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In late nineteenth-century London, fourteen-year-old Enola Holmes, much younger sister of detective Sherlock Holmes, turns to Florence Nightingale for help when her investigation into the disappearance of a Crimean War widow grows cold.

Jules Montgomery, navigating London with a recent hearing loss, joins forces with detectives Watson and Holmes to uncover the truth behind a missing classmate, and finds that her unique powers of observation may hold the key to solving both the case and the mystery of the detectives' presence in the 21st century.