71 Hereditary Polyneuropathies
The hereditary motor and sensory neuropathies (HMSNs) account for approximately 40% of chronic neuropathies. There are now more than 40 known genes or loci for the various forms of HMSN, which are collectively known as Charcot–Marie–Tooth disease (CMT). About 1 in 2500 persons is affected by CMT. New genes or loci for CMT subtypes are identified very frequently. Less common inherited polyneuropathies are those associated with systemic genetic disorders and inborn errors of metabolism (Table 71-1). Advances in genetic characterization of the inherited neuropathies have afforded greater insight into their biologic basis, and there is increasing interest in therapeutic strategies for these disorders, which can cause lifelong morbidity related to weakness, sensory loss, and orthopedic complications.
Table 71-1 Classification of Inherited Polyneuropathies
| Inheritance | Neurophysiology | |
|---|---|---|
| Hereditary motor and sensory neuropathy type 1 | Autosomal dominant | Demyelinating |
| Hereditary motor and sensory neuropathy type 2 | Autosomal dominant Autosomal recessive |
Axonal |
| Hereditary motor and sensory neuropathy type 3 | Autosomal/de novo dominant | Demyelinating |
| Hereditary motor and sensory neuropathy type 4 | Autosomal recessive | Demyelinating |
| Intermediate CMT | Autosomal dominant | Mixed |
| X-linked CMT | X-linked dominant, X-linked recessive |
Mixed |
| Hereditary sensory and autonomic neuropathies | Autosomal recessive | Axonal |
| Hereditary motor neuropathies | Autosomal dominant | Axonal |
| Hereditary neuropathy with liability to pressure palsies | Autosomal dominant | Demyelinating |
| Other Inherited Neuropathies | ||
| Hereditary neuralgic amyotrophy | Autosomal dominant | Axonal |
| Familial amyloid polyneuropathy | Autosomal dominant | Axonal |
| Giant axonal neuropathy | Autosomal recessive | Axonal |
| Infantile neuroaxonal dystrophy | Autosomal recessive | Axonal |
| Andermann syndrome | Autosomal recessive | Axonal |
| Neuropathies Associated with Inborn Errors of Metabolism | ||
| Lipid Disorders | ||
| Cerebrotendinous xanthomatosis | Autosomal recessive | Mixed |
| Abetalipoproteinemia, hypolipoproteinemia | Autosomal recessive | Demyelinating |
| Ataxia with vitamin E deficiency | Autosomal recessive | Demyelinating |
| Peroxisomal Disorders | ||
| Refsum disease | Autosomal recessive | Demyelinating |
| Adrenomyeloneuropathy | X-linked | Axonal |
| Mitochondrial Cytopathies | ||
| NARP | Autosomal recessive | Mixed |
| MNGIE | Autosomal recessive | Mixed |
| Leigh disease | Autosomal recessive | Mixed |
| Lysosomal Enzyme Diseases | ||
| Globoid cell leukodystrophy | Autosomal recessive | Demyelinating |
| Metachromatic leukodystrophy | Autosomal recessive | Demyelinating |
| Fabry disease | X-linked | Axonal |
| Tyrosinemia type 1 | Autosomal recessive | Axonal |
| Sphingomyelin Lipidoses | ||
| Niemann–Pick disease type C | Autosomal recessive | Demyelinating |
| Farber disease | Autosomal recessive | Demyelinating |
| Porphyrias | ||
| Acute intermittent porphyria | Autosomal dominant | Axonal |
| Hereditary coproporphyria | Autosomal dominant | Axonal |
| Variegate porphyria | Autosomal dominant | Axonal |
| Disorders with Defective DNA Synthesis or Repair | ||
| Ataxia telangiectasia | Autosomal recessive | Axonal |
