Alternative titles; symbols
SNOMEDCT: 90128006; ORPHA: 166409; DO: 0060281;
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38): 6:40,500,001-46,200,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6p21.1 | Photoparoxysmal response 1 | 132100 | Autosomal dominant | 2 |
The photoparoxysmal response (PPR), also referred to as photosensitivity, is defined as the abnormal occurrence of cortical spikes or spike and wave discharges on electroencephalogram (EEG) in response to intermittent light stimulation (Doose and Waltz, 1993).
Photosensitivity is a frequent finding in patients with idiopathic generalized epilepsy (see 600669), especially those with juvenile myoclonic epilepsy, suggesting a common epileptogenic pathway for both phenomena. The comorbidity of the 2 disorders suggests that presence of PPR may also increase the risk for epilepsy (Stephani et al., 2004; Tauer et al., 2005).
Genetic Heterogeneity of Photoparoxysmal Response
The PPR1 locus has been mapped to chromosome 6p21. See also PPR2 (609572), mapped to chromosome 13q31, and PPR3 (609573), mapped to chromosome 7q32.
Bickford et al. (1952) observed and described the 'photoconvulsive response' as a disturbance of cortical function. The photoconvulsive response was characterized by a diffuse, synchronous spike-wave discharge pattern on EEG that was unrelated to the frequency of the light stimulus, continued after the light stimulus ceased, and was associated with general seizure activity. The authors suggested a link to myoclonic epilepsy.
In a study of first-degree relatives of patients with photoconvulsive reactions, Rabending and Klepel (1970) concluded that the response was an age-dependent variation of a genetically determined trait.
Doose and Gerken (1972) evaluated a total of 645 sibs of 208 probands with photosensitivity and 133 probands without photosensitivity. A photoparoxysmal response was observed in 22.9% of sibs of PPR-positive probands, compared to 11.4% of PPR-negative probands and 7.6% of controls. The PPR showed an age-dependent effect, occurring mainly during childhood. A bimodal distribution in childhood (peaks at 6-8 years and 11-14 years) was seen particularly in female sibs of PPR-positive probands. Moreover, the response was more common in girls than boys. Doose and Gerken (1972) concluded that there was a genetic component to the PPR.
Waltz et al. (1992) characterized different EEG patterns of the photoparoxysmal response in 135 photosensitive probands with at least 1 photosensitive first-degree relative. Sixty-five probands had generalized idiopathic epilepsy and 70 had no history of epilepsy. Four PPR patterns were observed in order of increasing severity: type 1, spikes restricted to the occipital region; type 2, parietooccipital spikes with a biphasic slow wave; type 3, parietooccipital spikes with a biphasic slow wave and spread to the frontal region; and type 4, generalized spikes and waves. A PPR was found in 39% of sibs of probands with seizures and 44% of sibs of probands without seizures, suggesting that the 2 features were genetically independent. The incidence of PPR in sibs of probands with type 4 discharges (38%) was the same as that in sibs of probands with types 1-3 discharges (35%), suggesting that the genetic impact of less expressive forms of photosensitivity is the same as in generalized spikes and waves. In addition, type 4 discharges occurred more often in probands with epilepsy and their sibs compared to probands without epilepsy and their sibs, suggesting that genetic predisposition for generalized epilepsy is associated with a more severe phenotypic expression of PPR. Strikingly, the maximum incidence of PPR occurred in individuals between 6 and 15 years of age, and PPR patterns types 3 and 4 occurred more often in younger than older relatives, indicating age-dependent expression. Waltz et al. (1992) concluded that generalized spikes and waves are one of several variable phenotypic expressions of photosensitivity, and suggested that the different discharge types of PPR may represent different levels of expression of the same genetically determined trait.
In a review article, Doose and Waltz (1993) noted that consideration of the strict definition of a photoconvulsive response suggested by Bickford et al. (1952), associated uniquely with generalized spike and wave discharges, would result in a high association of the phenomenon with epilepsy.
Waltz and Stephani (2000) found that 50% of sibs with 1 PPR-positive parent showed the PPR between ages 5 and 15 years compared to 15% of sibs from families in which neither parent had PPR. Sibs in the first group also had a higher seizure rate (19%) than sibs in the second group (4%). Waltz and Stephani (2000) concluded that a PPR in parents is a major determinant of the risk for PPR in offspring. The results were consistent with autosomal dominant inheritance with age-dependent penetrance of the trait. In addition, the findings suggested that the PPR trait may influence the risk for epilepsy.
Friedlander (1959) discussed a hereditary pattern of 'cerebral light sensitivity.' The data collected by Davidson and Watson (1956) on 12 families were consistent with dominant inheritance with reduced penetrance. There was no instance of male-to-male transmission.
De Haan et al. (2005) reported monozygotic 16-year-old twin boys who were concordant for the PPR trait but discordant for trait manifestation. The affected twin developed a generalized tonic-clonic seizure while being exposed to intense, long-lasting visual stimulation by a recreational stroboscope lamp. In the months before the seizure, he had exposure to the same stroboscope lamp at several different weekly parties. After the seizure, the boy became hypersensitive to visual stimuli. His unaffected twin brother did not attend the same parties and had never been exposed to the stroboscope lamp. Photosensitivity EEG testing, performed with flash frequencies ranging between 2 and 60 Hz, showed that both twins had occipital and generalized PPR activity and their father had occipital PPR activity. The mother had a normal EEG and no PPR. De Haan et al. (2005) concluded that the clinical PPR symptom discordance observed in this family was linked to repeated environmental exposure to stroboscopic light flashes in the affected twin. The light may have visually 'primed' the affected twin, serving to move a genetic predisposition to a fully expressed phenotype. The findings were similar to some stimulus-induced epilepsies seen in animals.
By linkage analysis of 19 unrelated families in which at least 2 sibs had PPR, Tauer et al. (2005) identified a putative disease locus on chromosome 6p21.1 (MOD score of 4.30 at marker D6S2427 under a recessive mode of inheritance). A locus for juvenile myoclonic epilepsy (EJM3; 608816) had been mapped to the same region.
Bickford, R. G., Sem-Jacobsen, C. W., White, P. T., Daly, D. Some observations on the mechanism of photic and photo-metrazol activation. Electroenceph. Clin. Neurophysiol. 4: 275-282, 1952. [PubMed: 12989085] [Full Text: https://doi.org/10.1016/0013-4694(52)90052-7]
Davidson, S., Watson, C. W. Hereditary light sensitive epilepsy. Neurology 6: 231-261, 1956.
de Haan, G.-J., Trenite, D. K.-N., Stroink, H., Parra, J., Voskuyl, R., van Kempen, M., Lindhout, D., Bertram, E. Monozygous twin brothers discordant for photosensitive epilepsy: first report of possible visual priming in humans. Epilepsia 46: 1545-1549, 2005. [PubMed: 16146452] [Full Text: https://doi.org/10.1111/j.1528-1167.2005.44104.x]
Doose, H., Gerken, H. On the genetics of EEG-anomalies in childhood. IV. Photoconvulsive reaction. Neuropadiatrie 4: 162-171, 1972.
Doose, H., Waltz, S. Photosensitivity--genetics and clinical significance. Neuropediatrics 24: 249-255, 1993. [PubMed: 8309513] [Full Text: https://doi.org/10.1055/s-2008-1071552]
Friedlander, W. J. Epilepsy. Am. J. Psychol. 1: 623-628, 1959.
Gerken, H., Doose, H., Volzke, E., Volz, C., Hien-Volpel, K. F. Genetics of childhood epilepsy with photic sensitivity. (Letter) Lancet 291: 1377-1378, 1968. Note: Originally Volume I.
Rabending, G., Klepel, H. Fotokonvulsivreaktion und fotomyoklonus: altersabhangige genetisch determinierte varianten der gesteigerten fotosensibilitat. Neuropadiatrie 2: 164-172, 1970. [PubMed: 5001029] [Full Text: https://doi.org/10.1055/s-0028-1091851]
Stephani, U., Tauer, U., Koeleman, B., Pinto, D., Neubauer, B. A., Lindhout, D. Genetics of photosensitivity (photoparoxysmal response): a review. Epilepsia 45 (suppl. 1): 19-23, 2004. [PubMed: 14706040] [Full Text: https://doi.org/10.1111/j.0013-9580.2004.451008.x]
Tauer, U., Lorenz, S., Lenzen, K. P., Heils, A., Muhle, H., Gresch, M., Neubauer, B. A., Waltz, S., Rudolf, G., Mattheisen, M., Strauch, K., Nurnburg, P., Schmitz, B., Stephani, U., Sander, T. Genetic dissection of photosensitivity and its relation to idiopathic generalized epilepsy. Ann. Neurol. 57: 866-873, 2005. [PubMed: 15929039] [Full Text: https://doi.org/10.1002/ana.20500]
Waltz, S., Christen, H.-J., Doose, H. The different patterns of the photoparoxysmal response--a genetic study. Electroenceph. Clin. Neurophysiol. 83: 138-145, 1992. [PubMed: 1378379] [Full Text: https://doi.org/10.1016/0013-4694(92)90027-f]
Waltz, S., Stephani, U. Inheritance of photosensitivity. Neuropediatrics 31: 82-85, 2000. [PubMed: 10832582] [Full Text: https://doi.org/10.1055/s-2000-7478]