It’s a fact that most people with HNPP know, but there are suggestions that certain exercises can actually do more damage than good. From walking to some types of yoga, while most forms of physical activity are encouraged by gym instructors, our bodies tend to rebel from the norm. But can exercise actually induce HNPP, even though it’s generally thought to be an hereditary condition?
As HNPP is an autosomal dominant disorder in which the condition is inherited and there is a deletion of one of the genes associated with PMP22, a child of an affected individual is at a 50 per cent risk of being affected by the condition. This suggests that the likelihood of a person developing HNPP out of nowhere is relatively low.
What are ‘sporadic’ cases of HNPP?
There have been recent reports that state that a few types of muscle training has actually brought about sporadic symptoms of HNPP without any previous familial history of the condition. Sporadic cases due to de novo deletion accounted for 21 per cent of the investigated HNPP families, as reported by some studies. De novo mutation is an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell of one of the parents or in the fertilised egg itself.
According to a 2017 study carried out by researchers at the Department of Neurology and Rheumatology, Shinshu University School of Medicine, Matsumoto, Japan, this apparently was the case in a 15-year-old boy. The authors suggest that this is the first instance of an adolescent “that developed neurological symptoms during muscle training in a school baseball club activity”, the first signs in a sporadic case of HNPP. The teenager developed bilateral painless brachial plexopathy through short-term barbell training and plank exercises.
“Patients sometimes show an atypical clinical phenotype, and a diagnosis of HNPP can therefore be challenging, especially in sporadic cases as in our patient.”
“Muscle Training-induced Bilateral Brachial Plexopathy in an Adolescent with Sporadic HNPP” – Kodaira, M., et al – July 2017
While brachial plexopathy can be a common feature of HNPP, bilateral involvement is thought to be unusual because HNPP is usually associated as a mononeuropathic condition, where there is a focus in only one area of nerves.
The authors in this case say: “As his clinical and NCS [nerve conduction study] findings indicated muscle training-induced bilateral brachial plexopathy in HNPP, genetic analysis for this disorder was performed, which revealed deletion of the PMP22 gene. Patients sometimes show an atypical clinical phenotype, and a diagnosis of HNPP can therefore be challenging, especially in sporadic cases as in our patient.”
The major difference in this occasion is that not only did he suffer from a bilateral injury, he also developed a sporadic case of HNPP triggered by relatively straightforward exercises. This is unlike some of the other examples where those in military training are far more likely to develop symptoms linked to HNPP, due to the strenuous physical activity undertaken by soldiers. However, this is not the first time ‘push ups’ are seen to be the main culprit as a trigger.
In another 2017 report A Case of HNPP due to Push-up Exercise, a 17-year-old man with no familial history of the condition developed “motor and sensory disturbance of the left upper limb a few days after starting push-up exercise”. Scientists from the Department of Neurology, Hirosaki University Graduate School of Medicine, say that the patient also developed brachial plexopathy, similar to the case above.
In the abstract, they conclude that: “Genetic tests revealed a diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP). HNPP should be included in the differential diagnosis for neuropathy due to slight exercise or nerve compression even when familial history is negative.”
The original text is in Japanese – read full document here.
Researchers from the Division of Neurology and the Department of Pathology, University of Missouri School of Medicine, Columbia, USA, found a case in 2004 akin to the above studies. A 21-year-old in good health began to develop symptoms of HNPP on her first day of military training. She began to show symptoms of severe pain, weakness, and atrophy in her right shoulder, foot and hands. Her mother and her family had no history of neuromuscular disease. She did not know her father or his family history.
Researchers of the study Fulminant Development with Axonal Loss during Military Training say that the patient’s symptoms were “unique” and that she did not have the “cardinal features of HNPP” including inheritance and mononeuropathy.
They say: “While the presentation and severity of this patient’s condition may relate to a specific unknown genetic profile with very low PMP-22 mRNA levels, Schenone et al, in finding correlations between reduced PMP-22 mRNA levels and disease severity, also suggested that extrinsic factors—for example, level of physical activity, may be important in determining phenotypic features.
“This appears to be true of our patient—that she was neurologically normal, then developed symptoms on the first day of military physical training with progression as she continued the training over a three week period, suggests that disease severity and focal axonal damage were related to these intense activities.”
The authors add: “Additionally, as it has recently been recognised that sporadic cases of HNPP are common, either because of de novo mutations or asymptomatic carriers, her lack of family history did not preclude this diagnosis.”
How likely is it that a case of HNPP is sporadic?
It’s important to note that HNPP may not be easily traced in other family members, which means while it may appear sporadic, it could just have been overlooked. A 2013 case report reiterates this view, with authors saying that approximately one-third of deletion carriers are unambiguously detected on the basis of “electrophysiological criteria and confirmed by genetic analysis are asymptomatic and do not display significant signs at clinical examination.”
Researchers from Department of Paediatrics, Hospital de Guimarães, Portugal, say: “Thus, the family history is often uninformative, and a significant proportion of probands may be considered as apparently sporadic cases. However, a close questioning and examination of the relatives provided evidence for autosomal dominant inheritance in families that were originally stated by the probands to be normal. Therefore, HNPP can easily be overlooked in those cases in which familial involvement is not recognised unless intensive ascertainment techniques are used.”
Electrophysiologic studies are said to be “suggestive” and not “sufficient for diagnosis” which may be why it may be imperceptible to locate.
How exercise can trigger symptoms
The more frequent representations are in those who already have familial histories of HNPP, or in those who have already been diagnosed. In one such case in 2005, hiking and athletic training brought on the symptoms. A 10-year-old girl, who suffered from acute, recurrent monoplegic episodes affecting both the sciatic nerves and the left brachial
plexus since the age of 7, showed quite a lot extensive symptoms from relatively low impact exercise.
Authors from the Department of Paediatrics, Yokohama City University Medical Centre, Japan, say: “This school child having HNPP is considered to be susceptible to the influence of abundant physical training, rather than minor trauma or compression at sites of entrapment of peripheral nerves.” However, this is hardly surprising given the nature of the condition. What’s more unusual are the situations where HNPP is not present beforehand or without familial background.
It goes without saying, exercise can cause many types of injuries even for those without HNPP depending on how extreme it may be. And as we have seen above, there have been at least several cases of ‘sporadic’ HNPP, which develops without any prior history of symptoms or familial connection.
However, it may be worth noting that without the correct tests to detect hereditary links, these may be incorrectly termed as ‘sporadic’. That being said, there have been established reports that suggest at least 21 per cent of HNPP cases are de novo mutations, so it may not be out of the realms of possibility that certain types of exercise can induce symptoms of HNPP.