Caregiver Burden with Duchenne and Becker Muscular Dystrophy in Japan: A Clinical Observation Study

Abstract

Objective

Skeletal muscle weakness and cardiomyopathy can be seen in carriers of dystrophinopathy. Therefore, the health management of caregivers of Duchenne/Becker muscular dystrophy (DMD/BMD) patients who are themselves carriers is an important issue. However, few studies have focused on caregivers who have dystrophin mutations.

Methods

In this cross-sectional study conducted at five hospitals, the daily living, situation medical treatment status, genetic testing, physical assessment, care burden, and quality of life of caregivers of DMD/BMD patients were surveyed.

Results

The subjects were 36 main caregivers (mean age 55.7±8.4 years old), of whom 52.8% were diagnosed as carriers, 8.3% were noncarriers, and 38.9% were not confirmed. In addition, half of the caregivers were not examined regularly at medical institutions. Of all caregivers, 54.3% had muscle or cardiac symptoms, and 75% had elevated serum creatine kinase levels. The mean Zarit Caregiver Burden Interview (ZBI) total score of current caregivers was 20.9±13.1. The frequency of a ZBI total score ≥25 was significantly higher in caregivers diagnosed as carriers than in caregivers unexamined as carriers (p=0.04). The health-related quality of life score (Short Form 36; SF-36) in caregivers was slightly lower than the Japanese standard scores in the sections of physical functioning, role limitations-physical, bodily pain, and social functioning.

Conclusion

Some caregivers of DMD/BMD patients can themselves have muscular or cardiac symptoms and a heavy care burden. It is therefore necessary for carrier caregivers, especially women, to undergo regular health checkups and receive appropriate health management.

Introduction

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive hereditary muscle diseases caused by mutations in the gene for the dystrophin protein (1,2). DMD patients develop severe, progressive weakness, become wheelchair-dependent in their early teens, and die at approximately 20-30 years old due to breathing complications or cardiomyopathy (3). Recent medical progress, including respiratory care, nutritional support, and cardioprotective agents, has extended the life expectancy of DMD patients (4-6), who are now spending a longer time at home. Accordingly, the aging of caregivers of dystrophinopathy patients and the extension of the care period have become serious problems.

Clinical symptoms, such as mild to severe muscle weakness, muscle atrophy, and cardiomyopathy, can be seen in carriers of dystrophinopathy who are classified as “manifesting carriers” (7,8). Lee et al. showed that 60% of mothers of DMD patients and 90% of mothers of BMD patients were carriers of mutations of the dystrophin gene (9). Caregivers of dystrophinopathy patients may be mothers or female siblings and can thus themselves be female dystrophinopathy carriers and have a risk of skeletal muscle weakness or cardiomyopathy.

In a previous report that analyzed 7 large studies, the prevalence of skeletal muscle damage in female dystrophinopathy carriers was 2.5-19%, and that of dilated cardiomyopathy was 7.3-16.7% for DMD and 0-13.3% for BMD patients (10). In particular, genetic testing of carriers is not often performed in Japan because of the complex ethical and social problems associated with hereditary diseases (11). Therefore, individuals who are undiagnosed carriers with clinical symptoms often care for dystrophinopathy patients. The mothers of DMD/BMD patients often bear not only a physical care burden but also a psychological burden due to feelings of guilt for passing on the disease to the patient (12). We consider the health management of caregivers to be an important issue, and the loss of their health can decrease the quality of life (QOL) of dystrophinopathy patients themselves.

Some studies have investigated the QOL and care burden of caregivers of DMD and BMD patients. A recent systematic literature review (including 21 articles) of caregiver burden in DMD showed that caregivers of patients with DMD had an impaired health-related QOL (HRQOL), poor sleep quality, reduced family function, depression, pain, stress, sexual dysfunction, and low self-esteem (13). However, few studies have focused on caregivers who have dystrophin mutations.

The present study therefore examined the daily living situation, medical treatment status and prevalence of genetic testing in caregivers of DMD/BMD patients. In addition, this study evaluated the presence of any muscle symptoms, presence of elevated serum creatine kinase (CK) and serum brain natriuretic peptide (BNP) levels, degree of caregiver burden, and QOL of DMD/BMD caregivers who were diagnosed as carriers and explored issues specific to carriers by comparing their outcomes to those of caregivers whose carrier status was not examined, caregivers proven to be noncarriers, and non-caregivers with female dystrophinopathy.

Materials and Methods

Study design and protocol approvals

This study was a cross-sectional survey conducted at five hospitals [National Hospital Organization (NHO) Kumamoto Saishun Medical Center, NHO Akita National Hospital, NHO Matsumoto Medical Center, NHO Tokushima National Hospital, NHO Osaka Toneyama Medical Center]. The data were collected from October 2018 to March 2020.

The study was approved by the institutional ethics committee at each hospital, and informed consent was obtained from each patient before enrollment and participation in the study.

Subjects and measures

Study subjects were families living with DMD/BMD patients and female carriers of dystrophinopathy receiving medical treatment at the participating hospitals. The diagnosis of DMD/BMD was made by a gene analysis or muscle biopsy. Carriers were diagnosed by a muscular biopsy, gene analysis, or clinical presentations (positive family history and clinical course). Caregivers were selected by an interview survey. When several caregivers provided care for a DMD/BMD patient, we selected the caregiver who had the longest experience as a caregiver. They were all ≥20 years old and able to answer the questionnaires.

The following were administered to those who consented: (1) questionnaires for the caregivers, inquiring about the history, daily living, medical treatment, care status, subjective symptoms (muscle weakness, dyspnea, palpitations, edema), diagnosis of carrier status, and characteristics of the patients with DMD and BMD being cared for; (2) a physical assessment (modified Rankin Scale score, body mass index, manual muscle testing, hypertrophy of the gastrocnemius muscle), blood tests (serum CK, serum BNP), lung function tests, electrocardiograms, and echocardiography for the caregivers; (3) an evaluation of the care burden [Zarit Caregiver Burden Interview (ZBI); including 22 questions, each rated using a 5-point scale (total score range 0-88)] (14) for the current caregivers; and (4) an evaluation of the HRQOL (Short Form 36; SF-36) for the caregivers and non-caregivers with female dystrophinopathy. The SF-36 included 36 questions that are combined into the following eight subdomains: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems, and mental health. In each domain, the scores range from 0 to 100, with higher scores representing a better QOL; a score of 50 is the Japanese general population mean (15,16).

Statistical analyses

Statistical analyses were conducted using the JMP software program, ver. 15.1.0 (SAS Institute, Cary, USA). Pearson's correlation coefficient was calculated for the association between two continuous variables. For group comparisons of ZBI scores, an analysis of covariance was performed with the caregiver age and duration of care as covariates. For other group comparisons, an analysis of variance and chi-square tests were used for continuous and dichotomous variables, respectively. Values of p<0.05 were considered statistically significant.

Results

Subjects

There were 50 subjects, including 36 caregivers (35 women, 1 man) of DMD and BMD patients. Three caregivers had cared for patients in the past. There were 14 non-caregivers with female dystrophinopathy. Twelve (33.3%) of the 36 caregivers had been diagnosed as carriers by a gene analysis and 7 (19.4%) by the clinical course and family history; 14 (38.9%) had not been examined for their carrier status, and 3 (8.3%) were proven to be noncarriers. There were 14 non-caregivers with female dystrophinopathy, of whom 12 were diagnosed by a gene analysis, 1 by a muscle biopsy, and 1 by the clinical course and family history (Table 1).

Table 1.

Study Participants.

Caregivers (n=36)

Diagnosed as carriers (n=19)

Diagnosed by gene analysis (n=12)

Diagnosed by clinical coarse and family history without gene analysis (n=7)

Unexamined possible carriers (n=14)

Proven non-carrier (n=3)

No mutation by gene analysis (n=1)

Unrelated person (n=2)

Non-caregivers with female dystrophinopathy (n=14)

Diagnosed by gene analysis (n=12)

Diagnosed by muscle biopsy (n=1)

Diagnosed by clinical course and family history without gene analysis (n=1)

Characteristics of all caregivers and DMD/BMD patients and the results of the questionnaire

The mean age of all caregivers was 55.7±8.4 (range: 41-74) years old; 28.6% were ≥60 years old. Thirty (83.3%) caregivers were mothers to patients, 1 (2.8%) was a patient's wife, 1 (2.8%) was a patient's grandfather (proven noncarrier), 3 (8.3%) were patients' female siblings, and 1 (2.8%) was a female relative of a patient. The mean duration of care was 15.9±9.5 (range: 1-37) years, with a duration of ≥10 years seen in 75.8%. Sleeping time was ≤6 h in 42.3% of patients. Use of a social work service for care (e.g. visiting medical care and rehabilitation, home nursing care, attending a care center, or staying at a facility for a short time) was reported by 84.3%, and 50% of caregivers were on medical treatment themselves (Table 2). The care recipients were 30 DMD patients (90.9%) and 3 BMD patients (9.1%). Their mean age was 26.9±10.5 (range: 7-55) years old. Thirty patients (90.9%) were not ambulatory. Nine patients (27.2%) did not need respiratory assistance. Twenty patients (60.6%) received non-invasive positive-pressure ventilation, and 4 (12.1%) received tracheostomy positive-pressure ventilation (data not shown).

Table 2.

Characteristics of All Caregivers and Results of the Questionnaire.

		Frequency		Percentage
Sex (n=36)
Female		35		97.2
Age category (n=35)
40-49 years		10		28.6
50-59 years		15		42.9
60-69 years		8		22.9
70-79 years		2		5.7
Relationship to patient (n=36)
Mother		30		83.3
Wife		1		2.8
Grandfather		1		2.8
Sibiling (female)		3		8.3
Relative (female)		1		2.8
Duration of care (n=29)
0-9 years		7		24.1
10-19 years		12		41.4
20-29 years		7		24.1
30-39 years		3		10.3
Sleeping time (n=33)
≤6h		14		42.3
Use of social work service (n=32)		27		84.3
Regular medical checkup of caregiver (n=34)		17		50

Physical assessments and laboratory findings of all caregivers

The modified Rankin Scale scores of caregivers were grade 0 (no symptom) in 55.9%, grade 1 (no significant disability despite symptoms) in 26.5%, grade 2 (slight disability) in 8.8%, grade 3 (moderate disability) in 2.9%, and grade 4 (moderately severe disability) in 2.9%. Nineteen subjects (54.3%) had some symptoms, such as muscle weakness (20%), dyspnea (14.3%), palpitations (25.8%), and edema (8.6%). Seven subjects (20%) had obesity (body mass index ≥25 kg/m²). On a medical examination, 11/31 (31.4%) had muscle weakness on manual muscle testing, and 4/25 (11.4%) had hypertrophy of the gastrocnemius muscle. On blood tests, 21/25 (75%) had elevated serum CK, and 16/24 (66.7%) had elevated serum BNP levels. On lung function tests, 2/19 (10.5%) showed abnormal findings (decreased vital capacity or forced vital capacity). Abnormal findings on electrocardiograms were found in 6 of 27 (17.1%), and abnormal findings on echocardiography (decreased left ventricular ejection fraction) were found in 2/19 (10.5%) (Table 3).

Table 3.

Physical Assessment and Laboratory Findings of All Caregivers.

		Frequency		Percentage
Modified Rankin Scale (n=34)
0		19		55.9
1		9		26.5
2		3		8.8
3		1		2.9
4		1		2.9
Symptom (n=35)
Muscle weakness		7		20
Dyspnea		5		14.3
Palpitation		9		25.8
Edema		3		8.6
Absent		16		45.7
Body mass index ≥25 (n=27)		7		20
Muscle weakness (manual muscle testing, n=31)		11		31.4
Hypertrophy of gastrocnemius muscle (n=25)		4		11.4
Elevated serum CK (n=25)		21		75
Elevated serum BNP (n=24)		16		66.7
Abnormal findings on lung function tests (n=19)		2		10.5
Abnormal findings on electrocardiogram (n=28)		6		17.1
Abnormal findings on electrocardiography (n=19)		2		10.5

CK: creatine kinase, BNP: brain natriuretic peptide

Caregiver burden of current caregivers

The caregiver burden of current caregivers was evaluated by the ZBI, with a higher ZBI score indicating a higher burden. The mean ZBI total score was 20.9±13.1 (range 2-48). Whether the ZBI total score was correlated with various factors was examined. Among caregivers, there were no correlations between the ZBI total score and age (Figure a) or the duration of care (Figure b). There were also no correlations between the ZBI total score and the modified Rankin Scale score ≥2, serum CK level, serum BNP level, subjective symptoms in caregivers, or activities of daily living and ventilator use in the care recipient (data not shown). ZBI total scores adjusted for age and care duration were compared between caregivers diagnosed as carriers (Group I) and caregivers unexamined as carriers (Group II) by using analysis of covariance. There were no significant differences in ZBI total scores between Group I and Group II (Figure c). However, the frequency of a ZBI total score ≥25 (moderate caregiver burden) was significantly higher in Group I than in Group II (Table 4, p=0.04). Caregivers with a ZBI total score ≥25 and those with a ZBI total score <25 had no significant differences in the frequency of a modified Rankin Scale score ≥2, serum CK level, serum BNP level or presence of subjective symptoms in caregivers.

Figure.

Correlation between global ZBI score and age of current caregivers (a) and duration of care (b). We compared ZBI scores adjusted for age and care duration between caregivers diagnosed as carriers (Group I) and caregivers unexamined as carriers (Group II) by using analysis of covariance. Error bars represent 95% confidence interval (c).

Table 4.

Comparison between Caregivers Diagnosed as Carriers and Caregivers Unexamined as Carriers.

	Group I Caregivers diagnosed as carriers	Group II Caregivers unexamined as carriers	p value (I vs. II)
Age	53.8±9.5 (years) (n=18)	58.4±7.0 (years) (n=13)	p=0.14
Duration of care	16.4±9.2 (years) (n=16)	18.2±9.8 (years) (n=9)	p=0.66
Regular medical checkup of caregiver	50% (n=18)	50.0% (n=14)	p=0.50
ZBI total score ≥25 (only current caregivers)	43.8% (n=16)	8.3% (n=12)	p=0.04*
Muscle weakness (subjective symptom)	27.8% (n=18)	14.3% (n=14)	p=0.19
Muscle weakness (manual muscle testing)	33.3% (n=18)	33.3% (n=12)	p=0.65
Elevated serum CK	88.2% (n=17)	60.0% (n=10)	p=0.09
Elevated serum BNP	85.7% (n=14)	44.4% (n=9)	p=0.04*
Abnormal findings on electrocardiography	16.7% (n=12)	0% (n=7)	p=0.25

* p<0.05.

The comparison between caregivers diagnosed as carriers and caregivers unexamined as carriers or proven noncarriers

All caregivers were divided into the following three groups and evaluated: caregivers diagnosed as carriers (Group I), caregivers unexamined as carriers (Group II), and caregivers proven to be noncarriers except for men. Groups I and II showed no significant differences in the age or duration of care. Half of the caregivers in Groups I and II were not receiving medical treatment. The frequencies of elevated serum CK levels were considerably higher in Group I than in Group II, although the difference was not significant (p=0.09). The frequencies of elevated serum BNP levels were significantly higher in Group I than in Group II (p=0.04) (Table 4). Caregivers proven to be noncarriers except for men did not show muscle weakness, elevated serum CK levels, or elevated serum BNP levels (data not shown).

The HRQOL in all caregivers and non-caregivers with female dystrophinopathy

The SF-36 was used to assess the HRQOL. Caregivers (Groups I and II) had slightly lower scores than the Japanese standard scores for physical functioning, role limitations-physical, bodily pain, and social functioning. Female caregivers proven to be noncarriers had higher scores than the Japanese standard scores for all domains. Groups I and II showed no significant differences in the age, frequency of modified Rankin Scale score ≥2, or mean scores for all domains. Non-caregivers with female dystrophinopathy (Group III) had lower scores than the Japanese standard scores for all domains, especially physical functioning (35.3±20.5) and bodily pain (40.6±12.6). We then examined whether or not the HRQOL differed between caregivers diagnosed as carriers and non-caregivers with female dystrophinopathy. The mean ages of Group I (53.8±9.8 years old) and Group III (49.7±15.9 years old) were not markedly different. The frequency of a modified Rankin Scale score ≥2 was significantly higher in Group III (54.6%) than in Group I (10.5%, p=0.001). Physical functioning and role limitations-physical were significantly lower in Group III than in Group I (p<0.05) (Table 5).

Table 5.

Short-form 36 (SF-36) Profile for All Caregivers and Non-caregivers with Female Dystrophinopathy.

	Group I Caregivers diagnosed as carriers (n=19)	Group II Caregivers unexamined as carriers (n=12)	Group III Non-caregivers with female dystrophinopathy (n=11)	p value
Age (years)	53.8±9.8	59.0±6.0	49.7±15.9	p=0.10 (I vs. II), p=0.33 (I vs. III)
Modified Rankin scale ≥2	10.5%	27.2%	54.6%	p=0.24 (I vs. II), p=0.001** (I vs. III)
Physical functioning	47.8±13.3	46.7±15.0	35.3±20.5	p=0.80 (I vs. II), p=0.04* (I vs. III)
Role limitations-physical	47.4±10.4	44.4±14.2	43.1±15.7	p=0.52 (I vs. II), p=0.38 (I vs. III)
Bodily pain	46.1±9.6	41.0±11.4	40.6±12.6	p=0.21 (I vs. II), p=0.19 (I vs. III)
General health perception	48.1±9.6	48.3±9.6	46.1±14.2	p=0.54 (I vs. II), p=0.63 (I vs. III)
Vitality	50.6±9.0	53.1±14.1	45.7±12.9	p=0.21 (I vs. II), p=0.27 (I vs. III)
Social functioning	46.7±8.7	47.4±13.6	44.9±15.7	p=0.46 (I vs. II), p=0.69 (I vs. III)
Role limitations-emotional	51.9±7.9	49.7±15.2	45.2±13.1	p=0.55 (I vs. II), p=0.14 (I vs. III)
Mental health	52.1±7.3	54.1±10.8	49.1±11.7	p=0.10 (I vs. II), p=0.41 (I vs. III)

* p<0.05, ** p<0.01.

Relationship between caregiver burden and the subdomains of the SF-36

In the subdomains of the SF-36, caregivers with a ZBI total score ≥25 showed significantly lower scores in vitality, social functioning, and mental health than those with a ZBI total score <25. However, caregivers with a ZBI total score ≥25 and those with a ZBI total score <25 showed no significant differences in physical functioning, role limitations-physical, bodily pain, general health perception, or role limitations-emotional. Furthermore, the percentage with a mental health score <50 (Japanese general population mean) was significantly higher in Group I (42.1%) than in Group II (8.3%) (p<0.05). The percentage with a vitality and social functioning score <50 showed no significant differences between Groups I and II (data not shown).

Discussion

The present analysis included an assessment of caregivers of DMD and BMD patients in terms of care burden and the HRQOL, as well as other physical aspects of carriers, such as the status of the diagnosis and history of medical checkups, muscular and cardiac symptoms, serum CK and BNP levels, and the cardiac function. Furthermore, undiagnosed carriers and those proven to be noncarriers were compared to better understand the characteristics of caregivers diagnosed as carriers.

In the present study, 34 of 36 (91.7%) caregivers may have been carriers, except for the grandfather of one patient and wife of another, and 13 of 34 (38.2%) caregivers had received genetic testing. Twelve caregivers were diagnosed as carriers by a genetic analysis, and one caregiver showed no mutation. Kobayashi et al. reported that the reasons for fewer gene examinations in Japan are conservative attitudes toward genetic testing and an insufficient explanation of the risk of the onset by clinicians due to a lack of knowledge/information (11). Thus, it has been extremely difficult to conduct clinical studies in this area. This study was performed to stimulate discussion of the problems concerning caregivers who are themselves DMD and BMD carriers.

One important finding from the present study was related to regular medical checkups for caregivers: 50% of caregivers diagnosed as carriers, 47.1% of caregivers with muscle or cardiac symptoms, 52.4% of caregivers with elevated serum CK levels, and 37.5% of caregivers with elevated serum BNP levels were not undergoing regular medical checkups. Adachi et al. reported that regular health checkups for mothers of DMD patients have been performed for 22 years. In that study, cardiomyopathy was observed in 60% of the subjects, including dilated cardiomyopathy-like damage (17). In some reports, the frequency of cardiomyopathy increased with age, even in those with no skeletal muscle symptoms and no cardiac symptoms, as shown in the combined data (4,18,19). The clinical guidelines in Europe and the United States recommend that echocardiography be performed every five years for adult dystrophinopathy carriers (20,21). We also suggest that caregivers of DMD/BMD patients undergo regular medical checkups for the detection of skeletal muscle damage and cardiomyopathy.

Regarding measures of care burden, such as the ZBI, in previous reports, the mean ZBI total scores of DMD caregivers were 29 (22) and 26.3 (23). However, these reports did not refer to caregivers with dystrophin gene mutations. In the present study, the mean ZBI score was 20.9±13.1, ranging from 2 to 48. The mean ZBI total score did not differ significantly between caregivers diagnosed as carriers (Group I) and caregivers unexamined as carriers (Group II). However, the percentage of caregivers with a ZBI total score ≥25 and a score <50 on the mental health subdomain of the SF-36 was significantly higher in Group I than in Group II. Of the 22 questions on the ZBI, “Feel that your relative is dependent on you” (Nearly always or Quite frequently: 58%) was rated the highest, followed by “Are afraid of what the future holds for your relative” (Nearly always or Quite frequently: 26%). Interestingly, despite the difference in the nationality and race of the study participants, Landfeldt et al. also demonstrated that the same questions were frequently rated with “Nearly always or Quite frequently” in their study as well (22). Furthermore, several studies have demonstrated that caregivers of DMD patients are more likely to have anxiety and depression than the general population (12,22,24,25). Responses to the questions might show a tendency toward greater anxiety about the future and the dependence of the cared-for patient than about one's own health management. These findings suggest that mental health and psychosocial support are important to provide for caregivers of DMD/BMD patients (especially those diagnosed as carriers) in order for them to maintain their QOL and the ability to provide long-term care.

Previous studies have examined the HRQOL of DMD caregivers using the World Health Organization Quality of Life instrument (WHOQOL-BREF) (23), EuroQOL 5 dimensions 3-level (EQ-5D-3 L) (22,24,26), Short Form-12 Health Survey (22), and Carer Quality of Life measurement (24). In the present study, the SF-36 was selected because it is an internationally recognized questionnaire that allows for the comprehensive assessment of the HRQOL. The caregivers diagnosed as carriers (Group I) and caregivers unexamined as carriers (Group II) had slightly lower scores than the national standard values for physical functioning, role limitations-physical, bodily pain, and social functioning. In contrast, the HRQOL of caregivers proven to be noncarriers was maintained for all domains. The low physical QOL scores in Groups I and II, who were definite or possible carriers, may be attributed to muscle weakness and elevated levels of serum CK and BNP. A comparison of the HRQOL between Groups I and III showed that Group III had a significantly lower physical and mental QOL. This difference may be attributed to the fact that, compared with Group I, those in Group III had significantly reduced activities of daily living due to disease progression and consequent reduction in muscular strength. This result shows that caregivers diagnosed as carriers may experience worsening muscle symptoms and a reduction in activities of daily living over time, which can consequently result in an overall reduction in the HRQOL.

Several limitations associated with the present study warrant mention. First, the number of subjects was limited, despite it being a multicenter investigation. The reasons for the limited number of subjects may be that 1) participation in a study of genetic diseases can lead to mental distress, and 2) it is difficult to obtain informed consent from individuals with mental or intellectual disabilities, as well as those with mild disease who do not feel the need to participate in the study. Thus, the present study subjects may not be representative of all caregivers of DMD/BMD patients. Second, a comparison with caregivers proven to be noncarriers would be needed to identify challenges that are specific to caregivers who are carriers. However, it was not possible to make such a comparison because there were only two caregivers proven to be noncarriers (except for men) in the present study. Instead, the comparison group included carriers who had not been diagnosed; however, these undiagnosed individuals may include carriers who never underwent genetic testing. Thus, the data should be interpreted carefully. Third, given the various tests that were included in the study (questionnaire, physical examination, burden assessment, HRQOL), there were some missing data, since some subjects were unable to visit the hospital multiple times. A large-scale, prospective, cohort study with multiple institutions and a larger sample size is needed to validate the present findings in the future. In particular, since studies of ethical and social issues are challenging to perform in Japan, it is important to establish a support system to reduce the psychological burden of study subjects and select appropriate clinical examinations and study-related metrics.

Conclusion

Some caregivers of DMD/BMD patients may themselves have muscular or cardiac symptoms and thus a particularly heavy care burden. It is therefore necessary for these individuals, especially female carrier caregivers, to receive regular health checkups and appropriate health management. Medical professionals should make these findings known to not only patients and caregivers but also other professionals in the hopes of promoting a better understanding of the health management of caregivers, which may make it easier for patients living at home to receive better support.

We are confident that the present findings will contribute to discussing the health management of caregivers of dystrophinopathy patients.

The authors state that they have no Conflict of Interest (COI).

Financial Support

This study was supported by a research grant from the Ministry of Health, Labour and Welfare (MHLW) for “Research and Study for the Dissemination of Standard Medical Care for Muscular Dystrophy (H30-Nanchitou (Nan)-Ippan-005)” program.