Prevalence of Neuromuscular Diseases in Young South Korean Males; A Korean Military Manpower Administration and Medical Command Data-Based Study

Abstract

Background and Purpose

All young males in South Korea must undergo a physical examination for their participation in military service. We aimed to determine the prevalence rate (PR) of various neuromuscular diseases in young South Korean males using the data of exempted patients and soldiers.

Methods

The number of males exempted based on specific items of physical examination corresponding to neuromuscular disease during 2011–2020 were obtained from the records of the Military Manpower Administration. The list of enlisted soldier patients who were discharged from military service due to neuromuscular diseases during 2011–2020 was obtained from the Armed Forces Medical Command, and their medical records were reviewed.

Results

The PR of neuromuscular diseases was calculated among 948 identified males: 713 exempted males and 235 soldiers. The PRs of overall hereditary neuropathies, Hirayama disease (HD), myasthenia gravis (MG), and inherited muscle diseases in South Korean males in their early 20s were 8.34 (95% confidence interval [CI], 7.39–9.30), 5.54 (95% CI, 4.76–6.32), 2.97 (95% CI, 2.40–3.55), and 10.38 (95% CI, 9.31–11.46) per 100,000 persons, respectively. Among the enlisted soldiers, hereditary neuropathy with liability to pressure palsy was the most common neuromuscular disease, with a prevalence among the enlisted soldiers of 3.11 (95% CI, 2.42–3.80) per 100,000 persons. Myotonic dystrophy was the most prevalent myopathy, followed by facioscapulohumeral muscular dystrophy.

Conclusions

The 10-year PRs of hereditary polyneuropathies, HD, MG, and inherited muscle diseases in young South Korean males have been reported. These data could be valuable to understanding each neuromuscular disease in the young male population of South Korea.

INTRODUCTION

All males in their late teens in South Korea must undergo a physical examination before they are enlisted for military service. The number of males exempt from military service due to neuromuscular disease can therefore be identified from the records of the Military Manpower Administration (MMA). Although many patients with neuromuscular diseases did not enter military service due to the results of physical examinations, many soldiers have also been diagnosed with such diseases during their military service and discharged by the review committee. The total number of those exempted from military service during their physical examination and those discharged from military service due to neuromuscular disease can be used to determine the prevalence rate (PR) of each neuromuscular disease among South Korean males in their early 20s.

The analysis of the medical data of these soldiers can provide additional prevalence data for neuromuscular diseases newly diagnosed in the early 20s, and their types and clinical characteristics. For example, hereditary neuropathy with liability to pressure palsy (HNPP) is frequently diagnosed in soldiers.¹,² A previous study in South Korea identified 36 HNPP cases diagnosed during military service.³ There have been some reports of myotonic dystrophy (MD), myotonia congenita, and paramyotonia congenita among soldiers in Finland.⁴ However, the type and prevalence of neuromuscular diseases that can be diagnosed in young male soldiers have not received much attention.

This study aimed to determine the PRs of various neuromuscular diseases in South Korean males in their early 20s using the data on young South Korean soldier patients diagnosed with various neuromuscular diseases along with those of exempted males due to neuromuscular diseases obtained from the record of the MMA. We also described the clinical characteristics of young South Korean soldier patients with various neuromuscular diseases diagnosed during their military service.

METHODS

Study population and data extraction

Information about the number of males exempt from military service based on specific items of physical examination corresponding to neuromuscular diseases over a 10-year period (2011–2020) was obtained from the records of the MMA through the public information portal (https://www.open.go.kr/). According to the Standards for Assessing Diseases and Physical or Mental Illness in the Enforcement Decree of the Military Service Act, we included the following diseases: chronic peripheral polyneuropathy including genetic polyneuropathy (88-C), ocular-type (89-B) or generalized-type (89-C) myasthenia gravis (MG), muscular diseases such as progressive muscular dystrophies and congenital myotonia (90-C), benign focal amyotrophy, also known as Hirayama disease (HD) (91-A), and other motor neuron diseases (91-B) (Table 1). Acute inflammatory polyneuropathies such as Guillain-Barré syndrome and acquired focal peripheral neuropathy or injuries were excluded; only patients with long-term functional disabilities due to those diseases were exempt according to the act, so the number of those exempt cannot reflect the prevalence of those diseases.

Table 1. Relevant provisions in this study from the Standards for Assessing Diseases and Physical or Mental Illness in the Enforcement Decree of the Military Service Act of South Korea.

Diseases and physical or mental illness			Physical grade*
88.† Multiple peripheral neuropathy
	A. Acute (except Guillain-Barré syndrome) (details skipped)
	B. Guillain-Barré syndrome (details skipped)
	C. Chronic
		1) Mild neurological disability (abnormalities in electrophysiological study and sensory or motor disability; difficulty in performing military service	5
		2) Moderate or severe neurological disability (considerable difficulty in performing the activities of daily living)	6
		3) Genetic peripheral polyneuropathy (confirmed by genetic or electrophysiological study)	5
	D. Complex regional pain syndrome (details skipped)
89. MG
	A. Diagnosed as MG in the past but treatment not required until now
	B. Ocular type		5
	C. Generalized type		6
90. Muscle disease
	A. Periodic paralysis (details skipped)
	B. Inflammatory myopathy (details skipped)
	C. Other myopathy (progressive muscular dystrophy, congenital MD, and the other severe myopathy)
		1) Mild sequel (difficulty in performing military service)	5
		2) Moderate or severe sequel (considerable difficulty in performing the activities of daily living)	6
91. Motor neuron disease
	A. Benign focal amyotrophy (HD)		5
	B. Motor neuron disease
		1) Mild motor disability	5
		2) Moderate or severe motor disability	6

^*Physical grade 5 or 6 was exempted from military service due to disease or physical or mental illness; ^†Numbers refer to items of physical examinations in the provision.

HD, Hirayama disease; MD, myotonic dystrophy; MG, myasthenia gravis.

The list of enlisted soldier patients who had been reviewed for discharge due to neuromuscular diseases corresponding to the above items of physical examination over a 10-year period (2011–2020) was obtained from the Armed Forces Medical Command. Patients who had been diagnosed with such neuromuscular diseases but did not want to apply for the review of discharge from military service were also identified among the patients who underwent electrophysiological study at the Armed Forces Capital Hospital. Officers were excluded, with only soldiers at the ranks of trainee, private, private first class, corporal, and sergeant being included. Data on basic demographics, symptom onset, diagnostic study results, and the duration between the initial visit to a military hospital and the date of the committee review for discharge were investigated through reviewing their medical records.

Statistical analyses

The PR of each disease was calculated as the number of cases divided by the number of person-years of risk, which is expressed as cases per 100,000 persons. The denominator of PR for males in their early 20s was the number of 20-year-old South Korean males obtained during 2011–2020 from the Korean Statistical Information Service. The denominator of PR among the enlisted soldiers was the number of total enlisted soldiers who entered military service during 2011–2020. The 95% confidence intervals (CIs) were calculated using the standard formula for normal approximation of the binomial distribution (p±1.96×√p(1-p)/n). Descriptive statistical analysis was performed and the differences in characteristics between two groups were identified using the χ² test in IBM SPSS software version 25 (IBM Corp., Armonk, NY, USA). Significance was set at p<0.05.

Ethics statement

This study was approved by the Ethics Review Committee of the Armed Forces Medical Command (IRB No. AMFC-202104-HR-020-03) and the requirement to obtain informed consent was waived.

RESULTS

The PR of neuromuscular diseases were calculated among 948 identified males: 713 who were exempt from military service based on the corresponding clauses from the MMA over a 10-year period, and 235 who were from the military medical review. Table 2 lists the numbers of patients exempted or discharged according to each item of physical examination.

Table 2. PRs among the South Korean male population in their early 20s during 2011–2020.

Neuromuscular disease (numbers referring to items of physical examinations)		Frequency among the exempted	Frequency among the enlisted soldiers	Total frequency	PR among males in their early 20s per 100,000 (95% CI)	PR among enlisted soldiers per 100,000 (95% CI)
Peripheral polyneuropathy (88-C-1, -2, -3)		192	97	289	8.34 (7.38–9.30)	3.87 (3.10–4.64)
	HNPP		78			3.11 (2.42–3.80)
Hirayama disease (91-A)		157	35	192	5.54 (4.76–6.32)	1.40 (0.93–1.86)
Myasthenia gravis		68	35	103	2.97 (2.40–3.55)	1.40 (0.93–1.86)
	Ocular type (89-B)	61	22	83	2.39 (1.88–2.91)	0.88 (0.51–1.24)
	Generalized type (89-C)	7	13	20	0.58 (0.32–0.83)	0.52 (0.24–0.80)
Inherited muscle disease (90-C-1, -2)		296	64	360	10.38 (9.31–11.46)	2.55 (1.93–3.18)
	Myotonic dystrophy		28			1.12 (0.70–1.53)
	Facioscapulohumeral muscular dystrophy		8			0.32 (0.10–0.54)

CI, confidence interval; HNPP, hereditary neuropathy with liability to pressure palsy; PR, prevalence rate.

The patients identified in the military medial review were all male, and were aged 20.6±1.4 years (mean±SD). The most common military rank among the patients at the time that they had a committee review for discharge was private first class (53.2%), followed by private second class (20.0%), corporal (19.1%), and sergeant (7.7%). Seven patients who did not apply for committee review for discharge despite being diagnosed were included (three sergeants, two corporals, one private first class, and one private second class). The number and clinical characteristics of the patients according to their diagnosis are presented in Tables 2 and 3.

Table 3. Numbers and characteristics of patients diagnosed with neuromuscular diseases among young South Korean male soldiers during 2011–2020.

		Frequency	Symptom onset		Family history		Duration between initial visit to military hospital and date of committee review for discharge (days)
			Before military service	During military service	Yes	No or unknown	Mean (range)
Peripheral polyneuropathy
	HNPP	78	9	69	11	67	121.7 (8–554)
	CMT type 1A	6	3	3	0	6	100.7 (20–302)
	CMT type 2 or X	5	5	0	3	2	169.2 (49–287)
	Polyneuropathy without genetic result	8	3	5	4	3	166.9 (20–302)
Motor neuron disease
	Hirayama disease	35	21	14	0	35	112.9 (21–562)
	Spinal muscular atrophy	3	3	0	1	2	125.7 (69–169)
	Amyotrophic lateral sclerosis	1	0	1	0	1	97
Myasthenia gravis
	Ocular type	22	7	15	0	22	111.9 (17–475)
	General type	13	6	7	0	13	71.8 (15–215)
Inherited muscle disease (with myotonia)
	Myotonic dystrophy	28	22	6	16	12	82.0 (15–303)
	Paramyotonia congenita	2	2	0	2	0	112.5 (111–134)
	Myotonia congenita	1	1	0	1	0	50
	Other myotonia	8	7	1	5	3	158.0 (38–496)
Inherited muscle disease (without myotonia)
	Facioscapulohumeral muscular dystrophy	8	8	0	4	4	131.3 (44–226)
	Becker muscular dystrophy	3	3	0	0	3	144.7 (38–220)
	Distal myopathy	3	0	3	1	2	57.3 (41–66)
	Metabolic myopathy	3	1	2	1	2	215.0 (157–301)
	Other myopathy (type unknown)	8	5	3	0	5	100.6 (27–206)

CMT, Charcot-Marie-Tooth; HNPP, hereditary neuropathy with liability to pressure palsy.

Peripheral polyneuropathies

Hereditary polyneuropathies caused 289 males to be exempted at the MMA or discharged from military service, and its PR among males in their early 20s in South Korea during 2011–2020 was 8.34 (95% CI, 7.38–9.30) per 100,000 persons (Table 1).

HNPP was the most frequent diagnosis among the soldiers (78 cases), with a PR among the enlisted soldiers during 2011–2020 of 3.11 (95% CI, 2.42–3.80) per 100,000 persons. Symptoms began to appear after entering military service in 88.5% of the patients. Gene analysis was performed on 74 patients, 70 of whom (94.9%) had typical PMP22 deletion, while the remaining 4 had other point mutations.

Other-type genetic peripheral polyneuropathy was identified in 11 cases: Charcot-Marie-Tooth (CMT) type 1A with PMP22 duplication (6 cases), type 2 with MFN2 mutation (3 cases), and type X with GJB1 mutation (2 cases). Eight cases were diagnosed as chronic generalized peripheral polyneuropathy, for which a specific genetic abnormality had not been identified.

Hirayama disease

Benign focal amyotrophy, also known as HD, was identified in 192 patients among those exempted at the MMA and those discharged from military service, and its PR among those in their early 20s in South Korea during 2011–2020 was 5.54 (95% CI, 4.76–6.32) per 100,000 persons. Overall, 18.2% (35 out of 192) of the cases were diagnosed during their military service. HD was the second most prevalent disease along with MG in the soldier patients. Hand weakness started before entering military service in 60.0% of the soldier patients.

Myasthenia gravis

MG caused 103 males to be exempted at the MMA or discharged from military service. Its PR among South Korean males in their early 20s during 2011–2020 was 2.97 (95% CI, 2.40–3.55) per 100,000 persons. The PRs for ocular- and generalized-type MG were 2.39 (95% CI, 1.88–2.91) per 100,000 persons (80.6%) and 0.58 (95% CI, 0.32–0.83) per 100,000 persons (19.4%), respectively.

There were 22 cases of ocular-type MG (62.9%) and 13 of generalized-type MG (37.1%) among the soldier patients. The percentages of positive results for the ocular and generalized types of MG obtained through the neostigmine test (72.7% vs. 61.5%) and the repetitive nerve stimulation test (40.9% vs. 53.8%) did not differ significantly. However, the percentage of positive acetylcholine receptor antibody was significantly higher in generalized-type MG (69.2%) than in ocular-type MG (27.3%) (p=0.019). Thymoma was detected in two cases of generalized-type MG.

Inherited muscle diseases

There were 360 males who were exempted at the MMA or discharged from military service due to inherited muscle diseases. The PR for all inherited muscle diseases among South Korean males in their early 20s during 2011–2020 was 10.38 (95% CI, 9.31–11.46) per 100,000 persons.

MD was the most prevalent inherited muscle disease among the soldier patients, being identified in 28. The PR for MD among the enlisted soldiers during 2011–2020 was 1.12 (95% CI, 0.70–1.53) per 100,000 persons. All cases were classified as MD type 1, as confirmed by amplified CTG repeats in DMPK, except for one case with limb-girdle MD who had an abnormality in CAV3. Symptoms started before entering military service in 78.5% of the patients. Hand myotonia was the most common symptom, presenting in 85.7% of MD cases. Two patients complained of leg myotonia, while two others were diagnosed with MD while receiving treatment for pneumonia.

Facioscapulohumeral dystrophy (FSHD) was the most common myopathic disorder in cases of inherited muscle diseases without myotonia, with a PR among the enlisted soldiers of 0.32 (95% CI, 0.10–0.54) per 100,000 persons. Symptoms were present before entering military service in all cases, and D4Z4 mutation was confirmed in four cases. There were three cases of Becker muscular dystrophy, three of distal myopathy, three of metabolic myopathy, and eight of unclassified myopathy.

DISCUSSION

South Korea is a country with compulsory conscription that operates a strict system to prevent draft dodging. All South Korean males are required to undergo a military service judgment test at 19 years old, which can only be postponed in cases of studying abroad, mental or physical illness, natural disaster, or arrest. In the case of peripheral nervous system illnesses, medical records and electrophysiological test results including the raw data must be submitted to the MMA. Males with serious illness who are judged to be at physical grade 5 or 6 are exempted from military service. Males diagnosed during their military service are discharged by the medical investigation committee using the same standards for those exempted, after neurologists and various specialists review medical records, neuromuscular test results, and genetic test data if necessary.

This study has provided epidemiological data on the occurrence of hereditary polyneuropathies, HD, MG, and inherited muscle diseases in the South Korean young male population for a 10-year period using the data from those exempted and those discharged from military service. Combining the data of those exempted at the MMA and soldiers discharged from military service due to the same items of physical examination provided us with reliable and representative PR data for the South Korean male population in their early 20s. Although it was restricted to males in their early 20s, these data were not estimates calculated from sample data, but instead were more similar to survey data of the entire population of South Korea. Unlike other prevalence studies based on the number of patients diagnosed in hospitals, this study included some patients who would only visit the hospital for a physical examination. In countries with populations similar to that of South Korea, even if it narrowed down to specific sexes and ages, there is not much data that can identify the PRs of rare diseases for the entire population. A new PR was also suggested for some diseases that lacked research related to prevalence in South Korea. Although we could not specify the detailed diagnoses among peripheral polyneuropathies and inherited muscle diseases due to the clauses that contained collective terminology, the PRs for MG and HD were discrete valuable data that represented the South Korean male population in their early 20s with those diseases. Furthermore, the distribution of detailed diagnoses of peripheral neuropathies and muscle diseases among the soldier patients can provide us with information about the types of neuropathies and muscle diseases that can be newly diagnosed in the early 20s relatively healthy male population.

This study also discussed the PRs of rare specific neuromuscular diseases diagnosed in enlisted South Korean soldiers, who represented a young and relatively healthy male population. Considering the inadequate information about the PRs and characteristics of these rare neuromuscular diseases, the results could prove valuable in understanding such diseases in the South Korean young male population. The exact diagnosis of relatively common peripheral polyneuropathy or inherited muscle disease could be identified in these results among the soldier patients.

Among peripheral polyneuropathies, HNPP was identified in 78 male patients performing their military service during 2011–2020. This was the largest number of patients with HNPP ever reported, and its prevalence has been found to be 0.84–16/100,000 among studies that considered up to 69 cases.⁵,⁶,⁷ No actual prevalence data on patients with HNPP in South Korea are available, although one study calculated a PR of 58.9/100,000 for PMP22 deletion using next-generation sequencing-based copy-number variation analysis among newborns in South Korea, which was much higher than that in previous data.⁸ Symptoms of HNPP mostly occur in the 10s or 20s and are aggravated by strenuous activity. Proximal arm weakness due to brachial plexopathy was the most common symptom in our previous study of 36 South Korean soldiers with HNPP.³ Strenuous pushups, as either a punishment or an exercise, was the main causative event in patients having brachial plexopathy with HNPP, whereas it was rare in patients having that condition without HNPP.⁹ Many patients could therefore be detected and confirmed as having HNPP rather early by this distinct clinical feature, and we can assume that its PR among South Korean soldiers can also be safely extended to the general South Korean male population.

CMT is known as the most common hereditary peripheral polyneuropathy, with an average worldwide PR of 20 (ranged 3.1–82.3) per 100,000 persons, of which 51% are male.¹⁰ The PR for CMT was estimated to be 5.2/100,000 in South Korea in 2018.¹¹ However, CMT is less common than HNPP among male soldiers in their early 20s. Even if we assume that the cases without genetic results are CMT, the maximum number of cases would be 19 with a PR of 0.72/100,000 among enlisted soldiers, which is still much lower than that of HNPP. In the data of the males exempt from military service at the MMA, all peripheral polyneuropathies were counted under one item of physical examination, so we could not determine the exact diagnosis such as of CMT or HNPP. Considering the high prevalence of CMT, over half of those exempt from military service at the MMA may have been suffering from it. Cavus foot and the availability of a PMP22 duplication test may allow early diagnosis before the physical examination is conducted for military service. In contrast, HNPP was often diagnosed after acute paralysis events in this age group, so it might not be a common reason for exemption at the MMA.

HD is characterized by the juvenile onset of unilateral or asymmetric weakness and amyotrophy of the hand and forearm, and is most common in Asian males. The onset age is late 10s or early 20s, with the peak rate at 15–17 years.¹² Male-to-female ratios of 9.3–31.6:1 have been found, indicating male predominance.¹³ HD is therefore expected to be prevalent among soldiers who enlist in their early 20s. A nationwide survey in Japan during 1996–1998 identified 333 HD cases;¹² however, HD prevalence has not been reported for any country. Only a few case reports of HD have been presented in South Korea,¹⁴,¹⁵,¹⁶ and this was the first and the largest study reporting the 192 cases of HD in South Korea. HD is classified under one item of physical examination in the Standards for Assessing Diseases and Physical or Mental illness in the Enforcement Decree of the Military Service Act. We were therefore able to calculate HD prevalence among South Korean males in their early 20s from the total number of cases among enlisted soldiers and those exempted at the MMA. The peak at age 15–17 years means that most patients with HD were expected to be diagnosed before military service. However, 18.2% (35 out of 192) of the cases were diagnosed during their military service, among whom 60% presented their first symptom before entering service. Even though the exact PR of HD among the enlisted soldiers was relatively low, military hospitals still played some role in detecting patients who were yet to be diagnosed with HD.

The prevalence of MG in South Korea was found to be 9.67/100,000 in 2010 and 10.66/100,000 in 2011.¹⁷ Males younger than 20 years had a PR of 2.31–2.36/100,000, while those younger than 40 had a PR of 5.76–6.41/100,000. Our study found a PR of 3.10/100,000 for South Korean males in their early 20s, which was consistent with that found in other previous studies. The PRs of ocular- and generalized-type MG could also be calculated independently in this study due to the separate items of the standards in the Enforcement Decree. Approximately 80% of MG cases among males in their early 20s belonged to the ocular type. This result was also consistent with previous studies finding ocular and childhood MG cases to be more common in Asia.¹⁸ Notably, the rate of acetylcholine-receptor-antibody positivity was low in ocular-type MG, which was consistent with the findings of a previous South Korean study.¹⁹ That study found that 42.9% of postpubertal males were positive for acetylcholine receptor antibody, while it was 100% in postpubertal females. Thymoma was less frequent in postpubertal males (7.7%) than in postpubertal females (84.6%) in that study, which corresponded to our study results (5.7%).

We found MD to be the most common inherited muscle disease among the enlisted soldier patients. Its PR has been found to be 10 (ranged 7.1–26.5) per 100,000.¹⁰ The PR of MD was estimated to be 9.13/100,000 in Okinawa, Japan.²⁰ One study found 124 cases in a South Korean population, 57.2% of which were males;²¹ however, no prevalence data for MD are available yet. Although we could not obtain the PR from the data of those exempted due to the inability to differentiate MD from other muscular diseases, the result for enlisted soldiers was expected to represent most juvenile-onset MD cases in the early-20 male population.

FSHD is a relatively common muscular condition after MD, with a global PR of 4 (ranged 2.0–6.8) per 100,000 persons.¹⁰ However, there are no PR data for FSHD in the South Korean population. One study of 104 South Korean patients with FSHD found that 58.7% were male and that the median age at symptom onset was 13 years.²² All patients with FSHD in the present study recognized their symptoms before entering military service but had not received the correct diagnosis.

The present study had some weaknesses. First, we did not include data for young officers, and so the PR of South Korean males in their early 20s might not have been correct. However, officers are generally in better physical condition, so the number of missing cases is expected to be small and do not have any major impact on our results. Second, it is possible that we missed patients who received their diagnosis of neuromuscular diseases during military service but did not apply for the medical review of discharge from military service. There may also have been people with other diseases at the same time who were exempted applying a different item of physical examination. On the other hand, there may be patients who were reexamined and exempted due to new symptoms in their late 20s while enlistment was delayed, since information on age was not available in the data of the exempted. Third, the PR of the South Korean male population in their early 20s during 2011–2020 was calculated by adding the number of cases of enlisted soldiers with an average age of 20.6 years, as was the number of those exempt with an average age of 19 years or older because the draft physical examination was notified at this age. The total number of 20-year-old males in South Korea during 2011–2020 was used as the denominator. This time gap meant that this result does not exactly represent the PR among the entire 20-year-old population during 2011–2020. However, there were no overlapping data, and we calculated the PR across 10 years. We can therefore reliably assert that our study results closely reflect the current prevalence of neuromuscular diseases in the 20-year-old South Korean male population. Fourth, we could not review the medical reports of those exempted, so the analysis of PR in the overall South Korean male population in their early 20s was not available for some diseases. If the detailed information becomes available to researchers, it will help to understand the prevalence and characteristics of each specific disease in South Korean male populations. Fifth, the clinical findings were not presented for each disease because clinical data were not included in the records of the MMA. Studies are currently underway involving patients diagnosed after enlistment, including the clinical findings of each disease.

In conclusion, the PRs of hereditary polyneuropathies, HD, MG, and inherited muscle diseases in the South Korean young male population across 10 years have been presented using the data from enlisted soldier patients and those exempted from military service at the MMA. HNPP, HD, MG, MD, and FSHD are relatively common in young soldiers. These data could prove valuable to understanding the characteristics of each neuromuscular disease in the young male population of South Korea.

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.