Childhood dementias are a group of over 100 rare and ultra-rare pediatric conditions that are clinically characterized by chronic global neurocognitive decline. This decline is associated with a ...progressive loss of skills and shortened life expectancy. With an estimated incidence of one in 2800 births and less than 5% of the conditions having disease-modifying therapies, the impact is profound for patients and their families. Traditional research, care, and advocacy efforts have focused on individual disorders, or groups classified by molecular pathogenesis, and this has established robust foundations for further progress and collaboration. This review describes the shared and disease-specific clinical changes contributing to childhood dementia and considers these as potential indicators of underlying pathophysiologic processes. Like adult neurodegenerative syndromes, the heterogeneous phenotypes extend beyond cognitive decline and may involve changes in eating, motor function, pain, sleep, and behavior, mediated by physiological changes in neural networks. Importantly, these physiological phenotypes are associated with significant carer stress, anxiety, and challenges in care. These phenotypes are also pertinent for the development of therapeutics and optimization of best practice management. A collective approach to childhood dementia is anticipated to identify relevant biomarkers of prognosis or therapeutic efficacy, streamline the path from preclinical studies to clinical trials, increase opportunities for the development of multiple therapeutics, and refine clinical care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Childhood dementia is a devastating and under-recognized group of disorders with a high level of unmet need. Typically monogenic in origin, this collective of individual neurodegenerative ...conditions are defined by a progressive impairment of neurocognitive function, presenting in childhood and adolescence. This scoping review aims to clarify definitions and conceptual boundaries of childhood dementia and quantify the collective disease burden.
A literature review identified conditions that met the case definition. An expert clinical working group reviewed and ratified inclusion. Epidemiological data were extracted from published literature and collective burden modelled.
One hundred and seventy genetic childhood dementia disorders were identified. Of these, 25 were analysed separately as treatable conditions. Collectively, currently untreatable childhood dementia was estimated to have an incidence of 34.5 per 100 000 (1 in 2900 births), median life expectancy of 9 years and prevalence of 5.3 per 100 000 persons. The estimated number of premature deaths per year is similar to childhood cancer (0–14 years) and approximately 70% of those deaths will be prior to adulthood. An additional 49.8 per 100 000 births are attributable to treatable conditions that would cause childhood dementia if not diagnosed early and stringently treated. A relational database of the childhood dementia disorders has been created and will be continually updated as new disorders are identified (https://knowledgebase.childhooddementia.org/).
We present the first comprehensive overview of monogenic childhood dementia conditions and their collective epidemiology. Unifying these conditions, with consistent language and definitions, reinforces motivation to advance therapeutic development and health service supports for this significantly disadvantaged group of children and their families.
Dementia is usually considered a disease of the elderly but there are many genetic diseases that cause dementia in childhood. Elvidge et al. refine the definition of childhood dementia and determine that the collective incidence of currently untreatable childhood dementias equates to 34.5 per 100 000 (1 in 2900 births).
Childhood dementias are a group of rare and ultra-rare paediatric conditions clinically characterised by enduring global decline in central nervous system function, associated with a progressive loss ...of developmentally acquired skills, quality of life and shortened life expectancy. Traditional research, service development and advocacy efforts have been fragmented due to a focus on individual disorders, or groups classified by specific mechanisms or molecular pathogenesis. There are significant knowledge and clinician skill gaps regarding the shared psychosocial impacts of childhood dementia conditions. This systematic review integrates the existing international evidence of the collective psychosocial experiences of parents of children living with dementia. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched four databases to identify original, peer-reviewed research reporting on the psychosocial impacts of childhood dementia, from the parent perspective. We synthesised the data into three thematic categories: parents' healthcare experiences, psychosocial impacts, and information and support needs. Nineteen articles met review criteria, representing 1856 parents. Parents highlighted extensive difficulties connecting with an engaged clinical team and navigating their child's rare, life-limiting, and progressive condition. Psychosocial challenges were manifold and encompassed physical, economic, social, emotional and psychological implications. Access to coordinated healthcare and community-based psychosocial supports was associated with improved parent coping, psychological resilience and reduced psychological isolation. Analysis identified a critical need to prioritize access to integrated family-centred psychosocial supports throughout distinct stages of their child's condition trajectory. This review will encourage and guide the development of evidence-based and integrated psychosocial resources to optimise quality of life outcomes for of children with dementia and their families.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Sanfilippo syndrome is a group of rare, complex, and progressive neurodegenerative lysosomal storage disorders that is characterized by childhood dementia. The clinical management of patients with ...progressive neurological decline and multisystem involvement requires a multidisciplinary team with experience in the management of neurodegenerative disorders. Best practice guidelines for the clinical management of patients with these types of rare disorders are critical to ensure prompt diagnosis and initiation of appropriate care. However, there are no published standard global clinical care guidelines for patients with Sanfilippo syndrome. To address this, a literature review was conducted to evaluate the current evidence base and to identify evidence gaps. The findings were reviewed by an international steering committee composed of clinical experts with extensive experience in managing patients with Sanfilippo syndrome. The goal was to create a consensus set of basic clinical guidelines that will be accessible to and informed by clinicians globally, as well as providing a practical resource for families to share with their local care team who may not have experience with this rare disease. This review distills 178 guideline statements into an easily digestible document that provides evidence-based, expert-led recommendations for how to approach common management challenges and appropriate monitoring schedules in the care of patients with Sanfilippo syndrome.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Childhood dementia is a devastating and under‐recognised group of conditions with a high level of unmet need. Typically monogenic in origin, this collective of neurodegenerative ...conditions are defined by a progressive impairment of neurocognitive function, presenting in infancy, childhood or adolescence.
Method
We undertook a scoping review and burden of illness study to understand the spectrum of childhood dementia conditions and their impact. A literature review identified conditions that met the case definition and an expert clinical working group reviewed and ratified inclusion. Epidemiological data were extracted from published literature and collective incidence, prevalence and life expectancy were modelled.
Result
Over 140 individual genetic conditions were identified that can be consistently defined as childhood dementia with the largest proportion of births belonging to the lysosomal disease and mitochondrial disease categories. Collectively the incidence is surprisingly high at 1 in 2,900 births and the life expectancy is low, with most affected children not surviving into adulthood. A relational database of the childhood dementia disorders has been created and will be continually updated as new disorders are identified (https://knowledgebase.childhooddementia.org/).
Conclusion
This scoping review highlights the importance of grouping these conditions as a phenotypic syndrome, rather than individually rare diseases, in keeping with the approach to adult dementia. Opportunities exist to address overlapping disease mechanisms and utilise therapeutic platforms for multiple childhood dementia conditions to tap into significant economies of scale. Collaboration with adult dementia researchers on common disease attributes is also expected to be mutually beneficial.
By unifying these conditions, we have highlighted the many unmet needs of this significantly disadvantaged group of children and young people and the data presented here will enable advocacy for systemic change in treatment, care, and support for them and their families.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
7.
A new initiative to tackle childhood dementia Elvidge, Kristina L.; Smith, Nicholas J.; Hemsley, Kim M. ...
Molecular genetics and metabolism,
February 2021, 2021-02-00, Volume:
132, Issue:
2
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
8.
Early signs of Duchenne muscular dystrophy Kristina Elvidge; Klair Bayley
Australian journal of child and family health nursing,
12/2016, Volume:
13, Issue:
2
Journal Article
Duchenne muscular dystrophy is the most common muscular dystrophy in children, affecting 1 in 3500 newborn boys. Children are typically diagnosed around the age of five but parents often raise ...concerns several years earlier. Patient organisations around the world are working to raise awareness of the early signs of Duchenne to improve rates of early diagnosis so that children can gain early access to gold standard levels of care, clinical trials and emerging therapies. Importantly, it also gives parents and other family members access to genetic counselling to help them plan future pregnancies. Early signs that all health professionals can look out for include delayed motor development, waddling gait, trouble with stairs and getting up off the floor, falling often, enlarged calves, speech and language delay and behavioural/learning dificulties. At the first suspicion of Duchenne, a simple blood test for creatine kinase (CK) can be done, and if levels are raised, referral for genetic testing made.
