Diagnosis Of Duchenne Muscular Dystrophy Research Articles

Current management of Duchenne muscular dystrophy in the Middle East: expert report.

Aim:Duchenne muscular dystrophy (DMD) is a severe and rare X-linked neuromuscular childhood disorder that results in functional decline, loss of ambulation and early death due to cardiac or respiratory failure. The objective of this paper is to address different aspects of the current management of DMD in the Middle East, north Africa (MENA) region, and to gather experts’ recommendations on how to optimally diagnose and treat patients suffering from this disease.Methods:A group of experts (neuromuscular medicine, neuropediatricians and geneticists) convened to discuss the diagnosis and management of DMD in the MENA region. A list of practical statements was prepared by the chair of the meeting to guide the discussions around critical aspects relating to the current and future management of DMD.Results & conclusion:Ideally, DMD management should be a multidisciplinary approach. Nevertheless, few tertiary care hospitals in the region are currently able to provide the full spectrum of medical expertise and services needed by DMD patients. Clinical practice in the region remains heterogeneous. Specific guidelines for diagnosis and treatment are needed in the MENA region to improve outcomes. Disease awareness among the general public and the medical community is lacking. Now that mutation-specific therapies are being developed and more widely studied, general education programs regarding early signs and symptoms, a standardized referral and diagnosis pathway, patient registries and support groups will significantly improve the management of the disease.

Fatigue in young people with Duchenne muscular dystrophy.

To describe fatigue in Duchenne muscular dystrophy (DMD) from patients' and parents' perspectives and to explore risk factors for fatigue in children and adolescents with DMD. A multicentre, cross-sectional study design was used. Seventy-one patients (all males; median age 12y, age range 5-17y) identified via the Canadian Neuromuscular Disease Registry, and their parents completed questionnaires. Subjective fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale by child self-report and parent proxy-report. Patients with DMD across ages and disease stages experienced greater fatigue compared to typically developing controls from published data. Sleep disturbance symptoms were associated with greater fatigue by child self-report (ρ=-0.42; p=0.003) and parent proxy-report (ρ=-0.51; p<0.001). Depressive symptoms were associated with greater fatigue by child self-report (ρ=-0.46; p<0.001) and parent proxy-report (ρ=-0.45; p<0.001). Lower functional ability was associated with greater fatigue by parent proxy-report (ρ=0.26; p=0.03). Physical activity level, and musculoskeletal, respiratory, and cardiac function were not associated with fatigue. In paediatric DMD, sleep disturbance symptoms and depressive symptoms are potentially modifiable factors associated with fatigue, warranting additional investigation to facilitate the development of therapeutic strategies to reduce fatigue. Fatigue is a major issue in paediatric Duchenne muscular dystrophy (DMD) across ages and disease stages. Sleep disturbance and depressive symptoms are significantly associated with fatigue in paediatric DMD.

Targeted sequencing of the DMD locus: A comprehensive diagnostic tool for all mutations.

Background & objectives:Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the DMD gene. Diagnosis of DMD has been a challenge as the mutations in the DMD gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the DMD gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies.Methods:The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the DMD gene to identify the nature of the mutation.Results:In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the DMD gene.Interpretation & conclusions:Our findings showed the importance of NGS in the routine diagnostic practice in the identification of DMD mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the DMD gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.

Evidence-Based Consensus and Systematic Review on Reducing the Time to Diagnosis of Duchenne Muscular Dystrophy

Evidence-Based Consensus and Systematic Review on Reducing the Time to Diagnosis of Duchenne Muscular Dystrophy

Cross-section and feasibility study on the non-invasive evaluation of muscle hemodynamic responses in Duchenne muscular dystrophy by using a near-infrared diffuse optical technique.

Duchenne muscular dystrophy (DMD) is an X-linked debilitating muscular disease that may decrease nitric oxide (NO) production and lead to functional muscular ischemia. Currently, the 6-minute walk test (6-MWT) and the North Star Ambulatory Assessment (NSAA) are the primary outcome measures in clinical trials, but they are severely limited by the subjective consciousness and mood of patients, and can only be used in older and ambulatory boys. This study proposed using functional near-infrared spectroscopy (fNIRS) to evaluate the dynamic changes in muscle hemodynamic responses (gastrocnemius and forearm muscle) during a 6-MWT and a venous occlusion test (VOT), respectively. Muscle oxygenation of the forearm was evaluated non-invasively before, during and after VOT in all participants (included 30 DMD patients and 30 age-matched healthy controls), while dynamic muscle oxygenation of gastrocnemius muscle during 6-MWT was determined in ambulatory participants (n = 18) and healthy controls (n = 30). The results reveal that impaired muscle oxygenation was observed during 6-MWT in DMD patients that may explain why the DMD patients walked shorter distances than healthy controls. Moreover, the results of VOT implied that worsening muscle function was associated with a lower supply of muscle oxygenation and may provide useful information on the relationship between muscular oxygen consumption and supply for the clinical diagnosis of DMD. Therefore, the method of fNIRS with VOT possesses great potential in future evaluations of DMD patients that implies a good feasibility for clinical application such as for monitoring disease severity of DMD.

DUCHENNE MUSCULAR DYSTROPHY - GENETICS: P.216Genetic carrier screening for Duchenne muscular dystrophy: the outcome of over forty years of genetic counselling on disease incidence in New South Wales Australia

Duchenne muscular dystrophy (DMD), an X-linked recessive genetic disorder results in progressive muscle weakness, causing significant morbidity and mortality. Its incidence is approximately 1 in 5000 live male births. DMD is caused by mutations in the dystrophin gene, maternally inherited in approximately two thirds of affected boys. Female relatives have carrier risk. Clinical genetics services offer carrier testing ('cascade screening') and genetic counselling for relatives of DMD patients, enabling identification of carrier status and provision of reproductive options. In selected countries, reduced disease incidence is observed, possibly due to genetic counselling, cascade testing and prenatal diagnosis. To estimate changes in DMD incidence in NSW over 40 years and determine whether cascade screening and genetic counselling has led to this change. A retrospective study of 'probands' (live male and prenatal genetically diagnosed DMD) cases born within NSW from 2002-2012 will be conducted. Female carriers/mosaic cases are excluded from analysis. A retrospective clinical review of confounding factors potentially associated with DMD diagnosis will also be conducted, using clinical data sourced from all the major NSW paediatric hospitals. Data will be collated with results from a previous study reporting DMD incidence over a 25-year period from 1975 to 2001 inclusive. The combined results of these studies will be presented in the final analysis. Birth rate statistics will be sourced from the Australian Bureau of Statistics. The denominator for incidence will be live male birth rates. Data analysis is pending. However, we hypothesize that DMD incidence in NSW has reduced over the last 40 years owing to improvements in the methodology of genetic screening. This study will demonstrate the impact of robust genetic screening and counselling services, thus serving as a model for other health care systems globally.

Gestational Outcomes of Pregnant Women Who Have Had Invasive Prenatal Testing for the Prenatal Diagnosis of Duchenne Muscular Dystrophy

Aim To show the importance of prenatal diagnosis of Duchenne Muscular Dystrophy (DMD) and to demonstrate the effect of DMD gene mutations on gestational outcomes. Materials and Methods We retrospectively evaluated 89 pregnancies in 81 individuals who were referred to Hacettepe University for prenatal diagnosis of DMD between January 2000 and December 2015. Prenatal diagnostic methods (chorionic villus sampling (CVS): 66, amniocentesis (AC): 23) were compared for test results, demographic features, and obstetric outcomes of pregnancies. The female fetuses were divided into two groups according to the DMD status (healthy or carrier) to understand the effect of DMD gene mutations on obstetric outcomes. Results Eight prenatally diagnosed disease-positive fetuses were terminated. There was no statistically significant difference between the CVS and AC groups in terms of study variables. There were 46 male fetuses (51.6%) and 43 female fetuses (48.4%). Fifteen of the female fetuses were carriers (34.8%). Median birthweight values were statistically insignificantly lower in the carrier group. Conclusion Pregnancies at risk for DMD should be prenatally tested to prevent the effect of disease on families and DMD carrier fetuses had obstetric outcomes similar to DMD negative female fetuses.

A resolved discrepancy between multiplex PCR and multiplex ligation-dependent probe amplification by targeted next-generation sequencing discloses a novel partial exonic deletion in the Duchenne muscular dystrophy gene.

The genetic diagnosis of Duchenne muscular dystrophy (DMD) has been complicated by the large size of the gene and its heterogeneous mutational spectrum. Multiplex PCR and multiplex ligation-dependent probe amplification (MLPA) are two well-established mutation screening methods. Here, we applied targeted next-generation sequencing (NGS) to clarify discrepant results between multiplex PCR and MLPA in a Chinese patient with DMD. MLPA was performed to confirm multiplex PCR results obtained previously. Targeted NGS was then used to analyze the full-length DMD gene including introns. Multiplex PCR had previously identified an apparent deletion of exon 43 in the patient with DMD, but current MLPA indicated that exon 43 was present. Targeted NGS to clarify the genetic diagnosis identified a novel mutation, c.6241_c.6290+1109del1159insAC, which caused partial deletion of exon 43. This mutation removed the annealing sequence of the exon 43 reverse primer in multiplex PCR but had no influence on the hybridization site of the MLPA probe. Therefore, the discrepancy between the two methods was caused by partial exonic deletion that escaped MLPA detection. Targeted NGS disclosed a novel partial exonic deletion in the DMD gene as the cause of discrepancy between multiplex PCR and MLPA. Targeted NGS could be used to provide a more accurate genetic diagnosis of DMD, particularly in cases of partial exonic deletions, which will be of benefit in patient management and the identification of disease carriers.

Is There a Delay in Diagnosis of Duchenne Muscular Dystrophy Among Preterm-Born Males?

The objective of this study was to investigate whether males who were born preterm took longer to receive a Duchenne muscular dystrophy diagnosis than term males. Data for males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using a Kaplan-Meier estimator. The first signs and symptoms were noted at a median age of 2 years in both groups. Median age when first signs and symptoms prompted medical evaluation was 2.59 years among preterm and 4.01 years among term males. Median age at definitive diagnosis was 4.25 years and 4.92 years for preterm and term males, respectively. Neither difference was statistically significant. Preterm males tended to be seen for their initial medical evaluation earlier than term males, though they were not diagnosed significantly earlier. It may take clinicians longer after the initial evaluation of preterm males to arrive at a Duchenne muscular dystrophy diagnosis.

Skin cells for use in an alternate diagnostic method for Duchenne muscular dystrophy

The importance of molecular diagnosis and identification of disease-associated variants for Duchenne muscular dystrophy (DMD) is evident in the age of gene-based therapies and personalised medicine. Detection of the causative DMD variant and determination of its effects on dystrophin expression is best achieved by analysis of RNA extracted from muscle biopsy material. However, this is not done routinely, as the procedure can be traumatic, especially to young children, and carries risk of complications related to the use of anaesthetic. As skin biopsies are safer and straightforward to perform than muscle biopsies, we investigated the utility of cultured human epidermal melanocytes and dermal fibroblasts as alternative tools for RNA-based diagnosis of DMD. Shallow skin biopsies from 5 boys with genetically confirmed diagnoses of DMD were used to culture fibroblasts and melanocytes. Biopsies were sampled, and tolerated without complications, using local anaesthetic cream. Dystrophin expression in the cultured cells was assessed using immunocytochemical staining, quantitative real-time PCR and cDNA sequencing methodologies. We observed differential expression of the full-length dystrophin muscle transcript, with significantly more robust expression in melanocytes, compared to that in fibroblasts. Our results suggest that cultured skin melanocytes may present an alternative tool for RNA-based genetic diagnosis of DMD.

COGNITIVE FUNCTIONING AND AUTONOMY OF PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY

Cognitive problems and a deepening dependence on one’s immediate environment inherently accompany Duchenne Muscular Dystrophy (DMD). The disease is progressive, and the size of the dystrophin gene determines the extraordinary complexity of the causes of this disease at the genetic and molecular level. The aim of the study was to characterize the cognitive problems and the extent of independence of patients with genetically confirmed DMD. An attempt was also made to reconstruct the patient's life history in three periods: before the appearance of the first symptoms, during the search for a diagnosis and after confirming the diagnosis of DMD. The study group consisted of male patients between 10 and 13 years of age (N = 14). The Diagnosis of Cognitive Functions Battery - PU1 and an experimental tool for studying autonomy were used. Information on the condition of the attention, memory and executive functions of patients was obtained. The study of autonomy measurably supplemented knowledge in terms of the degree of the patients’ dependence on the environment with regard to everyday functioning. The best functioning component of attention in the examined patients is orientation (o) (13 patients achieved average results in this aspect). Selectivity (s) turned out to be the weakest component, as only five patients obtained average results (the others obtained low results) in this aspect. Autonomy results (AU) indicate group diversity and inter-subject variability in the disease progression (subjects scored from 6 to 47 points). The clinical picture of the disease is not homogeneous. Patients, despite their similar age, differ in the progression of the disease and the resulting effects. This induces the need for an individual approach to each patient and the preparation of a unique set of therapeutic interactions for each of them.

Muscular Dystrophy: A Retrospective Evaluation of 15 Cases.

Objectives:The aim of this study was to investigate the clinical and laboratory findings of patients followed up with a diagnosis of Duchenne muscular dystrophy (DMD).Methods:This retrospective study included 15 boys diagnosed with muscular dystrophy at the Pediatric Neurology Department between July 2008 and July 2016. The presenting symptoms; level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK); ophthalmological findings; echocardiography (ECHO) results; findings on brain magnetic resonance imaging (MRI); genetic analysis results; and muscular biopsy findings were evaluated.Results:The mean age of the patients was 5.2±2.3 years (range: 11 months-8 years) and the mean age at the onset of DMD was 4.1±2.2 years (range: 10 months-6 years). The ALT level ranged between 67 and 527 IU/L, the AST between 44 and 455 IU/L, and the CK between 931 and 19,595 IU/L. The genetic analysis determined deletions in 12 (80%) and duplications in 2 (13%) patients.Conclusion:Parents with a DMD-affected child should be provided with genetic counseling in order to make decisions about future pregnancies.

Early Diagnosis and Treatment – The Use of Ataluren in the Effective Management of Duchenne Muscular Dystrophy

The understanding of the natural history of Duchenne muscular dystrophy (DMD) is increasing rapidly and new treatments are emerging that have the potential to substantially improve the prognosis for patients with this disabling and life-shortening disease. For many, however, there is a long delay between the appearance of symptoms and DMD diagnosis, which reduces the possibility of successful treatment. DMD results from mutations in the large dystrophin gene of which one-third are de novo mutations and two-thirds are inherited from a female carrier. Roughly 75% of mutations are large rearrangements and 25% are point mutations. Certain deletions and nonsense mutations can be treated whereas many other mutations cannot currently be treated. This emphasises the need for early genetic testing to identify the mutation, guide treatment and inform genetic counselling. Treatments for DMD include corticosteroids and more recently, ataluren has been approved in Europe, the first disease-modifying therapy for treating DMD caused by nonsense mutations. The use of ataluren in DMD is supported by positive results from phase IIb and phase III studies in which the treatment produced marked improvements in the 6-minute walk test, timed function tests such as the 10 m walk/run test and the 4-stair ascent/descent test compared with placebo. In these trials, ataluren was well tolerated and adverse event profiles were similar to placebo. As such disease-modifying treatments become more widely available, the outlook for children with DMD will improve but physicians must be aware of the disease, rapidly initiate testing where it is suspected and promptly begin appropriate treatment.

Next Generation Sequencing approach to molecular diagnosis of Duchenne muscular dystrophy; identification of a novel mutation

Duchenne Muscular Dystrophy (DMD; MIM 310200) is one of the most common and severe type of hereditary muscular dystrophies. The disease is caused by mutations in the dystrophin gene. The dystrophin gene is associated with X-linked recessive Duchenne and Becker muscular dystrophy. This disease occurs almost exclusively in males. The clinical symptoms of muscle weakness usually begin at childhood. The main symptoms of this disorder are gradually muscular weakness. The affected patients have inability to standing up and walking. Death is usually due to respiratory infection or cardiomyopathy. In this article, we have reported the discovery of a new nonsense mutation that creates abnormal stop codon in the dystrophin gene. This mutation was detected using Next Generation Sequencing (NGS) technique. The subject was a 17-year-old male with muscular dystrophy that who was suspected of having DMD. He was referred to Hakim medical genetics center of Neyshabur, IRAN.

Evaluation of cardiac functions in children with Duchenne Muscular Dystrophy: A prospective case-control study.

BackgroundDuchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. The incidence of cardiomyopathy in DMD increases with age, so its early detection is important because institution of cardioprotective medical therapies may slow adverse remodeling and attenuate heart failure symptoms in these patients.ObjectiveTo assess the cardiac functions in children clinically suspected to have DMD.MethodsOver a one-year period, 28 male children aged from 3 to 18 years old, who met the criteria for diagnosis of DMD compared to 47 healthy controls children, were approached to participate in the study. The included children were subjected to full clinical examination, and blood samples were collected to determine creatinine phosphokinase (CPK), troponin I enzyme, myoglobin and lactate dehydrogenase (LDH) enzyme level. Echocardiography and 12-leads electrocardiogram (ECG) were also done for children in both groups. Data were analyzed using Independent-samples t-test, Mann-Whitney U, Chi square, and Fisher’s exact test.ResultsThe mean age of the cases group was 7.29±3.24 years versus 8.06±2.86 years for controls. In DMD group, 25% had positive family history of DMD while 35.7% of them had positive consanguinity. All cases had elevated CPK level while CPK level in controls was normal (p<0.0001). LDH level was elevated in 19 cases (67.86%) of DMD while all controls children had normal LDH level (p<0.0001). Furthermore, the mean serum myoglobin level of DMD patients was higher relative to that of healthy controls (39.39±7.25 versus 33.68 ±12.38 ng/ml respectively) (p=0.01). Echocardiography of our patients revealed that seven cases (25%) had low ejection fraction (EF) and fraction shortening (FS). In addition, all controls children had normal EF (p<0.0001) and normal FS (p<0.0001). Interestingly, ECG showed that 28.57% of cases had sinus tachycardia vs. 6.88% for controls (p=0.0001). Prolonged QTc interval was present in 39.29% of cases (mean 431.39±43.60) while all controls had normal QTc duration for age (mean of 415.17±25.2) (p<0.0001).ConclusionECG manifestations in children with DMD in the form of sinus tachycardia and prolonged QTc interval are an early alarm for developing cardiomyopathy before overt echocardiographic findings appear.

Duchenne muscular dystrophy: A immunohistochemical profile and deletion pattern in dystrophin gene in North Indian population

Background: Duchenne muscular dystrophy (DMD), one of the most common X linked muscular disorder, affecting 1 in 3500 male births and is caused by mutation in dystrophin gene. 65% of DMD cases are caused by large deletion of dystrophin gene, followed by duplication (5-10%) or point mutation (25-30%). There is wide mutation spectrum of the mutations in dystrophin gene. Hence, population specific information is needed on mutation spectrum and frequency of common mutations occurring in that particular population for appropriate counseling, prenatal diagnosis and for developing genetic therapy in future. Aims and Objectives: To find out the frequency and distribution of deletion in dystrophin gene in DMD patients along with contribution of pathology and genetic testing in diagnosis of DMD and Becker muscular dystrophy (BMD) in North Indian population.Materials and Methods: Dystrophin gene was screened for deletion by multiplex polymerase chain reaction (PCR). Out of 41 patients, 09 patients underwent muscle biopsy, on which immunohistochemistry was performed for dystrophin, sarcoglycan, dysferlin and merosin.Results: Majority of the deletions were located in distal hotspot region (26/39 ~66.66%) which includes the exons 45-55 and 15.38% of deletions were located at the proximal hotspot region (2- 19 exons).Conclusion: In the present study, 34% patients only showed deletion. Hence complete work up of any muscular dystrophy requires immnohistochemical analysis to see the expression of muscle proteins along with multipleplex PCR test to detect any exon deletion, multiplex ligation-dependent probe amplification (MLPA) to detect point mutation and duplication and western blotting to quantify the dystrophin protein.Asian Journal of Medical Sciences Vol.8(6) 2017 13-18

AB095. Prenatal diagnosis of Duchenne muscular dystrophy by combining of multiplex Polymerase Chain Reaction and Multiplex Ligation dependent Probe Amplification

AB095. Prenatal diagnosis of Duchenne muscular dystrophy by combining of multiplex Polymerase Chain Reaction and Multiplex Ligation dependent Probe Amplification

The natural history of the patients with Duchenne muscular dystrophy in Taiwan: A medical center experience

Duchenne muscular dystrophy (DMD) is the most common hereditary muscular dystrophy and caused by DMD gene mutation. In addition to progressive proximal muscle weakness, respiratory, orthopedic, and gastrointestinal complications are often observed in DMD. The natural history of patients with DMD in Taiwan has not been reported thus far. Medical records of 39 patients who received a diagnosis of DMD between 1999 and 2016 at Kaohsiung Medical University Hospital were reviewed. The diagnosis of DMD was confirmed through muscle biopsy or DMD genetic analysis. The mean onset age and mean follow-up period were 2.75 years and 6.76 years, respectively. Seventeen patients (43.5%) had a family history of DMD. The mean full intelligence quotient of the patients was 71.08, and the mean age of walking ability loss was 9.7 years (25 patients). The mean onset age of respiratory insufficiency was 10.64 years with a decline rate of 5.18% per year (25 patients). The mean onset age of cardiomyopathy was 14.69 years (seven patients). The mean onset age of scoliosis was 13.29 years with a progression rate of 11.48° per year (14 patients). Eleven (28.2%) and eight (20.5%) patients had deletions and duplications of DMD, respectively. Fourteen patients (35.9%) had point mutations or small deletions or insertions. Five patients received only multiplex ligation-dependent probe amplification (MLPA) analysis and exhibited neither deletion nor duplication. No mutation was identified in one patient through both MLPA and exon sequencing. The clinical phenotypes and disease course in our cohort were consistent with that reported in previous studies. However, the proportion of point mutations or small deletions or insertions in our study was considerably higher than that in reports from other populations. Cardiac ejection fraction was found not a reliable biomarker for identifying cardiac problems, discovering a better parameter is necessary.

Parents' Reactions to the Diagnosis of Duchenne Muscular Dystrophy: Associations Between Resolution, Family Functioning, and Child Behavior Problems.

Duchenne muscular dystrophy (DMD) is the most frequent inherited form of muscular dystrophy during childhood. DMD is a severe and progressive disease. Children initially have no symptoms, but the diagnosis is often delayed until the child is about 5 years old. Although few studies have addressed parent reactions to DMD, parental reactions to other serious childhood conditions have been documented. This study aims to understand the resolution styles that parents use in the context of their children with DMD. Data were collected on 39 parents residing in central Italy, comprising 23 mothers and 16 fathers of children with DMD of a mean age of 12 years. The participants attended a single assessment session lasting 60-80 minutes in which they were interviewed and completed the questionnaire. The participants completed the Reaction to Diagnosis Interview, which is composed of five open-ended questions about parents' memories, thoughts, and feelings about their child's diagnosis. The interviews were videotaped, transcribed, and coded. The Reaction to Diagnosis Interview classifies parents into two main classifications: "resolved" and "unresolved." In addition, the participants responded to questions about their perceptions of family functioning and about the behavioral problems of their children. A hierarchical multiple regression analysis was used to examine the role of child characteristics, disease severity, resolution classification (yes/no), and family variables as predictors of child behavior problems. The proportion of the resolved cases found in this study (41%) was lower than the mean proportion of resolved cases (60%) found in previous studies. Within the resolved category, "thinking oriented" was the most prevalent subcategory. Resolved participants reported significantly higher scores for family functioning and family satisfaction than unresolved participants. No differences were found between the groups in terms of perceptions of family communication. The hierarchical multiple regression analysis showed that a lower level of family functioning was the strongest predictor of child behavior problems. Having a higher level of disease severity and being unresolved were also identified as predictors of child behavior problems. Results highlight the relevance of parent resolution in the adjustment process of children. The findings of this study may assist professionals in the medical field to focus on family variables and the parent process of diagnosis resolution as the primary goals in the prevention of child behavior problems.

A comparative study of care practices for young boys with Duchenne muscular dystrophy between Japan and European countries: Implications of early diagnosis

Early diagnosis of Duchenne muscular dystrophy (DMD) is widely advocated to initiate proactive interventions and genetic counselling. Genetic testing now allows the diagnosis of DMD even prior to the onset of symptoms. However, little is known about care practices and their impact on young DMD boys and families after receiving an early diagnosis. We analysed 64 young boys (Japan, 19; the United Kingdom, 10; Germany, 18; Hungary, 6; Poland, 5; and the Czech Republic, 6) aged <5 years and diagnosed at ≤2 years old among the participants of the cross-sectional study about care practice in DMD. A combination of elevated serum creatine kinase and genetic testing usually led to the diagnosis (n = 31, 48%); 41 boys visited neuromuscular clinics more than once a year. Early diagnosis did not generally result in higher satisfaction among DMD families, and country-specific differences were observed. Psychosocial support following early diagnosis was perceived as insufficient in most countries, and deficits in access and uptake of genetic counselling resulted in lower satisfaction in the Japanese cohort. In conclusion, seamless and comprehensive support for DMD families following early diagnosis at presymptomatic stages should be taken into consideration if early genetic testing or newborn screening is made available more widely.