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Key Features

  • Charcot-Marie-Tooth disease (HMSN type I, II)

    • Usually an autosomal dominant mode of inheritance

    • Occasional cases occur on a sporadic, recessive, or X-linked basis

  • Dejerine-Sottas disease (HMSN type III)

    • May occur on a sporadic, autosomal dominant or, less commonly, autosomal recessive basis

  • Friedreich ataxia

    • Only known autosomal recessive trinucleotide repeat disease

    • Caused by expansion of a poly-GAA locus in the gene for frataxin on chromosome 9, leading to symptoms in childhood or early adult life

  • Refsum disease (HMSN type IV)

    • Autosomal recessive disorder

    • Due to a disturbance in phytanic acid metabolism

  • Porphyria

    • Peripheral nerve involvement may occur during acute attacks in both variegate porphyria and acute intermittent porphyria

Clinical Findings

  • Charcot-Marie-Tooth disease (HMSN type I, II)

    • Foot deformities or gait disturbances in childhood or early adult life

    • Slow progression leads to typical features of polyneuropathy

      • Distal weakness and wasting that begin in the legs

      • A variable amount of distal sensory loss

      • Depressed or absent tendon reflexes

    • Tremor is a conspicuous feature in some instances

  • Dejerine-Sottas disease (HMSN type III)

    • Onset in infancy or childhood

    • Progressive motor and sensory polyneuropathy with weakness, ataxia, sensory loss, and depressed or absent tendon reflexes

    • Peripheral nerves may be palpably enlarged and are characterized pathologically by segmental demyelination, Schwann cell hyperplasia, and thin myelin sheaths

  • Friedreich ataxia

    • Gait becomes ataxic

    • Hands become clumsy

    • Other signs of cerebellar dysfunction develop accompanied by weakness of the legs and extensor plantar responses

    • Involvement of peripheral sensory fibers leads to sensory disturbances in the limbs and depressed tendon reflexes

    • Bilateral pes cavus

  • Refsum disease (HMSN type IV)

    • Pigmentary retinal degeneration is accompanied by progressive sensorimotor polyneuropathy and cerebellar signs

    • Auditory dysfunction, cardiomyopathy, and cutaneous manifestations may also occur

  • Porphyria

    • Motor symptoms usually occur first

    • Weakness is often most marked proximally and in the upper limbs rather than the lower

    • Sensory symptoms and signs may be proximal or distal in distribution

    • Autonomic involvement is sometimes pronounced

Diagnosis

  • Nerve conduction velocity and electromyography studies

  • Sural nerve and/or muscle biopsy

    • Charcot-Marie-Tooth disease (HMSN type I, II)

      • In HMSN type I

        • Reduction in motor and sensory conduction velocity is marked

      • In HMSN type II

        • Motor conduction velocity is normal or only slightly reduced

        • Sensory nerve action potentials may be absent

        • Signs of chronic partial denervation are found in affected muscles

        • Predominant pathologic change is axonal loss rather than segmental demyelination

      • Dejerine-Sottas disease (HMSN type III)

        • Conduction is slowed

        • Sensory action potentials may be unrecordable

      • Friedreich ataxia

        • Marked loss of cells in the posterior root ganglia and degeneration of peripheral sensory fibers

        • Changes are conspicuous in the posterior and lateral columns of the spinal cord

        • Conduction velocity in motor fibers is normal or only mildly reduced

        • Sensory action potentials are small or absent

      • Refsum disease (HMSN type IV)

        • Motor and sensory conduction velocities are reduced, often markedly

        • There may be electromyographic evidence of denervation in affected muscles

      • Porphyria

        • Electrophysiologic findings are in ...

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