On this page
Hereditary motor neuropathy (distal, dominant)
This condition impacts the motor neurons, which are nerve cells responsible for voluntary movement. It typically causes progressive weakness and muscle loss, initially in the extremities, and is passed down through families in an autosomal dominant pattern.
Overview
Hereditary motor neuropathy (HMN) refers to a group of genetic conditions characterised by progressive weakness and wasting of muscles, primarily due to the degeneration of motor nerves. Unlike some other neuropathies, HMN generally affects motor nerves while largely sparing sensory nerves, meaning that sensations like touch and pain are typically preserved. The term 'distal' indicates that the symptoms usually begin in the parts of the body furthest from the centre, such as the hands and feet [PMID:27389230]. 'Dominant' describes the inheritance pattern, meaning only one copy of an altered gene is needed for the condition to develop. HMN is a rare disorder, and its exact prevalence is not well established.
Symptoms & clinical features
The symptoms of hereditary motor neuropathy (distal, dominant) typically involve progressive muscle weakness and atrophy (wasting) in the extremities. Early signs often include difficulty with fine motor skills in the hands, such as buttoning clothes or writing, and foot drop, which can lead to stumbling or an altered gait. Muscle cramps and fasciculations (small, involuntary muscle twitching) may also be experienced [PMID:27389230]. As the condition progresses, weakness can spread from the feet to the lower legs, and from the hands to the forearms, though the proximal (closer to the body's centre) muscles are often less affected. The severity and rate of progression can vary significantly among individuals, even within the same family.
Video: Genetics 101
Affected organs
Hereditary motor neuropathy predominantly affects the peripheral nervous system, specifically the motor neurons. These nerve cells originate in the spinal cord and extend to the muscles, carrying signals that control voluntary movement. The degeneration of these motor neurons leads to the muscles they supply becoming weak and wasting away. While sensory nerves are generally spared, the primary impact is on the muscles of the hands, feet, lower legs, and forearms.
Risks & severity
The severity of hereditary motor neuropathy (distal, dominant) can range from mild forms with minimal impact on daily life to more severe presentations that significantly affect mobility and function. The age of onset is also variable, often appearing in childhood or adolescence, but can sometimes emerge in adulthood. The condition is typically progressive, meaning symptoms tend to worsen over time, though the rate of progression differs between individuals and specific genetic causes. While the condition primarily impacts physical movement, it is generally not considered life-threatening.
Genetic causes
Hereditary motor neuropathy (distal, dominant) is caused by pathogenic variants in several genes. Key genes associated with this condition include GARS1, HSPB1, and HSPB8 [PMID:33671228]. The proteins produced by these genes play important roles in the health and function of motor neurons. For example, GARS1 provides instructions for making glycyl-tRNA synthetase, an enzyme crucial for protein synthesis in cells. Pathogenic changes in GARS1 can lead to impaired enzyme function, affecting motor neuron survival [PMID:33671228]. HSPB1 and HSPB8 produce heat shock proteins, which act as 'chaperones' helping other proteins fold correctly and protecting cells from stress. When these proteins are not functioning properly due to genetic variants, motor neurons can become vulnerable to damage and degeneration.
- GARS1 glycyl-tRNA synthetase 1
- HSPB1 heat shock protein family B (small) member 1
- HSPB8 heat shock protein family B (small) member 8
Inheritance pattern
This type of hereditary motor neuropathy follows an autosomal dominant inheritance pattern. This means that a person only needs one altered copy of the responsible gene to develop the condition. If a parent has the condition, there is a 50% chance with each pregnancy that their child will inherit the altered gene and therefore potentially develop the condition. The condition can also arise from a new (de novo) genetic alteration that occurs for the first time in an individual, with no history in the family.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of hereditary motor neuropathy (distal, dominant) typically begins with a clinical examination by a neurologist, assessing muscle strength, reflexes, and sensory function. Electromyography (EMG) and nerve conduction studies (NCS) are often performed to evaluate nerve and muscle function, which can help differentiate HMN from other neuromuscular conditions. A definitive diagnosis is confirmed through genetic testing, which looks for pathogenic variants in genes known to cause HMN, such as GARS1, HSPB1, and HSPB8. Referrals for genetic testing in the UK can be made via the NHS Genomic Medicine Service, often following assessment by a clinical genetics service. This testing is covered by specific R-codes, ensuring appropriate access for patients where clinical suspicion is high.
Management & lifestyle
While there is currently no cure for hereditary motor neuropathy (distal, dominant), management focuses on symptomatic relief and improving quality of life. A multidisciplinary team, which may include neurologists, physiotherapists, occupational therapists, and orthotists, often provides care. Physiotherapy can help maintain muscle strength, flexibility, and mobility, while occupational therapy can provide strategies and adaptive equipment to assist with daily activities. Orthotic devices, such as ankle-foot orthoses (AFOs), can help manage foot drop. Regular follow-up with a neurologist is important to monitor disease progression and adjust management strategies as needed. Genetic counselling is also recommended for affected individuals and their families to understand the inheritance pattern and reproductive risks.
UK care pathway
In the UK, individuals suspected of having a hereditary motor neuropathy would typically be referred to a neurologist for initial assessment. If a genetic cause is suspected, the patient may then be referred to a clinical genetics service. These services are part of the NHS Genomic Medicine Service and can arrange genetic testing. Genetic counsellors within these services provide essential support, explaining the condition, inheritance patterns, and implications for the wider family. Genetic tests for these conditions are available through the NHS Genomic Laboratory Networks, with specific R-codes guiding the testing pathway.
Frequently asked questions
What is the difference between hereditary motor neuropathy and Charcot-Marie-Tooth disease?
Hereditary motor neuropathy (HMN) primarily affects the motor nerves, leading to muscle weakness and wasting, while sensory nerves are generally spared. Charcot-Marie-Tooth (CMT) disease, in contrast, typically affects both motor and sensory nerves, meaning it can cause both muscle weakness and problems with sensation, such as numbness or tingling.
Will my children inherit hereditary motor neuropathy?
Hereditary motor neuropathy (distal, dominant) follows an autosomal dominant inheritance pattern. This means if you have the condition, there is a 50% chance with each pregnancy that your child will inherit the altered gene. A genetic counsellor can provide detailed information about your specific family risks.
Is there a cure for hereditary motor neuropathy?
Currently, there is no cure for hereditary motor neuropathy. However, management focuses on alleviating symptoms and maintaining function through supportive therapies such as physiotherapy, occupational therapy, and the use of orthotic devices. Research into potential treatments is ongoing.
When do symptoms of hereditary motor neuropathy typically start?
The age of onset for hereditary motor neuropathy (distal, dominant) can vary significantly. Symptoms often begin in childhood or adolescence but can sometimes appear later in adulthood. The specific gene involved can influence the typical age of onset and progression rate.
What kind of doctors treat hereditary motor neuropathy?
Individuals with hereditary motor neuropathy are typically managed by a team of healthcare professionals. This team often includes neurologists, who specialise in nervous system disorders, along with physiotherapists, occupational therapists, and genetic counsellors. Orthotists may also be involved for specific equipment needs.