| 1. |
- Frykholm, Carina, et al.
(författare)
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Stereocilin gene variants associated with episodic vertigo : expansion of the DFNB16 phenotype
- 2018
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 26:12, s. 1871-1874
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Tidskriftsartikel (refereegranskat)abstract
- Vestibular disorders comprise a heterogeneous group of diseases with transient or permanent loss of vestibular function. Vestibulopathy is in most cases associated with migraine, Meniere disease, hereditary ataxias, or sensorineural hearing loss. We identified two brothers and their first cousin affected by hearing loss and episodic vertigo. The brothers were homozygous STRC nonsense variant [c.4027 C> T, p.(Q1343*)], whereas their first cousin was compound heterozygous for the STRC nonsense variant and a 97 kb deletion spanning the entire STRC gene. Clinical investigations confirmed pathological vestibular responses in addition to a characteristic DFNB16 hearing loss. The STRC gene encodes Stereocilin in the cochlea and in the vestibular organ where it ensheathes the kinocilium of the otolithic membranes. Stereocilin is associated with the gel overlaying the vestibular kinocilia, suggesting a role for the protein in sensing balance and spatial orientation. Our findings support such a function for Stereocilin in the vestibular organ and expand the phenotype associated with DFNB16.
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| 2. |
- Tomanovic, Tatjana
(författare)
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Persistent geotropic nystagmus : a different kind of cupula pathology
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In patients with positional vertigo a persistent positional direction-changing nystagmus (PDCN) of apogeotropic direction (a-PDCN) in the supine yaw plane has been described earlier 1-5. It has been suggested that the cupula in the lateral semicircular canal has a higher specific weight than the surrounding endolymph making the cupula sensitive to gravity. This condition is known as ”heavy cupula”. We have described, in Paper I, a geotropic persistent direction-changing nystagmus (g-PCDN) in patients during vestibular crisis6. In addition, when the patient is in the supine position and the head is turned slowly from one side to the other it is possible to discern a zero zone where the geotropic nystagmus is absent. This is accomplished when the head is turned circa 10-20 degrees laterally. Theoretically this occurs when the longitudinal axis of the affected cupula is aligned with the gravitational vertical 7-9. On the assumption that a position dependent nystagmus such as persistent a-PDCN is caused by a heavy cupula in one of the lateral semicircular canals (LSCC), thus it could be hypothesized that a g-PDCN can be caused by the cupula that is lighter than the surrounding endolymph. We have called this new diagnostic entity “light cupula”. A similar phenomenon of a PDCN is seen in subjects with positional alcohol nystagmus (PAN) 10-18. This phenomenon is based on the” buoyancy hypothesis” 19,20. In order to reproduce a clinical condition where the density of the cupula was lower or higher than the surrounding endolymph we examined the nystagmus pattern in different head positions in unilaterally deafferented patients during the stage of PAN 1 and PAN 2 respectively21,22. We compared results of nystagmus direction during PAN 1 (Paper II) with the findings in patients with light cupula in the LSCC (Paper I). Nystagmus direction in both supine and prone lateral head positions was compatible with that of a light cupula. However, the nystagmus directions at head straightforward in prone and supine position as well as the localization of zero zones deviated from the pattern seen in patients with a light cupula21. We followed up nystagmus characteristics and nystagmus pattern in Paper III on the labyrinthectomized subjects during the stage of PAN 222. This study showed persistent a-PDCN according the theory 12. The nystagmus pattern in pitch plane was of opposite to that during PAN 1. Nystagmus in supine position was directed to the affected side during PAN 2 and to non-affected side during PAN 1 but the zero zones in both studies is found on the affected side. We were interested to see if the results concerning the nystagmus pattern in the experimental studies could be applied to patients during vestibular disability with g-PDCN permitting a lateralization of the affected side. In Paper IV we examined an extended series of 20 patients with g-PDCN nystagmus pattern during acute vestibular disability and at follow up 1-7 years later. Nystagmus patterns in different head positions were recorded, both caloric and otolith tests were carried out. Concomitant auditory symptoms as an indication of the affected side were rare. The slow phase velocity (SPV) of geotropic nystagmus was low and of equal intensity and did not present an indication of the affected side according to Ewald's second law23. With nystagmus analysis we found evidence for a cupula that is sensitive to gravitation, but did not find an applicable pattern for simply determination of the affected side by analysing nystagmus direction in the pitch plane and in lateral head positions. There was a high prevalence of migraine (40%) and the patients also had problems with recurrent vertigo (80%). The vestibular tests were pathologic in 60% of the patients.
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