A Novel Type of Autosomal Dominant Episodic Nystagmus Segregating with a Variant in the FRMD5 Gene

Figures & data

Figure 1. Flowchart showing enrolment of participants.

Table 1. Characteristics of the 12 affected participants. Data obtained from questionnaires and medical records.

	Affected participants (n = 12)
Gender (male/female)	5/7
Median age (years) (range)	51.5 (13–81)
Median age at onset (years) (range)	2.5 (0.5–8)
Other diagnoses/conditions
Epilepsy (n)	0
Migraine (n)	4
Other neurological disease (n)	0
Psychiatric disease (n)	1
Myotonia congenita (n)	5
Strabismus (n)	0
Previous neuroradiology examination with normal results (n)	7
Previous electroencephalogram with normal results (n)	1
Previous clinical neurological examination with normal results (n)	4

Figure 2. (a) Pedigree of the family with a Ser375Phe (c.1124C>T) variant in the FRMD5 gene. Plus and minus indicate individuals with and without the variant, respectively. Squares: male; circles: female; slash: deceased. Filled symbols indicates affected family members and unfilled healthy family members. (b) Chromatogram of a heterozygous carrier of a C to T change at nucleotide 1124 of FRMD5 (NM_032892). (c) Chromatogram showing a wild-type sequence in nucleotide 1124 of FRMD5 (NM_032892). (d) Alignment of a partial sequence of human FRMD5 protein with 12 protein sequences.

Figure 3. Number of episodes of nystagmus during the last 12 months, reported by each of the affected participants. Some subjects gave a range for the number of episodes, in which case, the mean value was used.

Table 2. Characteristics of nystagmus episodes in the 12 affected participants, obtained from questionnaires. (Some data are missing for three participants since they did not respond to all questions. When subjects answered a question with a range of numbers, the mean of the range was used.).

Median age at onset (range) (years)	2.5 (0.5–8)
Median number of episodes in the past year (range)	6.75 (0–20)
Median maximal number of episodes per day (range)	1 (0–3)
Median minimal number of episodes per day (range)	0 (0–1)
Median age when frequency of episodes decreased^1 (range)(years)	50 (32.5–53)
Median age when frequency of episodes reached a maximum (range)(years)	20.25 (1–50)

¹The four youngest subjects (aged 13–26) reported that the number had not yet decreased, and these data were excluded.

Table 3. Percentage of the total number of affected subjects (n = 12) reporting associated symptoms during ongoing episodes of nystagmus, precipitating factors that could trigger an episode, and alleviating factors that reduced the severity and number of nystagmus episodes.

	%
Associated symptoms
Diplopia	92
Nausea	83
Oscillopsia	83
Poor balance	75
Vertigo	75
Impaired vision	75
Fixed gaze	50
Vomiting	17
Precipitating factors
Bright light	92
Strenuous activity	83
Emotional stress	75
Tiredness	67
Hunger	50
Crowded places	50
Strong wind	50
Sweating	42
Strong colours	33
Specific patterns	25
Caffeine	0
Alleviating factors
Rest	100
Closing the eyes	83
Looking downwards	75
Avoiding stress	58
Eating regularly	50
Shielding from the sun with a cap or sunglasses	42
Gaze fixation	17

Figure 4. Analysis of video recordings from an affected family member, showing an upbeat nystagmus with variable amplitude and frequency.