Hereditary motor and sensory neuropathy with proximal dominance

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Hereditary motor and sensory neuropathy with proximal dominance
Autosomal dominant inheritance
Synonyms Hereditary motor and sensory neuropathy, Okinawa type
Pronounce
Field Neurology
Symptoms Muscle weakness, involuntary contractions, asthenia, muscle atrophy, sensory loss, urinary incontinence, chronic cough
Complications Progressive motor disability, severe sensory loss
Onset Typically begins in the fourth decade of life (40s)
Duration Chronic and progressive
Types
Causes Mutation in the TFG gene (chromosome 3q13.2)
Risks Family history, genetic inheritance
Diagnosis Electromyography, nerve conduction study, genetic testing, muscle biopsy
Differential diagnosis Amyotrophic lateral sclerosis, other motor neuron diseases, Charcot–Marie–Tooth disease
Prevention None known
Treatment Supportive therapy, physical therapy, symptom management
Medication Muscle relaxants, antispasmodics, pain management
Prognosis Slowly progressive; variable severity
Frequency Rare; mostly identified in families from Okinawa, Japan and Brazil
Deaths Variable, typically due to complications in late-stage disease


Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P), also known as Hereditary motor and sensory neuropathy, Okinawa type, is a rare neurodegenerative disorder characterized by progressive muscle weakness, involuntary contractions, and loss of sensation. It is inherited in an autosomal dominant pattern and typically begins in the fourth decade of life.

Presentation[edit | edit source]

HMSN-P manifests with:

The disease has clinical overlap with amyotrophic lateral sclerosis (ALS), including similar neuropathological findings, such as TDP-43-positive cytoplasmic inclusions in motor neurons.

Genetics and Pathophysiology[edit | edit source]

HMSN-P is caused by mutations in the TFG (tropomyosin-receptor kinase fused gene) located on chromosome 3q13.2. The mutation affects intracellular protein trafficking and is believed to play a role in the degeneration of motor neurons through disruption of the ubiquitin-proteasome pathway.

Pathological findings include:

  • TFG/ubiquitin and/or TDP-43-positive cytoplasmic inclusions in spinal motor neurons
  • Cytosolic aggregation of TDP-43 in cultured cells expressing mutant TFG

Diagnosis[edit | edit source]

Diagnosis involves a combination of:

Treatment[edit | edit source]

There is no known cure for HMSN-P. Management is supportive and may include:

  • Physical therapy to maintain mobility
  • Assistive devices for ambulation
  • Medications to control spasticity or pain
  • Monitoring for urinary dysfunction

Prognosis[edit | edit source]

HMSN-P is slowly progressive. Disease severity and rate of progression vary among individuals. Although it is disabling, life expectancy may not be significantly reduced in all patients.

Epidemiology[edit | edit source]

HMSN-P is extremely rare. It has been described primarily in two large families from Okinawa, Japan. Cases have also been reported in descendants in Brazil, indicating a founder effect in these regions.

See also[edit | edit source]

External links[edit | edit source]



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Contributors: Prab R. Tumpati, MD