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What is r(20) Syndrome?

An Overview of r(20) Epilepsy Syndrome

Ring chromosome 20 epilepsy syndrome, also known as r(20) syndrome, is a rare chromosomal anomaly resulting from a break on each arm of chromosome 20 resulting in ring formation. In r(20) syndrome, the breakpoint of most patients is in the p13q13.33 region of chromosome 20. This syndrome is characterized by medically intractable epilepsy, nocturnal subtle seizures, behavioral problems and mild mental impairment. Unlike other chromosomal aberrations, dysmorphism (major or minor congenital malformation) is rarely reported.

This syndrome is undoubtedly an under-diagnosed condition. Dr. Borgaonkar and his colleagues at Johns Hopkins University first reported on 3 patients with ring chromosome 20 syndrome in 1976. Since then, only 60 cases of r(20) have been reported in literature. To date there is still no published data on the incidence and prevalence of this syndrome. This disorder appears to be pan-ethnic and non-gender specific. Cases of this syndrome have been reported from many different parts of the world involving different ethnicities. Almost all cases which have been reported are sporadic with no family history. However, with more widespread cytogenetic chromosomal karyotyping in non-etiological cases of epilepsy, more cases of r(20) will undoubtedly be recognized.1


Epilepsy is a constant feature of this syndrome and in many cases is intractable and drug resistant. Seizures are often complex partial in type and reported as episodes of altered consciousness with staring, oral automatisms, unspecified automatic behavior, focal motor symptomsand/or head turning. Subtle nocturnal behavioral changes such as stretching, rubbing and turning have been observed which resemble normal arousal behavior. In addition, subtle nocturnal seizures (SNS) and subtle nocturnal frontal lobe seizures (SNFLS) are also reported Seizures are often difficult to control with antiepileptic medications. 2, 3, 4, 5, 6

Electroencephalography (EEG)

The Electroencephalographic (EEG) features of the cases of r(20) syndrome described in medical literature may show frequent bursts of sharply contoured theta waves and prolonged runs of high voltage frontally dominant slowing, intermixed with spikes or sharp waves. EEG patterns in r(20) syndrome have been delineated as non-convulsive status epilepticus. These characteristic patterns may be combined with large portions of normal appearing EEG activity. 7, 8

Cognition & Behavior

Cognition is usually normal before the onset of epilepsy, but there is the possibility of mental impairment if seizures are frequent and persistent. Individuals may have normal cognition despite periods of poorly controlled epilepsy and others may have profound learning disabilities and require help with all aspects of daily life. Behavioral problems can vary from minor concentration and attention difficulties with high levels of activity to profound problems. Several of the children reported in medical literature have been described to have periods of very difficult behavior often associated with poor seizure control. The behavior and cognitive difficulties do vary with time and may worsen with increasing seizures. However, the child may regain these lost skills with improved seizure control.9


Abnormal physical features are often lacking. Major and minor malformations including facial dysmorphism are subtle or absent. This lack of dysmorphic features and often omission of chromosomal testing in patients with refractory epilepsy leads to delayed diagnosis. Rare cases of r(20) syndrome with dysmorphic features published in literature consisted of microcephaly (head circumference is smaller than normal because brain has not developed properly or has stopped growing), plagiocephaly (deformed skull), dental malocclusions (misalignment of teeth and/or incorrect relation between the teeth of the two dental arches), micrognathia (is an abnormal smallness of the lower jaw), cauliflower-shaped ears, and coarse facial features with slanting eyelids (obliquely downward and outward). 10, 11

r(20) is often confused with other epilepsy syndromes, most notably Lennox-Gastaut syndrome (LGS) which is characterized by medically refractory mixed intractable seizures. Unlike LGS, seizures in r(20) epilepsy syndrome cause frequent, violent, brief seizures at night, usually beginning in childhood. Unlike r(20) syndrome the seizures in autosomal dominant nocturnal frontal lobe epilepsy (ADNFE) can be easily controlled with antiepileptic drugs. The nocturnal EEG pattern in r(20) may also have overlapping features of continuous spike and wave discharges during slow wave sleep (CSWS) and electrical status epilepticus in sleep (ESES). 12, 13

Fig.1 Mechanisms 
Two DNA breaks in each arm at the top and bottom causing:
• Distortion of Chromosomal morphology
• Proximal end fusion and ring formation
• Loss of distal material as ends break away
• Potential loss of Genetic material and
• Dysregulation of gene expression
• Alteration in cellular life cycle
• Formation of Ring 20 associated with epilepsy
Ring formation in other chromosomes may cause mental retardation

Fig.2 Mechanisms
• Fusion of dysfunctional Telomere of the same chromosome
• Shortening of telomeric DNA and Recombination with the other arm of the same chromosome
• Detachment of protective proteins from chromosomal ends
• May or may not be associated with Loss of Genetic material
• Possible alteration of gene expression


Diagnosis of ring chromosome 20 syndrome can be made by recognition of certain characteristic clinical features; however, definitive diagnosis requires chromosomal testing of the affected person's cells. This is most easily done by looking at the chromosome pattern (karyotype) in blood cells but any other tissue including skin could be examined. Since chromosomal analysis or karyotype testing is not a routine investigation when epilepsy first presents, the diagnosis of r(20) syndrome may be delayed or go unrecognized. In other words, some people with difficult to control epilepsy may have a ring chromosome 20 but be unaware of it. Almost all parents of individuals with r(20) syndrome have no evidence of r(20) syndrome in their own blood chromosome analysis. A few individuals, typically relatives of affected patients , have been found to have a ring chromosome 20 without any evidence of symptoms. Why these people are protected against development of epilepsy remains unknown. Neuroimaging studies and metabolic studies are unrevealing in this disorder. 14, 15, 16, 17, 18


Management of children with r(20) is symptomatic. Seizure control is very important. Seizures are typically difficult to treat. Antiepileptic drugs are the mainstay and first line of treatment as is for other intractable epilepsy syndromes. From the study of published literature, no one drug seems to be better than any other drug and patients are frequently exposed to multiple antiepileptic drugs. Unfortunately seizures are difficult to control with antiepileptic medication and may require consideration of alternative treatments.

Other alternates to antiepileptic drug treatment are epilepsy surgery, ketogenic diet (KD) and vagus nerve stimulation (VNS). Epilepsy in r(20) syndrome is not amenable to resective surgery because of a lack of discrete epileptic areas. Vagus nerve stimulation has been successful in a few cases reported in the literature. KD is a high fat, low carbohydrate diet used for other intractable childhood epilepsies. There are no published reports on use of ketogenic diet in patients with r(20) syndrome, however its efficacy and safety is well established in other intractable epilepsies like Lennox-Gastaut syndrome. The role of other unconventional treatments of epilepsy is not established for the treatment of r(20) syndrome. 19, 20, 21

The long term outcome of the syndrome is not known. It is not lethal, however a patient who has frequent epileptic seizures is at risk of other complications of epilepsy including status epilepticus and sudden unexpected death in epilepsy (SUDEP). The best predictor is likely to be the degree of seizure control.


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3.      Inoue Y, Fujiwara T, Matsuda K, Kubota H, Tanaka M, Yagi K, Yamamori K, Takahashi Y.Ring chromosome 20 and nonconvulsive status epilepticus. A new epileptic syndrome. Brain. 1997 Jun;120 ( Pt 6):939-53. 

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7.      Kobayashi K, Ingaki M, Sasaki M, Sugai K, Ohta S, Hashimoto T. Characterstic EEG findings in ring 20 syndrome as a diagnosis. Electroencephalography Clin Neurophysiol 1998 Oct:107 258-262. 

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9.      Herrgard E, Mononen T, Mervaala E, Kuusela L, Aikia M, Stenback U, Paakkonen L, Airaksinen RL, Kalviainen R. More severe epilepsy and cognitive impairment in the offspring of a mother with mosaicism for the ring 20 chromosome. Epilepsy Res. 2007 Jan;73(1):122-8. 

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14.    Kosztolanyi, G. Does "ring syndrome" exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet. 1987 Feb;75(2):174-9. 12. 

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