What is r(20) syndrome?

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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. Two distinct forms are recognized, mosaic and non-mosaic ring chromosome 20 epilepsy syndrome. 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.(1,2,3 )


Epilepsy is a constant feature of this syndrome and in many cases is intractable and drug resistant. Seizure frequency depends on percentage of mosaicism with almost 100% occurrence in the non-mosaic form. Seizures are complex partial in type and reported as episodes of sudden fear altered awareness with staring, oral automatisms, unspecified automatic behavior, focal motor symptoms and/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. 45, 6, 78 Nocturnal seizures are a frequent occurrence in this syndrome. Seizures can often be long in duration with waxing and waning intensity. Secondary generalized tonic clonic seizures are rarely seen.

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 frontal 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 (9, 10). Prolonged runs of interictal bifrontal sharp and slow wave complexes are observed in prolonged sleep recordings and may represent a pathognomonic EEG pattern (11).

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. .12


Major and minor malformations including facial dysmorphism are subtle or absent in the mosaic form. Patients with non-mosaic ring 20 often have dysmorphic features and short stature. In contrast patients with the more common mosaic form appear physically normal. This lack of dysmorphic features in mosaic ring 20 syndrome and omission of chromosomal testing in patients leads to delayed diagnosis (13). Rare cases of mosaic 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). 1415

Ring chromosome 20 epilepsy syndrome is often diagnosed as idiopathic/ cryptogenic (no etiology identified) partial frontal lobe epilepsy disorder. Can also be 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). 1617


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. Patients with the non-mosaic r(20) are often diagnosed earlier because of the presence of dysmorphic features and developmental delay leading to early chromosomal testing. 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. Newer genetic testing such as chromosomal microarray (CMA) will not detect this syndrome as structural aberration cannot be detected by this method. Neuroimaging studies and metabolic studies are unrevealing in this disorder. 18 ,19 202122. Video-EEG monitoring is valuable in diagnosis and identification of characteristic EEG patterns. Invasive EEG monitoring with intracranial electrodes is not indicated as no discrete epileptic focus is expected to be detected in a chromosomal syndrome.


Management of children with r(20) is symptomatic. Seizure control is very important. Seizures are typically difficult to treat. Overall treatment is more challenging in patients with non-mosaic form. In mosaic forms response to treatment may inversely correlate with percentage of mosaicism. Antiepileptic drugs (AEDs) 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. In addition treatment response does not differ between older and newer AEDs. Unfortunately seizures are difficult to control with antiepileptic medication and may require consideration of alternative treatments.

Other alternates to antiepileptic drug treatment are ketogenic diet (KD) and vagus nerve stimulation (VNS). Epilepsy surgery is not an option. 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) syndrome20 2324,25

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.


Ring Chromosome 20 is a refractory partial epilepsy syndrome with frontal lobe features. Two distinct forms are recognized the more common mosaic and the rare non-mosaic form. Patients with mosaic form do not have dysmorphism leading to delayed chromosomal testing and delayed diagnosis. In contrast non-mosiac form have developmental delay and dysmorphisms leading to early chromosomal testing and earlier diagnosis. Definitive diagnosis can only be established by conventional chromosomal karyotyping with mosaic screening. No deletion of genetic material is seen in the mosaic forms. Deletions have been reported in patients with the non-mosaic patients. Treatment is often difficult with continued medically refractory seizure with overall better prognosis in the mosaic type.


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