|LETTER TO EDITOR
|Year : 2022 | Volume
| Issue : 4 | Page : 216-218
Reflex seizures with hot water and recurrent nonconvulsive status epilepticus in a patient with triple mosaicism and ring formation of chromosome 20
Ismail Solmaz1, Filiz Azman2, Gulen Eda Utine3, Dilek Yalnizoglu4, Serap Saygi2
1 Department of Neurology; Department of Pediatric Neurology, University of Hacettepe, Ankara, Turkey
2 Department of Neurology, University of Hacettepe, Ankara, Turkey
3 Department of Pediatric Genetics, School of Medicine, University of Hacettepe, Ankara, Turkey
4 Department of Pediatric Neurology, School of Medicine, University of Hacettepe, Ankara, Turkey
|Date of Submission||29-Sep-2021|
|Date of Decision||12-Feb-2022|
|Date of Acceptance||21-Feb-2022|
|Date of Web Publication||19-Dec-2022|
Department of Neurology, Hacettepe University Faculty of Medicine, Ankara 06100
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Solmaz I, Azman F, Utine GE, Yalnizoglu D, Saygi S. Reflex seizures with hot water and recurrent nonconvulsive status epilepticus in a patient with triple mosaicism and ring formation of chromosome 20. Neurol Sci Neurophysiol 2022;39:216-8
|How to cite this URL:|
Solmaz I, Azman F, Utine GE, Yalnizoglu D, Saygi S. Reflex seizures with hot water and recurrent nonconvulsive status epilepticus in a patient with triple mosaicism and ring formation of chromosome 20. Neurol Sci Neurophysiol [serial online] 2022 [cited 2023 May 29];39:216-8. Available from: http://www.nsnjournal.org/text.asp?2022/39/4/216/364420
Ring chromosome 20 r(20) is seen in 1:30,000–60,000 births. Hypothetically, unstable subtelomeric region causes ring formation in the chromosome. Inversions, mutations, deletions, or duplications may be seen during such fusion. In r(20) formation, mosaicism can occur in lymphocytes by 1%–100%.,
Characteristic findings of r(20) syndrome are behavioral problems, cognitive dysfunction, drug-resistant epilepsy, and nonconvulsive status epilepticus (NCSE) attacks. Hot water epilepsy (HWE) is one of the reflex epilepsies reported to occur in relation to bathing habits, particularly in certain geographic regions, comprises 0.9% of all epilepsies in Turkey.,, We present a patient with NCSE attacks and nonlesional drug-resistant frontal lobe epilepsy wherein most seizures are triggered by hot water. She has triple mosaicism accompanied by r(20) which is reported for the first time with HWE.
A 20-year-old student was born following in vitro fertilization pregnancy and she had normal neurological development. Atypical absence seizures were started at 12 years of age, and she received valproic acid which failed to control seizures and was switched to ethosuximide. Subsequently, she started to experience focal seizures with or without evolution to bilateral convulsive seizures. These seizures started with vocalizations, right head deviation, bilateral hand automatism and mostly occurred during bathing with hot water. Initially, seizure duration was approximately a minute but over time, it prolonged to 20 min. Seizures persisted despite treatment with carbamazepine, vigabatrin, topiramate, gabapentin, phenytoin, primidone, oxcarbazepine, lamotrigine, and zonisamide used either alone or in various combinations. Ketogenic diet resulted in no significant benefit. Currently, she continues to have 2-3 seizures per day under polytherapy with zonisamide, clobazam, and primidone. Neurological examination was normal. Her IQ score assessed by WISC-R test was 86; neuropsychological evaluation revealed mildly impaired attention and memory.
Two habitual seizures were captured with irregular movements of the right-sided extremities, followed by inarticulate sounds and bilateral hand automatisms in video-electroencephalography (EEG) monitoring unit. Ictal EEG showed diffuse high-amplitude, slow-wave activity in the frontotemporal and frontocentral regions with occasional rhythmicity and spike waves [Figure 1]a. Intravenous diazepam was administered due to ongoing ictal activity on EEG accompanied by subtle clinical signs such as late response to questions, difficulty of counting, and naming objects for 20 min that are compatible with NCSE. Ictal activity ceased gradually following the benzodiazepine. Interictal EEG showed left frontal and bilateral frontal spikes and polyspikes [Figure 1]b. Brain magnetic resonance imaging was normal. Relative hypometabolism in the left frontal lobe was noted on positron emission tomography-computed tomography scan. Chromosome analysis revealed (46, XX, r(20)/45, XX,-20/46, XX(24)) [Figure 2]a and [Figure 2]b. Thus, the patient was diagnosed with drug-resistant focal epilepsy some triggered by hot water and intermittent NCSE attacks with mosaicism accompanied by r(20) and monosomy 20.
|Figure 1: Ictal electroencephalography showed diffuse high-amplitude, slow-wave activity in the frontotemporal and frontocentral regions with occasional rhythmicity and spike waves (a). Interictal electroencephalography showed left frontal and bilateral frontal spikes and polyspikes wave discharges during sleep (b). LFF: 1 Hz, HFF: 70 Hz. Sensitivity 200 microvolt|
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|Figure 2: The karyotype of the patient shows ring formation of chromosome r(20) (a) and monosomy (20) (b)|
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| Discussion|| |
r(20) syndrome is a adolescence-onset epileptic encephalopathy occurs usually sporadically.
A chromosomal breakage occurs at 20q13 during ring formation, resulting in deletion, and risk for epilepsy development can be explained by several potential mechanisms in r(20). First, breakage areas during ring formation are the regions where CHRNA4 and KCNNQ2 genes are programmed., These genes are KQT subgroup (KCNQ2) of nicotinic Ach receptor α-4 subunit (CHRNA4) voltage-gated K channels. Defects in these genes lead to interruption of intercellular signal transduction, resulting in autosomal dominant nocturnal frontal lobe epilepsy and benign neonatal familial seizures, respectively. These epileptic syndromes with unclear mechanisms share similar chromosomal regions with r(20) syndrome and cause interruption in signal transduction, supporting epileptic channelopathy hypothesis., Another hypothesis is delayed cell proliferation in the brain due to abnormal ring formation in chromosomes during brain development.,
The most common seizure types are drug-resistant frontal lobe seizures and intermittent NCSE attacks in r(20) syndrome, similar to our case. Our case had been on polytherapy with several ASMs as well as ketogenic diet without clear benefit.
Although some reflex epilepsies and seizures have been reported with some genetic abnormalities such as musicogenic seizures in Dravet Syndrome or eating seizures in duplication of MECP2, the genetic background of reflex seizures and epilepsies are heterogeneous and usually unknown. Recently, praxis-induced reflex epilepsy has reported in r(20) syndrome but HWE has not been reported with r(20) yet. The phenomenology of seizures in HWE is mainly concordant with temporal lobe, however, our case had frontal lobe seizures., To the best of our knowledge, this is the first case who has HWE and frontal lobe seizures with r(20) chromosome.
It was concluded that there might be a correlation between increased number of r(20) cells and phenotype but no correlation between the degree of mosaicism and refractoriness of epilepsy.,, Presumably, due to lesser r(20) chromosome, she had a good cognitive outcome despite drug-resistant seizures.
Frontal epileptic discharges and unilateral or bilateral prolonged high-voltage slow-wave pattern can be observed on EEG. In interictal EEG, 1–2 Hz delta-wave and spike-wave complexes can be observed predominantly in frontal regions with diffuse slowing of background rhythm similar to our patient's EEG findings.
Microcephaly, genital hypoplasia, dental malocclusion, micrognathia, cauliflower ear, coarse facial features, and slanting eyelids were reported in r(20) syndrome. Our patient had no dysmorphic features. Tezer et al. reported two siblings with phenotypic features and electroclinical findings of r(20) syndrome, r(20) formation were found in one sibling but not in other. Interestingly, no subtelomeric deletion could be detected in cases with r(20). Our case had a mosaic pattern involving isolated r(20) without deletion.
Monosomy 20 has been rarely reported and it is not compatible with life mostly. In rare cases of monosomy 20 survivors, phenotype varies from normal to severe motor and mental disability. Elens et al. reported a patient who had seizures accompanied by clonic facial movement, bilateral mesial temporal sclerosis, bifrontal epileptic focus on EEGs, and quartet mosaicism including r(20) and monosomy 20. In another case series, triplet mosaicism including trisomy 20 and r(20) was reported in a patient. In our case, the presence of triplet mosaicism including monosomy 20 and r(20) was considered as an extremely rare form.
In conclusion, clinicians should be aware of genetic causes in patients with drug-resistant epilepsy accompanied by NCSE attacks and reflex epilepsy such as HWE even with normal intelligence and without dysmorphic features.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
We had no additional assistance in the writing and publishing process of the article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]