position
- as fetal myotubes mature, vimentin and desmin decrease
in amount and the nuclei and mitochondria are redistributed
- by term the vimentin in muscle cells has disappeared and
desmin remains in trace amounts
- synthesis of vimentin and desmin is controlled by
chromosomal areas 10p13 and 2q35, respectively
2. Genetic Defect
- genetic defect -> ? persistence of vimentin and desmin
-> matur-ational arrest of fetal muscle at myotubular stage
(8-15 weeks gestational age) -> central nuclei and
mitochondria -> clinical manifestations
PATHOLOGY:
- all muscles affected and 50-90% of fibres within a
biopsy will be abnormal
- central nuclei
- lie in a core of cytoplasm surrounded by a cylinder of
contractile myofibrils (nuclei surrounded by a clear halo)
- arranged in rows with the spaces between the nuclei
filled with mitochondria
- stains
- vimentin and desmin detected by immunohistochemistry
- central distribution of stains for glycolysis and
oxidative phosphorylation
- mature ATPase stain for cylinder of myofibrils
- central cores are devoid of ATPase
- structured - myofibrils are normal in arrangement
- unstructured - " randomly arranged
- others
- type 1 fibres are predominantly affected and are
smaller (atrophied)
- type 2 fibres appear to be spared
- on EM, clusters of mitochondria, lipopigments,
glycogen, autophagic vacuoles, rER, and Golgi complexes
are observed in the perinuclear central zone
CLINICAL FEATURES:
- generalized infantile hypotonia and diffuse muscle
weakness
- proxmial > distal muscle groups
- gross motor developmental delay
- with slow progression so that confined to a
wheel-chair by adolescence or early adulthood
- respiratory muscles -> respiratory distress
- facial muscles -> myopathic facies, weak cry, suck,
nasal speech, inability to bury eyes
- ocular muscles -> ptosis, strabismus,
ophthalmoplegia
- sternocleidomastoid muscle -> weak neck flexion
- deep tendon reflexes absent or depressed
- normal intelligence
- seizures (in 18% of cases)
2. Musculoskeletal Manifestations
- dolichocephalic head, high-arched palate
2. Skeletal
- pectus excavatum
- short stature
- slowly progressive lordosis, scoliosis, winging of
scapula
- talipes equinovarus
2. Autosomal Dominant Type
- diffuse muscle weakness
- limb-girdle distribution and slowly progressive so
patient eventually confined to a wheelchair
INVESTIGATIONS:
- normal or slightly elevated CPK
2. EMG
- myopathic - brief, small amplitude, polyphasic motor
potentials
3. Nerve Conduction Studies
- usually normal but sometimes slow
MANAGEMENT:
- multidisciplinary approach
- Paediatrics - promote ambulation and physiotherapy,
moniter deformities
- Surgery - moniter and correct deformities
- Genetics - genetic counselling, prenatal diagnosis
2. Prognosis
- Autosomal Recessive Type - fair
- Autosomal Dominant Type - good
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