Undiganosed rare genetic diseases when managing neuropsychiatric symptoms: A systematic review of case literature
Clinical Genetics and Therapeutics
-
Primary Categories:
- Health services and Implementation
-
Secondary Categories:
- Health services and Implementation
Introduction:
Individuals affected by rare genetic diseases can face debilitating diagnostic challenges when mental health symptoms are present. Accumulating evidence suggests that for some rare genetic diseases these symptoms are due to an underlying genetic pathology rather than psychological symptoms that are a result of having a chronic condition. When the rare genetic disease is undiagnosed or misdiagnosed, the management of the symptoms may be suboptimal, and as a result there is little improvement in symptom severity and quality of life. Significant delays between symptom onset and definitive diagnosis may also delay these individuals from receiving effective first-line therapies. Moreover, the prevalence of rare genetic diseases may be greatly underestimated in mental health care settings. To address the dearth of information surrounding mental health in rare genetic disease populations, a systematic review of relevant case literature was conducted to determine the diagnostic profile of rare genetic diseases with core mental health features. Here we report analyses of the time to diagnosis, misdiagnosis rate, genetic testing and treatment response before and after definitive diagnosis of the rare genetic disease.
Methods:
A systematic review of PubMed and PsychINFO was performed with a last search date of July 13, 2023. Data was and continues to be collected specifically from case reports, case series and case-control studies of 84 rare genetic diseases with well-described neuropsychiatric symptoms. Diagnostic delay, presenting symptoms, misdiagnosis rate, genetic testing results and treatment response were extracted and analyzed for each rare genetic disease.
Results:
Data abstracted from 1,221 published articles encompassing 1,838 individual cases with one of 84 rare genetic diseases revealed a mean diagnostic delay of 9.3 ± 8.7 years. There was no significant improvement in time to diagnosis over the 65-year period from 1958 to 2023. Moreover, subanlaysis further showed there was no improvement in the time to diagnosis when analyzed by the most recent 10 and 20 years. Neuropsychiatric symptoms were also reported in 68% of the included cases. Following a definitive diagnosis and optimized management of the underlying rare genetic disease, 66% of individuals experienced an improvement in at least one of their neuropsychiatric symptoms.
Conclusion:
Undiagnosed rare diseases with mental health symptoms can lead to substantial delays in optimal treatments, which may result in poor patient outcomes. Incorporating genetic testing into clinical workflows may help to decrease diagnostic delay, particularly where there are complex presentations of rare diseases that include symptoms of common mental health conditions. Providers can personalize treatment strategies to address the underlying pathology, which in turn may enhance patient outcomes and alleviate the burden of diagnostic uncertainty for those affected.
Individuals affected by rare genetic diseases can face debilitating diagnostic challenges when mental health symptoms are present. Accumulating evidence suggests that for some rare genetic diseases these symptoms are due to an underlying genetic pathology rather than psychological symptoms that are a result of having a chronic condition. When the rare genetic disease is undiagnosed or misdiagnosed, the management of the symptoms may be suboptimal, and as a result there is little improvement in symptom severity and quality of life. Significant delays between symptom onset and definitive diagnosis may also delay these individuals from receiving effective first-line therapies. Moreover, the prevalence of rare genetic diseases may be greatly underestimated in mental health care settings. To address the dearth of information surrounding mental health in rare genetic disease populations, a systematic review of relevant case literature was conducted to determine the diagnostic profile of rare genetic diseases with core mental health features. Here we report analyses of the time to diagnosis, misdiagnosis rate, genetic testing and treatment response before and after definitive diagnosis of the rare genetic disease.
Methods:
A systematic review of PubMed and PsychINFO was performed with a last search date of July 13, 2023. Data was and continues to be collected specifically from case reports, case series and case-control studies of 84 rare genetic diseases with well-described neuropsychiatric symptoms. Diagnostic delay, presenting symptoms, misdiagnosis rate, genetic testing results and treatment response were extracted and analyzed for each rare genetic disease.
Results:
Data abstracted from 1,221 published articles encompassing 1,838 individual cases with one of 84 rare genetic diseases revealed a mean diagnostic delay of 9.3 ± 8.7 years. There was no significant improvement in time to diagnosis over the 65-year period from 1958 to 2023. Moreover, subanlaysis further showed there was no improvement in the time to diagnosis when analyzed by the most recent 10 and 20 years. Neuropsychiatric symptoms were also reported in 68% of the included cases. Following a definitive diagnosis and optimized management of the underlying rare genetic disease, 66% of individuals experienced an improvement in at least one of their neuropsychiatric symptoms.
Conclusion:
Undiagnosed rare diseases with mental health symptoms can lead to substantial delays in optimal treatments, which may result in poor patient outcomes. Incorporating genetic testing into clinical workflows may help to decrease diagnostic delay, particularly where there are complex presentations of rare diseases that include symptoms of common mental health conditions. Providers can personalize treatment strategies to address the underlying pathology, which in turn may enhance patient outcomes and alleviate the burden of diagnostic uncertainty for those affected.