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PubMed · 7696677

Down syndrome: a multidisciplinary perspective.

Abstract

Trisomy 21, a genetic disorder resulting from a chromosomal abnormality, is one of the most common forms of mental disability in the United States. Individuals with Down syndrome frequently present with a constellation of medical problems including conductive hearing loss and, to a lesser degree, sensorineural hearing loss. As part of a health care team, audiologists must be sensitive to and aware of medical conditions prior to establishing intervention strategies. Medical conditions, by necessity, precede audiologic interventions and, therefore, a close working relationship among team members is critical. Yet, audiologic and communication interventions should be established at the earliest possible time for maximizing an individual's development potential. This article stresses the importance of a multidisciplinary team in the provision of services so that prevention of further disabilities, improved outcomes of medical interventions, and appropriate habilitative and educational planning may ensue.

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A O Diefendorf, M J Bull, D Casey-Harvey, R T Miyamoto, M L Pope, J J Renshaw, R L Schreiner, M Wagner-Escobar. 1995. Down syndrome: a multidisciplinary perspective.. https://pubmed.ncbi.nlm.nih.gov/7696677/

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Fasudil induces anti-inflammatory transcriptomic changes and increased proliferation in human trisomy 21 neural progenitor cells.

Down syndrome (DS) results from trisomy for human chromosome 21 and is the most frequent genetic cause of intellectual disability. No effective treatments currently exist that improve neurodevelopment and cognition. Atypical brain development in individuals with DS is apparent before birth, which suggests that the optimal time to begin administration of therapies is prenatally. Human neural progenitor cell (NPC) cultures provide a tractable in vitro model system to examine the effects of trisomy 21 (T21) on neurodevelopment and to measure the effects of pharmacological interventions. Here, we report the results of preclinical studies evaluating 24 candidate therapies. RNA sequencing analyses found that euploid and T21 NPCs showed different transcriptomic responses to five candidate pharmacotherapies. The Rho-associated coiled-coil kinase inhibitor fasudil increased proliferation of T21 NPCs, reduced expression of inflammatory pathway genes in T21 NPCs, and reduced markers of inflammation in LPS-stimulated microglial model systems. These results demonstrate that fasudil can alter multiple T21-associated abnormalities in a beneficial manner, suggesting that fasudil warrants further study as a candidate prenatal pharmacotherapy for DS.

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