Chapter 1 10 Figure 1: Clinical presentation of 4H syndrome. Neurological (blue) and non-neurological (white) clinical presentations. Created using BioRender.com. 4H SYNDROME – Current Treatments Due to its multisystem involvement, 4H leukodystrophy requires multidisciplinary care involving several subspecialists, including endocrinologists, neurologists, dentists, and clinical geneticists. Current treatment strategies are symptom-based, focusing on managing the broad range of clinical features associated with the disorder. Management of the three hallmark symptoms involves supportive care such as physical and occupational therapy for motor and neurological issues that might be caused by hypomyelination, hormone replacement therapy (HRT) for hypogonadotropic hypogonadism (Billington et al., 2015; Nwatamole et al., 2024), and specialized dental evaluations to address hypodontia. While these interventions can improve the quality of life for affected individuals, there is currently no curative therapy for 4H syndrome. Its progressive nature and clinical variability stress the urgent need for novel therapeutic strategies targeting and curing the underlying pathology. Identifying specific therapeutic targets at the molecular and cellular level will be crucial in developing future disease-modifying therapies. Advances in understanding 4H syndrome’s genetic and cellular basis hold promise for translating research findings into meaningful clinical interventions. In summary, 4H syndrome is a relatively prevalent leukodystrophy with a highly variable clinical presentation and progressive disease course. Current treatments remain supportive, focusing on symptom management and improving patients’ quality of life, but they lack curative potential (Adang et al., 2017). To provide novel perspectives new curative treatment strategies are urgently needed. To develop these, we need to understand the targets for therapies.
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