May 15, 2019

Spotlight on hereditary peripheral neuropathies

Peripheral neuropathy, or simply neuropathy, describes any condition that affects the normal activity of the network of nerves that form the peripheral nervous system. It is the peripheral nervous system that connects the brain and spinal cord to the rest of the body.

Neuropathy is commonly acquired as a result of trauma or a systemic disease such as diabetes, but there are a number of neuropathies that are genetic in origin. They may be inherited in an autosomal dominant, autosomal recessive or X-linked manor. They may also arise de novo.

Hereditary peripheral neuropathies are grouped into three categories: hereditary motor and sensory neuropathies, hereditary motor neuropathies and hereditary sensory and autonomic neuropathies.

Hereditary motor and sensory neuropathies

Hereditary motor and sensory neuropathies are also known as Charcot-Marie-Tooth disease, a group of disorders that affects both motor and sensory nerves. We discuss the genetic basis of Charcot-Marie-Tooth disease in detail in this earlier post.

Hereditary motor neuropathies

Hereditary motor neuropathies (HMNs), also known as distal hereditary motor neuropathies, are a group of disorders that share the common feature of selective involvement of the motor neurons with predominant effects on the distal limb muscles. This pattern is suggestive of a length-dependent mechanism that affects the longest motor neurons first.

Hereditary sensory and autonomic neuropathies

Hereditary sensory and autonomic neuropathies (HSANs) are a group of disorders that share the common feature of involving both sensory and autonomic neurons which typically results in symptoms of altered perception of temperature and/or pain and depressed reflexes (sensory) along with symptoms of autonomic disruption like excessive sweating, gastroesophageal reflux and/or postural hypotension.

Thorough examination of an individual’s medical and family history can help determine whether the neuropathy is likely due to an acquired or genetic cause. Physical examination and neurological testing, including nerve conduction velocity (NCV), electromyography (EMG) and nerve biopsy tests, provide insight into the clinical symptoms. The combination of apparent pattern of inheritance and clinical symptoms helps to differentiate between potential diagnoses. Genetic testing can further help to identify the molecular cause. Testing for Charcot-Marie-Tooth disease commonly focuses on PMP22 and the additional genes. Testing for hereditary motor neuropathies and hereditary sensory and autonomic neuropathies focus on a partially overlapping set of genes that continues to expand through further research.

WGS testing

With its ability to detect small sequence changes, large and small CNVs, tandem repeat expansions and mitochondrial variants across all genes, Variantyx’s Genomic Unity® test provides the most comprehensive genetic test available for identifying the underlying cause of an individual’s hereditary peripheral neuropathy.