Genetic Causes and Management of Sensory Motor Neuropathy of Lower Limbs in Children

Primary Genetic Causes

CMT1A (PMP22 gene duplication) is the most prevalent form, accounting for approximately 70% of demyelinating CMT cases and 76-90% of sporadic CMT1 cases, according to the American Academy of Physical Medicine and Rehabilitation 1, 2
CMT1B is caused by point mutations in the myelin protein zero (MPZ) gene, accounting for about 5% of CMT cases, as reported by the American Academy of Physical Medicine and Rehabilitation 1, 2
CMT1D results from mutations in the early growth response 2 (EGR2) gene, occurring in approximately 2.5% of cases, according to the American Academy of Physical Medicine and Rehabilitation 1, 2
CMT2A is most commonly caused by MFN2 mutations, accounting for approximately 33% of axonal CMT cases, as reported by the American Academy of Physical Medicine and Rehabilitation 1, 2
CMTX is caused by mutations in the connexin32 (Cx32/GJB1) gene, accounting for approximately 12% of all CMT cases, according to the American Academy of Physical Medicine and Rehabilitation 1, 2

Sensory loss in a "glove and stocking" distribution is a common presentation, as noted by the European Society for Medical Oncology 3
Clinical evaluation should assess for distal muscle weakness, atrophy, and sensory deficits, as recommended by the American Academy of Pediatrics 4
Deep tendon reflexes should be evaluated, as suggested by the American Academy of Pediatrics 5
Electrophysiological studies can distinguish between demyelinating and axonal forms, according to the American Academy of Physical Medicine and Rehabilitation 1, 2

Physical therapy is recommended to maintain muscle strength and prevent contractures, as suggested by the European Society for Medical Oncology 3
Orthotic devices can be used for foot drop and stability, as recommended by the American Academy of Pediatrics 4
Pain management is essential for neuropathic pain, as noted by the European Academy of Neurology 6
Regular monitoring for progression of symptoms is crucial, as recommended by the European Society for Medical Oncology 3

Guillain-Barré syndrome should be considered in the differential diagnosis, as noted by the European Academy of Neurology 6, 8
Spinal cord tethering may present with sensorimotor disturbances of lower limbs, as reported by the American Academy of Pediatrics 4
Drug-induced peripheral neuropathy is a potential differential diagnosis, as noted by the European Hematology Association 7, 9

Genetic counseling should provide information on inheritance patterns specific to the identified genetic cause, as recommended by the American Academy of Physical Medicine and Rehabilitation 1, 2
Testing of asymptomatic family members should be considered when a pathogenic mutation is identified, as suggested by the American Academy of Physical Medicine and Rehabilitation 1