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Desmond se mudou com a família de Savannah, Georgia para o Bronx aos 3 anos. Frequentou escola católica até que se graduou na Fordham Preparatory School, uma escola de ensino médio Jesuíta, tendo causado alguns problemas por ser hiperativo. Depois do ensino médio, ele frequentou o Manhattan College, mas foi expulso após somente 6 semanas. Depois disso, trabalhou em várias outras profissões antes de atuar. Através da atuação, Desmond encontrou uma válvula de escape para sua veia hiperativa.
Seu primeiro papel foi o de Aulon na cine-biografia de Joana d'Arc de Luc Besson. Logo ele passou a ocupar importantes papéis em obras como O Buraco, Navio Fantasma e Pânico na Floresta. Atualmente interpreta o detetive Joseph Quinn na série Dexter.
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