Although clinical features associated with the T666MCACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease.
The common manifestations of the disease in patients with PLP1 mutations or duplications in this study were nystagmus in early infancy, dysmyelination revealed by magnetic resonance imaging (MRI), and auditory brain response abnormalities.
Pelizaeus-Merzbacher disease (PMD; MIM#312080) is a rare X-linked leukodystrophy presenting with motor developmental delay associated with spasticity and nystagmus.
A patient who developed nystagmus at 16 months and progressive spastic ataxia at 18 months was found to have a 19-base pair (bp) deletion of a G-rich region near the 5' end of intron 3 of the PLP gene.
Based on eight novel patients and all CASK-mutation positive males reported previously three phenotypic groups can be distinguished that represent a clinical continuum: (i) MICPCH with severe epileptic encephalopathy caused by hemizygous loss-of-function mutations, (ii) MICPCH associated with inactivating alterations in the mosaic state or a partly penetrant mutation, and (iii) syndromic/nonsyndromic mild to severe ID with or without nystagmus caused by CASK missense and splice mutations that leave the CASK protein intact but likely alter its function or reduce the amount of normal protein.
To scrutinize the etiology of a four-generation Japanese family with autosomal dominant nystagmus associated with anterior and posterior segment anomalies, the PAX6 gene was examined.
Patients with C-terminal CASK mutations also present with nystagmus and, strikingly, we show that these mutations specifically disrupt interaction with FRMD7.
There were characteristic clinical features such as hypotonia and optic atrophy for SCA1; hyporeflexia for SCA2; nystagmus, bulging eye, and dystonia for SCA3; and macular degeneration for SCA7.
Areflexia, slow saccades and hypopallesthesia predominated in SCA2; nystagmus, pyramidal signs or areflexia restricted to the legs in SCA 3; and retinal degeneration, pyramidal signs and slow saccades in SCA 7.
SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades.
Clinically, CORDX3 shares some features with CSNB2 but is distinguishable from CSNB2 in that it is progressive, can begin in adulthood, has no nystagmus or hyperopic refraction, has only low grade astigmatism, and in dark adaptation lacks cone threshold and has small or no elevation of rod threshold.