Characterizing Common Phenotypes Across the Childhood Dementia Disorders: A Cross-sectional Study From Two Australian Centers.

BACKGROUND: Childhood dementias are a group of rare pediatric conditions characterized by progressive neurocognitive decline. Quantifying and characterising phenotypes to identify similarities between specific conditions is critical to inform opportunities to optimize care and advance research. METHODS: This cross-sectional study recruited primary caregivers of children (<18 years) living with a dementia syndrome from neurology and metabolic clinics in Sydney and Adelaide, Australia. Sociodemographic and clinical data were collated. Behavior, eating, sleep, pain, and neurological disability were assessed using validated tools, including Strengths and Difficulties, Child Eating Behaviour, and Children's Sleep Habits questionnaires and visual analog of pain and modified Rankin scales. Data were analyzed with descriptive statistics. RESULTS: Among 45 children with 23 different dementia syndromes, the modified Rankin Scale demonstrated at least moderate neurological disability and functional dependence in 82% (37/45). Families reported delays in receiving an accurate diagnosis following initial symptoms (mean: 1.6 ± 1.4 years, range: 0-5 years). The most prevalent phenotypes included communication, comprehension, or recall difficulties (87%, 39/45); disturbances in sleep (80%, 36/45); appetite changes (74%, 29/39); mobility issues (53%, 24/45); and hyperactive behavior (53%, 21/40). Behavioral problems had a "high" or "very high" impact on everyday family life in 73% (24/33). CONCLUSIONS: Childhood dementia disorders share substantial behavioral, motor, sensory, and socioemotional symptoms, resulting in high care needs, despite their vast heterogeneity in age of onset and progression. Considering their unifying characteristics under one collective term is an opportunity to improve treatment, provide quality care, and accelerate research.

Childhood Dementia: A Collective Clinical Approach to Advance Therapeutic Development and Care.

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.