This chapter reviews the type and prevalence of sleep problems including daytime sleepiness in a range of commonly presenting genetic syndromes and diseases. It covers the chromosomal abnormalities and genetic programming malformations of the nervous system. The chapter discusses the inherited metabolic disorders and heredodegenerative diseases. It describes the neurodevelopmental syndromes with genetic compound, and reviews the genetically based neuromuscular diseases. Excessive daytime sleepiness (EDS) is the most common sleep-related symptom in the Prader-Willi syndrome. Smith-Magenis syndrome is a severe neurodevelopmental disorder characterized by mental retardation with distinctive behavioral characteristics, dysmorphic features and an abnormal circadian pattern of melatonin ascribed to an intersticial deletion of chromosome 17. Neuromuscular diseases include a wide spectrum of motor unit diseases starting with the affection of motor neuron in the brainstem and spinal cord, continuing through myasthenic syndromes, muscle dystrophies and congenital myopathies, myotonic syndromes and ending with hereditary motor and sensory polyneuropathies (HMSN).