Orphanet Journal of Rare Diseases | Survey on Diagnostic Pathways and Care Status of CMT Patients in Germany

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This study reveals that German patients with Charcot-Marie-Tooth disease experience an average diagnostic delay of 13.7 years before receiving a confirmed diagnosis, and more than half have been misdiagnosed, highlighting the urgent need to optimize rare disease diagnostic and care pathways.

 

Literature Overview

The article 'Patient journey with Charcot-Marie-Tooth Disease – A German patient survey study,' published in Orphanet Journal of Rare Diseases, reviews and summarizes the prolonged journey from symptom onset to diagnosis among German patients with Charcot-Marie-Tooth (CMT) disease, along with their current care status. By surveying 270 CMT patients via questionnaire, the study systematically analyzes key issues such as diagnostic delays, misdiagnosis rates, healthcare-seeking pathways, and psychological burden. Results show an average of 13.7 years from symptom onset to diagnosis, nearly half of patients underwent hospitalization for evaluation, and over half were previously misdiagnosed, leading to inappropriate treatment and health damage. The study further indicates that patients whose first consultation was with neurology or genetics specialists received faster diagnoses, whereas initial orthopedic consultations significantly prolonged the diagnostic timeline. This research provides crucial empirical support for improving early diagnostic strategies for CMT and other hereditary neuropathies.

Background Knowledge

Charcot-Marie-Tooth disease (CMT) is a group of autosomal dominant or X-linked inherited peripheral neuropathies and one of the most common hereditary neuromuscular disorders, with a global prevalence of approximately 1 in 2,500. CMT is primarily characterized by progressive distal muscle weakness, sensory loss, and foot deformities, typically manifesting in childhood or adolescence. Although CMT has traditionally been considered incurable, targeted gene therapies and disease-modifying treatments have recently entered clinical trials, underscoring the importance of early diagnosis. However, due to nonspecific symptoms and slow progression, CMT is frequently misdiagnosed as other neurological or orthopedic conditions, resulting in prolonged underdiagnosis or misdiagnosis. Currently, there is a lack of systematic, patient-centered quantitative studies globally, and even in countries with well-developed healthcare systems like Germany, significant diagnostic barriers remain. This study fills that gap by revealing structural issues such as uneven distribution of medical resources, low accessibility to specialists, and insufficient cross-disciplinary awareness, providing practical evidence for developing more efficient rare disease diagnostic pathways. Additionally, the study emphasizes the potential of digital health tools in enhancing patient education and remote management, offering direction for future integration of intelligent support systems.

 

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Research Methods and Experiments

This study employed a cross-sectional survey design, conducted via the REDCap electronic data capture platform at the CMT outpatient clinic of Charité University Medicine Berlin and through the German Society for Muscular Diseases (DGM). The 23-item questionnaire covered demographics, symptom onset, initial diagnosis experiences, diagnostic processes, history of misdiagnosis, quality of care, and attitudes toward digital healthcare. The survey period spanned from October 1, 2024, to April 1, 2025, collecting 270 valid responses—81 from the CMT specialty clinic and the remainder from patient advocacy organizations. Inclusion criteria required patients to have a genetically confirmed diagnosis of CMT or HSMN; those with nonspecific 'peripheral neuropathy' or undetermined diagnoses were excluded. Data analysis was performed using GraphPad Prism 10.5.0, applying descriptive statistics, Mann-Whitney U tests, and Kruskal-Wallis tests for intergroup comparisons, with stratified analyses based on age, gender, and initial specialty.

Key Findings and Insights

• The average time from symptom onset to first medical consultation was 5.2 years, while the time to definitive diagnosis reached 13.7 years, indicating widespread delays in both seeking care and receiving diagnosis
• 40% of patients first consulted neurologists, but 24% initially visited orthopedists, who exhibited significantly longer diagnostic delays (median delay of 4 years), suggesting inadequate CMT recognition among orthopedic physicians
• 51.9% of patients had been misdiagnosed; among them, 29.6% received incorrect treatments, and 61.3% believed these treatments caused permanent health damage
• 30% of patients were hospitalized for diagnostic purposes, and 15.9% were hospitalized multiple times; complex neurophysiological tests, lumbar punctures, and MRIs were frequently reported as painful or distressing procedures
• Only 35.2% of patients felt 'reassured' or 'somewhat reassured' after diagnosis, while over half reported feeling 'unsure' or 'very confused,' reflecting a critical need for improved diagnostic communication
• Younger generations (born after 1995) experienced significantly shorter diagnostic delays than older generations, indicating improved diagnostic awareness in recent years
• 84.6% of patients received symptomatic treatments such as physical therapy or orthotics, but only 15% were offered regular follow-ups, indicating that long-term management remains inconsistent
• 93% of patients expressed a strong need for reliable disease information, and 78.9% were willing to use digital tools (e.g., apps or telemedicine), with acceptance unaffected by age

Implications and Future Directions

This study is the first to systematically map the diagnostic journey of CMT patients in Germany, revealing an average delay of over 13 years from symptom onset to diagnosis—far exceeding that of most other rare diseases. This prolonged delay not only increases patients' psychological burden but also leads to incorrect treatments and permanent functional impairments, making early diagnosis especially critical as disease-modifying therapies emerge. The findings emphasize the need to strengthen primary care and orthopedic physicians’ ability to recognize CMT and promote standardized referral pathways to reduce misdiagnosis risks.

Moreover, the study found high openness among patients toward digital health tools, suggesting that remote monitoring, shared electronic health records, and AI-assisted preliminary screening systems could become key instruments for improving rare disease management. It is recommended to develop integrated digital platforms that combine genetic testing guidance, symptom tracking, and expert consultation to shorten diagnostic timelines. Additionally, training in physician-patient communication should be enhanced to ensure diagnostic disclosure includes sufficient educational support, thereby reducing patient anxiety.

 

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Conclusion

Through a questionnaire survey of 270 German CMT patients, this study systematically reveals significant delays and structural barriers in their diagnostic and care pathways. An average diagnostic delay of 13.7 years, a misdiagnosis rate exceeding 50%, and widespread psychological distress highlight the inadequacies of the current healthcare system in managing hereditary neuromuscular disorders. The initial specialty significantly impacts diagnostic efficiency—neurology and genetics consultations accelerate diagnosis, whereas orthopedic first visits substantially prolong the process, indicating a need to increase CMT awareness among non-neurological physicians. As disease-modifying therapies enter clinical trials, early diagnosis will become a critical prerequisite for successful treatment. Therefore, there is an urgent need to establish multidisciplinary collaboration networks, promote standardized diagnostic pathways, and integrate digital health tools to improve patient accessibility and management efficiency. This study provides empirical foundations for optimizing the care ecosystem for CMT and other rare diseases, offering clear directions for policymakers and clinical institutions. Future efforts should expand research to multinational cohorts to validate the effectiveness of interventions and advance the rare disease vision of 'no more diagnostic odysseys.'

 

Helena F Pernice, Susann May, Felix Mühlensiepen, Agata Mossakowski, and Katrin Hahn. Patient journey with Charcot-Marie-Tooth Disease – A German patient survey study. Orphanet Journal of Rare Diseases.