Adie (1926) first delineated narcolepsy as a separate and specific entity. It is a sleep disorder characterized by attacks of disabling daytime drowsiness and low alertness. The normal physiologic components of rapid eye movement (REM) sleep, dreaming and loss of muscle tone, are separated and also occur while the subject is awake, resulting in half-sleep dreams and episodes of skeletal muscle paralysis and atonia (cataplexy and sleep paralysis). Unlike normal sleep, that of narcolepsy often begins with REM activity and the time taken to fall asleep is shorter than normal. In contrast to animal models, human narcolepsy is not a simple genetic disorder. Most human cases of narcolepsy are sporadic and carry a specific HLA haplotype (Peyron et al., 2000). Familial cases are the exception rather than the rule, and monozygotic twins show only partial concordance (25 to 31%) (Mignot, 1998). Genetic Heterogeneity of Narcolepsy Additional narcolepsy loci have been mapped to chromosomes 4 (NRCLP2; 605841), 21q (NRCLP3; 609039), 22q13 (NRCLP4; 612417), 14q11 (NRCLP5; 612851), and 19p13.2 (NRCLP6; 614223). NRCLP7 (614250) is caused by mutation in the MOG gene (159465) on chromosome 6p22. Resistance to narcolepsy is associated with minor alleles of a SNP and a marker in the NLC1A gene (610259) on chromosome 21q22.

Narcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.\n\nNarcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. "Sleep attacks" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.\n\nAnother common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.\n\nNarcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.\n\nSome people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive slowly progressive neurologic disorder characterized by imbalance due to cerebellar gait and limb ataxia with cerebellar atrophy on brain imaging, nystagmus, dysarthria, and peripheral sensory neuropathy with decreased or absent deep tendon reflexes. More variable features include vestibular dysfunction, chronic cough, autonomic dysfunction, saccadic pursuit, and pyramidal signs (extensor plantar responses). Most patients have onset in late adulthood, although earlier onset has been reported. Rare patients have features suggestive of lower motor neuron involvement (Szmulewicz et al., 2011, Miyatake et al., 2022).

ADCADN is an autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy/cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression (summary by Winkelmann et al., 2012).