Keywords
Ring 20 chromosome - r(20) syndrome - Intractable epilepsy
1
Case
A 10 year old boy, first by birth order, born of non-consanguineous marriage was referred
for evaluation of refractory epilepsy. He had history of refractory seizures since
2 years of age. Perinatal history was insignificant. There was no family history of
epilepsy or mental retardation. Child did not have obvious dysmorphic features. Seizures
were hypo motor with staring and psychomotor arrest associated with drooling and unresponsiveness
without much motor involvement, lasting for few minutes followed by postictal drowsiness
and sleep. No drops or myoclonic jerks or tonic seizures were seen. Initially seizures
used to occur only in awake state however with advancing age he started getting seizures
in sleep state as well. Seizure frequency also increased from once in a month to 1
to 2 per week. Sometimes he used to get episodes of altered behavior or confusion
with intermittent blinking of eyes and decreased responsiveness, lasting for few hours
(atypical absence or non-convulsive status epilepticus – NCSE). His motor milestones
were normal but, he showed significant delay in cognition and speech. His Developmental
quotient at 10 years of age was 60% only.
Magnetic resonance imaging (MRI) of brain with 3 T resolution at 7 year of age did
not reveal any obvious dysplasia or other abnormality. Electroencephalography (EEG)
at 4 year of age ([Fig. 1]) showed bi-frontal spike-wave discharges. EEG gradually showed worsening over the
years with generalized but predominantly bi frontal discharges with slow waves and
spikes ([Figs. 2] and [3]). Metabolic work up including simultaneous blood and CSF sugar, tandom mass spectroscopy
(TMS) for amino acids and carnitine profile and urine gas chromatography and mass
spectroscopy (GCMS) for organic acids were normal.
Fig. 1– EEG with bipolar longitudinal montage at 4 year of age with occasional Frontal
discharges.
Fig. 2– EEG with bipolar longitudinal montage at 6 year of age – bi-frontal synchronous
discharges.
Fig. 3– EEG with bipolar longitudinal montage at 8 year of age – bi-frontal maximum
generalized discharges.
His karyotype analysis of 100 metaphases showed ring shaped chromosome 20 ([Fig. 4]). Diagnosis of ring chromosome 20 or r(20) syndrome was made. Ring chromosome 20
syndrome is a rare cause of refractory epilepsy.
Fig. 4– Karyotyping showing ring chromosome 20 – red arrow. (For interpretation of
the references to color in this figure legend, the reader is referred to the web version
of this article.)
He was treated with multiple antiepileptics including valproate and clobazam. Topiramate
and oxcarbamazepine in view of recurrent seizures. Despite of giving antiepileptic
drugs in optimum dose for optimum period, his seizure frequency was not controlled.
Hence he was labeled to have refractory epilepsy and started on classical ketogenic
diet since last 6 months with only marginal response.
2
Discussion
Ring chromosome 20 syndrome was 1st described in 1972 by Atkins et al. and by various
other groups separately.[1] Exact prevalence of ring chromosome 20 is not known. Overall genetic and chromosomal
abnormalities constitute 2–3% of all epilepsy cases. Epilepsy is often the first sign
of ring 20 syndrome. Children with ring chromosome 20 syndrome do not show any dysmorphic
features and usually have normal psychomotor development at onset of seizures.[1]
[2]
Seizures start at around 2–5 year of age and typically do have brief partial seizures
initially and later may have generalized seizures with episodes of non-convulsive
status epilepticus (NCSE) with prolonged confused states and clouding of consciousness.
In present case, patient had seizure onset at 2 years of age, initially brief seizures
and then progressed to refractory epilepsy, sometimes associated with status and NCSE.
Nocturnal frontal lobe seizures have been described.[3] Gradually, there is cognitive decline as described in our case. No obvious dysmorphic
features have been described.[1]
[2]
[3]
Few authors have described possibility of relationship between percentage of mosaicism
and clinical features, however, it has been also postulated that in addition some
other factors must be the trigger of this peculiar type of epilepsy.[3]
[4] It is a sporadic condition with no risk of recurrence.[3]
EEG described in ring 20 chromosome condition is generalized 2–3 Hz high amplitude
rhythmic slow delta with superimposed spike or sharp waves of bi-frontal maximum.[2]
[3]
[4]
[5] Index case also showed bi-frontal synchronous discharges at the presentation and
later generalized but bi-frontal predominant discharges. Characteristically, these
are less spiky as compared to slow spike wave discharges of Lannox Gestaut syndrome
(LGS).[2]
[3]
[4]
[5] Also tonic seizures and drops characteristic of LGS were not seen in our case. MRI
imaging of brain is usually normal, although few cases with cortical dysplasia or
focal atrophy has been described.[5] Neuroimaging findings were unremarkable in our case.
It is postulated that, loss of telomeric material at both ends of chromosome 20, causes
refractory epilepsy. The genes postulated for the epilepsy like KCNQ2 and CHRNA4 –
both located on telomeric regions.[6] Biraben et al. studied F-dopa-PET in ring chromosome 20 syndrome and found that
there is reduced uptake of dopa in putamen and caudate and postulated that it causes
impaired seizure interruption and refractory epilepsy.[7]
Ring 20 syndrome is refractory to antiepileptic medications. Only one case of seizure
control by antiepileptic medications has been reported.[8] There are no specific antiepileptic drugs recommended but occasional good results
have been obtained with a combination of valproate and lamotrigine.[2]
[3]
[5] There is no role of resective surgery.[3]
[8] There is a case report of focal cortical resection done in a case ring 20 syndrome
with no seizure control.[3] Vagal nerve stimulation for the refractory epilepsy with ring 20 syndrome has showed
partial response.[9]
To summarize, it is important to evaluate patients with refractory epilepsy to rule
out genetic causes like ring 20 syndrome. Genetic cause should be suspected in patients
with refractory epilepsy and normal MRI brain. Ring 20 chromosome is a rare genetic
cause for refractory epilepsy.
Authors’ contribution
Dr. Umesh Kalane – data collection, literature search and writing the case, Dr. Chaitanya
Datar – literature search and writing the manuscript, Dr. Shilpa Kalane – final editing
and writing the manuscript.
Conflicts of interest
The authors have none to declare.
Ethical
Informed consents were taken from parents of patients prior to this work.
