Charcot-Marie-Tooth disease in Children

Neurology

Clinicals - History

Fact Explanation
Gait disturbances Usually these symptoms start as early as 2nd year of life but can be delayed till 5th decade.
The cause is due to demyelination and/or axonal loss of the peripheral nerves. As a result there is progressive weakness of the distal musculature particularly peroneal muscular atrophy which is accompanied by progressive weakness of dorsiflexion of the ankle and eventual foot drop. Pes cavus deformities invariably develop as well further destabilizing the gait , ,
Gait disturbances
Usually these symptoms start as early as 2nd year of life but can be delayed till 5th decade.
The cause is due to demyelination and/or axonal loss of the peripheral nerves. As a result there is progressive weakness of the distal musculature particularly peroneal muscular atrophy which is accompanied by progressive weakness of dorsiflexion of the ankle and eventual foot drop. Pes cavus deformities invariably develop as well further destabilizing the gait , ,
Proximal muscle weakness This is a late manifestation and axial muscles are usually spared. Proximal muscle weakness
This is a late manifestation and axial muscles are usually spared.
Tingling or burning sensations of the feet This is due to involvement of sensory nerves particularly large myelinated nerve fibers that convey proprioception and vibration but the threshold for pain and temperature can increase too. Tingling or burning sensations of the feet
This is due to involvement of sensory nerves particularly large myelinated nerve fibers that convey proprioception and vibration but the threshold for pain and temperature can increase too.
Easy traumatization Due to reduced muscle mass and sensory disturbance, the nerves are vulnerable to trauma and compression. Easy traumatization
Due to reduced muscle mass and sensory disturbance, the nerves are vulnerable to trauma and compression.
Blotching or pallor of the skin of the feet and inappropriately cold feet. Due to involvement of autonomic nerves and poor vasomotor control Blotching or pallor of the skin of the feet and inappropriately cold feet.
Due to involvement of autonomic nerves and poor vasomotor control
Auditory nerve deafness , This is due to a unique point mutation in PMP22 which causes progressive auditory nerve deafness in addition. , Auditory nerve deafness ,
This is due to a unique point mutation in PMP22 which causes progressive auditory nerve deafness in addition. ,

Clinicals - Examination

Fact Explanation
Wasted muscles in the anterior compartment of the lower legs and characteristic stork-like contour , Due to peroneal muscle atrophy , Wasted muscles in the anterior compartment of the lower legs and characteristic stork-like contour ,
Due to peroneal muscle atrophy ,
Weakness of dorsiflexion of the ankle and an ultimate foot drop , Due to peroneal muscle atrophy Weakness of dorsiflexion of the ankle and an ultimate foot drop ,
Due to peroneal muscle atrophy
Contractures of the wrists and ultimately a claw hand Due to wasting of forearm and hand muscles Contractures of the wrists and ultimately a claw hand
Due to wasting of forearm and hand muscles
Ankle contractures and painful Pes cavus deformities , Due to denervation of intrinsic foot muscles , Ankle contractures and painful Pes cavus deformities ,
Due to denervation of intrinsic foot muscles ,
Palpably enlarged nerves Due to hypertrophy of affected nerves due to demyelination followed by attempts of remyelination , Palpably enlarged nerves
Due to hypertrophy of affected nerves due to demyelination followed by attempts of remyelination ,
Lost tendon reflexes Due to demyelination and/or axonal loss of the peripheral nerves., Lost tendon reflexes
Due to demyelination and/or axonal loss of the peripheral nerves.,

Investigations - Diagnosis

Fact Explanation
Nerve conduction studies Motor and sensory nerve conduction velocities are very much reduced as slow as 20% of normal conduction time Nerve conduction studies
Motor and sensory nerve conduction velocities are very much reduced as slow as 20% of normal conduction time
Electromyography (EMG) Shows denervation and reinnervation Electromyography (EMG)
Shows denervation and reinnervation
Muscle biopsy Shows denervation and reinnervation Muscle biopsy
Shows denervation and reinnervation
Cerebrospinal fluid (CSF) for protein May be elevated, but no cells appear in the CSF. Cerebrospinal fluid (CSF) for protein
May be elevated, but no cells appear in the CSF.
Sural nerve biopsy Characteristic onion bulb formations of proliferated Schwann cell cytoplasm surround axons is seen and this pathologic finding is called interstitial hypertrophic neuropathy. In addition large- and medium-sized myelinated fibers are reduced in number, collagen is increased, and extensive segmental demyelination and remyelination also occur. Sural nerve biopsy
Characteristic onion bulb formations of proliferated Schwann cell cytoplasm surround axons is seen and this pathologic finding is called interstitial hypertrophic neuropathy. In addition large- and medium-sized myelinated fibers are reduced in number, collagen is increased, and extensive segmental demyelination and remyelination also occur.
Genetic analysis , , MT1A is predominantly caused by a 1.5 Mb duplication on chromosome 17p11.2 that includes the PMP22 gene. But due to the clinical and genetic heterogeneity, the low sensitivity of genetic testing for CMT2 and scarcity of clinical data, CMT can be difficult to be diagnosed by genetic testing always. , Genetic analysis , ,
MT1A is predominantly caused by a 1.5 Mb duplication on chromosome 17p11.2 that includes the PMP22 gene. But due to the clinical and genetic heterogeneity, the low sensitivity of genetic testing for CMT2 and scarcity of clinical data, CMT can be difficult to be diagnosed by genetic testing always. ,

Management - Supportive

Fact Explanation
Supportive care for the legs with stabilization of the ankles , This includes exercise training, shoe inlays, orthopaedic shoes and orthoses for stabilization of ankles , Supportive care for the legs with stabilization of the ankles ,
This includes exercise training, shoe inlays, orthopaedic shoes and orthoses for stabilization of ankles ,
Protection of the leg from compression neuropathies Placement of soft pillows beneath or between the lower legs Protection of the leg from compression neuropathies
Placement of soft pillows beneath or between the lower legs
Medical treatment with Phenytoin or Carbamezapine For burning paresthesias of the feet Medical treatment with Phenytoin or Carbamezapine
For burning paresthesias of the feet
Optimal control of blood sugar level Because co-existence of diabetes mellitus in a CMT1A patient can exacerbate symptoms of the peripheral neuropathy Optimal control of blood sugar level
Because co-existence of diabetes mellitus in a CMT1A patient can exacerbate symptoms of the peripheral neuropathy
Avoidance of certain neurotoxic agents Especially vincristine, can have a devastating effect, even in low dose therefore should be avoided Avoidance of certain neurotoxic agents
Especially vincristine, can have a devastating effect, even in low dose therefore should be avoided
Patient education and parental education Education regarding the course of the disease, prognosis and the extent of exercise capacity should be explained. Patients should be advised not to exercise to exhaustion, because of the risk of exercised-induced muscle damage. Patient education and parental education
Education regarding the course of the disease, prognosis and the extent of exercise capacity should be explained. Patients should be advised not to exercise to exhaustion, because of the risk of exercised-induced muscle damage.
Physiotherapy and occupational therapy Patients with CMT appeared to benefit significantly from a strengthening programme Physiotherapy and occupational therapy
Patients with CMT appeared to benefit significantly from a strengthening programme
Psychological support Group and family counseling may be beneficial and patients should be referred to support groups for psychological support and problem solving. If necessary, a patient should be referred to a mental health professional Psychological support
Group and family counseling may be beneficial and patients should be referred to support groups for psychological support and problem solving. If necessary, a patient should be referred to a mental health professional

Management - Specific

Fact Explanation
Surgical interventions Flexor Digitorum Superficialis Opposition tendon transfer has showed improved hand function, reduce disability, and improve quality of life
Surgical fusion of the ankle can also be done
Surgical interventions
Flexor Digitorum Superficialis Opposition tendon transfer has showed improved hand function, reduce disability, and improve quality of life
Surgical fusion of the ankle can also be done
Neurotrophin-3 (NT-3) Treatment with this led to slight improvement of sensory and reflex scores in CMT1A patients. NT-3 therapy resulted in measurable NT-3 secretion levels in blood and improvement in motor function, histopathology, and electrophysiology of the peripheral nerves Neurotrophin-3 (NT-3)
Treatment with this led to slight improvement of sensory and reflex scores in CMT1A patients. NT-3 therapy resulted in measurable NT-3 secretion levels in blood and improvement in motor function, histopathology, and electrophysiology of the peripheral nerves
Genetic counselling and antenatal diagnosis It maybe beneficial as these are autosomal dominant as well as could be recessive or X linked. Genetic counselling and antenatal diagnosis
It maybe beneficial as these are autosomal dominant as well as could be recessive or X linked.

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