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Healthcare Professional Portal

In response to a recognised need for increased awareness of NDM,6 our goal is to help healthcare professionals recognise NDM more confidently by broadening understanding of the physical, emotional and practical impact of NDM on those it affects.

As rare doesn’t mean never, equip yourself with NDM knowledge today to help your patients tomorrow.

What is NDM?

Non-dystrophic myotonias (NDMs) are rare neuromuscular disorders, characterised by debilitating muscle stiffness (myotonia) and caused by mutations in sodium or chloride ion channels in the muscle cell membrane.1-3

The prevalence of NDM varies by country but is estimated to be 1 in 100,000 people in the EU.1 Although NDM can be referred to as ultra-rare, the impact it has on individual patients is considerable,4 with most experiencing daily symptoms, including muscle stiffness (myotonia) and pain.

Being ultra-rare, NDM can easily be misdiagnosed and/or misunderstood, even by those who are experienced in neuromuscular disorders. People with NDM frequently wait for 10 years or more before being correctly diagnosed.5

We want to improve this situation through collaboration with all those who have an interest in improving diagnosis and care for people with NDM.

Pathophysiology of myotonia in NDM

People with NDM carry inherited genetic mutations in voltage-gated ion channels that co-ordinate and control skeletal muscle contraction and relaxation.7

NDM include sodium channelopathies, which occur when the SCN4A gene is mutated, and chloride channelopathies when the mutation is in the CLCN1 gene.8

For patients, these ion-channel mutations lead to muscle membrane hyperexcitability, causing delayed muscle relaxation after voluntary contraction or percussion.9

NDM-related myotonia exclusively affects skeletal muscle and may occur more frequently when movement is suddenly initiated after a resting period; however, symptoms and symptom triggers can vary between NDM subtypes.9,10

Inheritance and genetics

NDM covers a group of inherited genetic disorders. Each NDM subtype shares the same muscle stiffness symptom of myotonia, but each has a different pattern of inheritance, channelopathy, triggers and location of muscle symptoms.1,9 Thomsen myotonia congenita, paramyotonia congenita, dyskalemic episodic paralysis and potassium-aggravated myotonia are inherited in an autosomal-dominant manner, while Becker myotonia congenita is an autosomal-recessive disorder.1,9 Family history should be considered whenever a patient presents with suspected NDM.

Autosomal dominant inheritance of Thomsen myotonia congenita, paramyotonia congenita, dyskalemic episodic paralysis and potassium aggravated myotonia.

Autosomal recessive inheritance of Becker myotonia congenita

Physical and psychosocial burdens of NDM

NDM is an ultra-rare disease that has a significant negative impact on the quality of life of people with the disease and detrimentally affects the people who care for them.5

People with NDM may struggle to exercise or even carry out simple movements such as walking up the stairs.2

Although muscle stiffness or muscle locking (myotonia) is the common symptom shared by all NDM subtypes, the full physical effects of NDM are broad and can also include cramps, myalgia, transient weakness, fatigue, muscle hypertrophy, dysphagia, and dysphonia.2 Myotonia causes obvious movement difficulties, such as problems with walking, running, and climbing stairs, or difficulty re-opening eyes or grip release after a handshake,6 but hidden symptoms of NDM, including pain and fatigue, also have negative effects on general health perception, vitality, physical and social functioning.4

 

Struggling to open your hand after clenching your fist may be a sign that you have NDM.6

In the 2020 Impact of non-dystrophic Myotonia on Patients and Caregivers’ quality of life (IMPACT) survey conducted in Europe and the USA, the majority of patients with NDM (N=181) experienced daily or continuous limb muscle stiffness (myotonia) and mobility problems, while nearly half said they had continuous tiredness and pain.5,11 Other patient-reported symptoms, occurring at least sometimes, included gastrointestinal issues (69%), being unable to open eyes after sneezing/ blinking (64%), a risk of dropping drinks (62%), and dysphagia when consuming cold drinks or food (45%).

Muscle symptoms have physical, social, practical and study/employment implications for people with NDM.3,5,8,11 In particular, problems with using public transport, embarrassment about symptoms and social anxiety5,8,11 can cause feelings of helplessness, isolation or the need to rely on others.

The IMPACT survey found that 27% of respondents rated their health-related quality of life as low.5,11

The considerable burden of NDM is further carried by family and friends; 45% of caregivers who responded to the IMPACT survey reported that they spend ≥5 hours per week caring for someone with NDM, with 29% spending ≥10 hours per week.11 The responsibility of caregiving had negative mental health impacts on 42%, and 25% reported that their physical health is affected.5

Long patient journey to diagnosis

People with NDM often face a long journey to receive a diagnosis and appropriate healthcare intervention.

Although signs of NDM manifest during childhood or early adulthood,10 mild and transient symptoms may be initially overlooked, for example falls and an abnormal gait are dismissed as normal during paediatric development.4,5,12 Therefore, unless other relatives have been diagnosed with (and are therefore aware of) NDM, pathological signs can go unrecognised for several years.5

In the absence of a known genetic risk and family screening, the NDM medical journey typically begins in a primary or general medical clinic. However, NDM is rarely encountered outside neuromuscular specialist centres and so may not initially be considered as a diagnosis. Furthermore, patients may report non-specific symptoms eg “tight muscles” or “weakness”5 that prompt referrals to healthcare professionals without awareness or the specialist knowledge needed to recognise possible NDM.

Overall, people with NDM frequently experience diagnostic delays of 10 to 17 years.5,10 Improving the early and accurate detection of NDM – reducing the time patients and their families spend searching for answers – remains a significant need.

NDM is formally diagnosed and managed in specialist neuromuscular centres, but the patient journey may start years before with nonspecific or unusual features. General medical professionals are therefore the gateway to the specialist care that people with NDM rely on to live the best life possible.

References
  • Hahn C & Salajegheh MK. Iran J Neurol 2016;15:46–53.
  • Stunnenberg BC, et al. Muscle Nerve. 2020;62:430–444.
  • Trivedi JR, et al. Exp Neurol. 2014;253:28–30.
  • Trip J, et al. J Neurol 2009;256:939–47.
  • Diaz-Manera J, et al. EMJ Neurol. 2021;6:37-46.
  • Auranen M, et al. EMJ Neurol. 2022;10:66-77.
  • Jitpimolmard N et al. Curr Treat Options Neurol. 2020;22:34.
  • Matthews E, et al. Pract Neurol. 2021;21:196-204
  • Matthews E, et al. Brain. 2010;133:9-22.
  • Vereb N, et al. J Neurol. 2021;268(5):1708-20.
  • Diaz-Manera J, et al. 16th International Congress on Neuromuscular Diseases (ICNMD) 2021a, Virtual meeting, 21-22, 28-29 May. ePoster: P742.
  • Matthews E, et al. J Pediatr. 2017;188:181-5.e186

What’s your NDM story?

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Foods to avoid on a low-potassium diet*

  • Fruit1,2
  • Vegetables1,2
  • Beans/legumes1,3
  • Other1-3
  • Avocado
  • Artichoke
  • Baked beans
  • Bran cereal
  • Apricots
  • Beetroot
  • Kidney beans
  • Dairy (eg yoghurt, milk)†
  • Bananas
  • Brussel sprouts
  • Lentils
  • Nuts
  • Dried fruits eg dates, raisins and prunes
  • Broccoli (cooked)
  • Brown rice
  • Grapefruit
  • Okra
  • Salt substitutes
  • Kiwi
  • Parsnip
  • Wholewheat bread and pasta
  • Mango
  • Potatoes (processed or with skin on)
  • Melons
  • Cooked spinach
  • Nectarines
  • Tomato (concentrated, eg. Tomato puree)
  • Oranges and orange juice
  • Papaya
  • Pomegranate and pomegranate juice

  • Fruit1,2

    Avocado

    Apricots

    Bananas

    Dried fruits eg dates, raisins and prunes

    Grapefruit

    Kiwi

    Mango

    Melons

    Nectarines

    Oranges and orange juice

    Papaya

    Pomegranate and pomegranate juice

  • Vegetables1,2

    Artichoke

    Beetroot

    Brussel sprouts

    Broccoli (cooked)

    Okra

    Parsnip

    Potatoes (processed or with skin on)

    Cooked spinach

    Tomato (concentrated, eg. Tomato puree)

  • Beans/legumes1,3

    Baked beans

    Kidney beans

    Lentils

  • Other1-3

    Bran cereal

    Dairy (eg yoghurt, milk)†

    Nuts

    Brown rice

    Salt substitutes

    Wholewheat bread and pasta

*Meat and fish contain a moderate amount of potassium but they are an important source of protein so shouldn’t be avoided; †Dairy products contain potassium but are an important source of calcium so should be consumed in moderation
References
  • WebMD. Low-potassium diet: what to know? Available at: https://www.webmd.com/food-recipes/low-potassium-diet-foods ; Accessed March 2021
  • St Georges Kidney Patients Association. Eating on a low potassium diet. Available at: https://www.sgkpa.org.uk/main/eating-well-on-a-low-potassium-diet-2 ; Accessed March 2021
  • NHS. Information for people on a low potassium diet. Available at: https://www.nth.nhs.uk/content/uploads/2019/02/PIL1061-Information-for-people-following-a-low-potassium-diet-Final-11.02.19-LP.pdf ; Accessed March 2021
  • NDM type1
  • Symptoms2,3
  • Which type of ion channel? 2,3
  • How is it inherited?2,3

  • Thomsen myotonia congenita

    (also called Thomsen myotonia or autosomal dominant myotonia congenita)
  • Lower limbs tend to be more affected, although can also affect the arms, hands and face. Stiffness may be worse when you first try to move after a period of inactivity, and may ease as you ‘warm up’.
  • Chloride (Cl-)
  • Autosomal dominant

  • Becker myotonia congenita

    (also called Becker myotonia, Becker disease, generalized myotonia, recessive generalized myotonia or autosomal recessive myotonia congenita
  • Lower limbs tend to be more affected, although can also affect the arms, hands and face. Stiffness may be worse when you first try to move after a period of inactivity, or if you are startled, and may ease as you ‘warm up’. Sometimes people with Becker myotonia congenita experience temporary weakness after an episode of myotonia.
  • Chloride (Cl-)
  • Autosomal recessive

  • Paramyotonia congenita

    (Also called Eulenburg disease, paralysis periodica paramyotonia, paramyotonia congenita of von Eulenburg, PMC or von Eulenburg’s disease)
  • Myotonia mainly affects hands and face and gets worse with exercise. Cold is also a key trigger of myotonia, and muscle weakness after an episode of myotonia may last hours or sometimes days.
  • Sodium (Na+)
  • Autosomal dominant

  • Sodium channel myotonia, SCM:

    myotonia permanens and myotonia fluctuans, acetazolamide-responsive myotonia (ARM) previously known as Potassium aggravated myotonias (PAM)
  • Potassium-aggravated myotonia is a rare form of NDM that affects all areas of the body. Myotonia attacks are triggered by eating potassium-rich foods. Symptoms may fluctuate widely from day to day (myotonia fluctuans) or are constant and severe (myotonia permanens).
  • Sodium (Na+)
  • Autosomal dominant

  • Other closely related sodium disorders with myotonia

    (including hyperkalemic paralysis or hyperPP)
  • Myotonia is usually mild, and often involves the eyelids, hands, and tongue. Attacks of weakness can occur at any time and are commonly triggered by rest following exercise, fasting, eating potassium-rich foods or stress.
  • Sodium (Na+)
  • Autosomal dominant
References
  • Stunnenberg B. Muscle Nerve. 2020 Oct; 62(4): 430–444
  • Hahn C, Salajegheh MK. Iran J Neurol 2016;15:46–53
  • Matthews E, et al. Brain 2010:133; 9–22

  • NDM type1

    Thomsen myotonia congenita

    (also called Thomsen myotonia or autosomal dominant myotonia congenita)

    Becker myotonia congenita

    (also called Becker myotonia, Becker disease, generalized myotonia, recessive generalized myotonia or autosomal recessive myotonia congenita

    Paramyotonia congenita

    (Also called Eulenburg disease, paralysis periodica paramyotonia, paramyotonia congenita of von Eulenburg, PMC or von Eulenburg’s disease)

    Sodium channel myotonia, SCM:

    myotonia permanens and myotonia fluctuans, acetazolamide-responsive myotonia (ARM) previously known as Potassium aggravated myotonias (PAM)

    Other closely related sodium disorders with myotonia

    (including hyperkalemic paralysis or hyperPP)

  • Symptoms2,3

    Lower limbs tend to be more affected, although can also affect the arms, hands and face. Stiffness may be worse when you first try to move after a period of inactivity, and may ease as you ‘warm up’.

    Lower limbs tend to be more affected, although can also affect the arms, hands and face. Stiffness may be worse when you first try to move after a period of inactivity, or if you are startled, and may ease as you ‘warm up’. Sometimes people with Becker myotonia congenita experience temporary weakness after an episode of myotonia.

    Myotonia mainly affects hands and face and gets worse with exercise. Cold is also a key trigger of myotonia, and muscle weakness after an episode of myotonia may last hours or sometimes days.

    Potassium-aggravated myotonia is a rare form of NDM that affects all areas of the body. Myotonia attacks are triggered by eating potassium-rich foods. Symptoms may fluctuate widely from day to day (myotonia fluctuans) or are constant and severe (myotonia permanens).

    Myotonia is usually mild, and often involves the eyelids, hands, and tongue. Attacks of weakness can occur at any time and are commonly triggered by rest following exercise, fasting, eating potassium-rich foods or stress.

  • Which type of ion channel? 2,3

    Chloride (Cl-)

    Chloride (Cl-)

    Sodium (Na+)

    Sodium (Na+)

    Sodium (Na+)

  • How is it inherited?2,3

    Autosomal dominant

    Autosomal recessive

    Autosomal dominant

    Autosomal dominant

    Autosomal dominant

References
  • Stunnenberg B. Muscle Nerve. 2020 Oct; 62(4): 430–444
  • Hahn C, Salajegheh MK. Iran J Neurol 2016;15:46–53
  • Matthews E, et al. Brain 2010:133; 9–22