An autosomal dominant syndrome of hemiplegic migraine, nystagmus, and tremor

Abstract

A mother and son suffer from hemiplegic migraine with onset in childhood. Both have nystagmus which has not changed for many years, but the date of onset is uncertain. They have an asymmetrical tremor, clinically indistinguishable from essential tremor. Neuroophthalmological examination revealed inability to produce smooth pursuit, gaze-paretic nystagmus, rebound nystagmus, failure of fixation suppression of the vestibuloocular reflex both horizontally and vertically, and low gain of the optokinetic system. These abnormalities, confirmed by electrooculography, are commonly seen in disease of the cerebellum and brainstem. Treatment with propranolol and pizotyline lessened the number of episodes of hemiplegia and improved the tremor. Hemiplegic migraine has been reported in association with nystagmus, retinal degeneration, deafness, and ataxia in varying combinations in three other families with autosomal dominant inheritance. These associated neurological manifestations likely represent system degenerations rather than the effect of repeated ischemia imputable to the migraine itself. The syndrome of hemiplegic migraine, tremor, and ocular smooth pursuit system disorder seen in this family appears to be inherited as a single autosomal dominant trait, although more than one autosomal dominant gene may be involved.

Migraine comorbidity: from genotype to phenotype

“…A study of 20 families with benign essential tremor reported that 26% of affected members also co-segregated for migraine with aura [23]. Interestingly, essential tremor has been reported in some FHM1-linked families who also have cerebellar dysfunction and in another FHM family with nystagmus and ocular motility changes suggestive of brainstem-cerebellar dysfunction.…”

Familial Hemiplegic Migraine with Prolonged Coma and Cerebellar Atrophy: CACNA1A T666M Mutation in a Korean Family

“…Most cases showed vasodilation or hyperperfusion during aura, which can differentiate this condition from ischemia (15-18). However, vasoconstriction was reported in a few cases (19, 20). Neither the severity of symptoms nor the time point of evaluation explained this discordance.…”

Abnormal Eye Movements in Children

“…96 In children, rebound nystagmus may accompany gaze-evoked nystagmus in many inherited conditions, including paroxysmal hereditary ataxias, 97 giant axonal neuropathy, 98 and familial hemiplegic migraine. 99 Bruns Nystagmus Occasionally, a tumor of the cerebellopontine angle becomes large enough to cause a small-amplitude, high-frequency nystagmus on contralateral gaze, and large amplitude, low-frequency nystagmus on ipsilateral gaze. The former results from disruption of ipsilateral afferent vestibular input (secondary to compromise of the eight cranial nerve), which causes the eyes to drift back toward primary position from contralateral gaze; this defect results in generation of corrective saccades away from the side of the lesion.…”