What is ring chromosome 20 syndrome?

Ring Chromosome syndrome (RC20) is one of a number of chromosomal disorders associated with refractory epilepsy. A ring chromosome is formed by the fusion of two arms of a chromosome during pre-natal development.1 Why the formation of the ring causes epilepsy and other symptoms of the syndrome is not well understood.

The age of the onset of the syndrome has been reported between one day of postnatal life to 17 years.2 Development is usually normal before the onset of seizures. Clinically this syndrome is characterized by frequent nocturnal subtle seizures and EEG showing prolonged high voltage frontally dominant slowing intermixed with spikes or sharp waves.3,4 This syndrome is also characterized by behavioral problems, mild mental retardation, cognitive impairment and learning disabilities.

Epilepsy appears to be the first and major clinical symptom of this syndrome, is a constant feature, and is often drug resistant.5 Seizures associated with RC20 syndrome are often complex partial and reported as episodes of altered consciousness with staring, oral automatisms, unspecified automatic behavior, focal motor symptoms and/or head turning.6 Subtle nocturnal behavioral changes such as stretching, rubbing, turning-resemble arousal, subtle nocturnal seizures (SNS), and subtle nocturnal frontal lobe seizures (SNFL) have also been reported in studies of RC20 syndrome patients.5

How is this syndrome diagnosed?

Ring Chromosome 20 syndrome is diagnosed by recognition of the features outlined above and through looking at the pattern of chromosomes in 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.7 Epilepsy is not present in all individuals with RC20 syndrome; however, it is the most consistent clinical feature. Unlike other chromosomal disorders with epilepsy, dysmorphism and other congenital malformations are rarely a part of this condition.8,9

Children can be misdiagnosed with Lennox-Gastaut syndrome or Landau-Kleffner syndrome. These two epilepsy syndromes have clinical similarities to RC20 syndrome and are characterized by frequent seizures, decline in learning ability and behavior and are often termed as cognitive epileptic encephalopathies. RC20 syndrome phenotype can also be mistaken for autosomal dominant nocturnal frontal lobe epilepsy (ADNFE). ADNFE is a familial partial epilepsy causing frequent, violent, brief seizures at night.10 Seizures usually begin in childhood and are easily controlled with carbamazepine unlike seizures in RC20 syndrome. The EEG features in RC20 syndrome may also have overlapping features of continuous slow spike and wave discharges in slow wave sleep (CSWS) and electrical status epilepticus in sleep (ESES).

How common is ring chromosome 20 syndrome?

RC20 syndrome is undoubtedly a rare condition. To date there are no published data on the incidence or prevalence of this syndrome. More than 50 cases have been reported in the medical literature. Since chromosomal analysis or karyotype testing is not a routine investigation when refractory epilepsy first presents, the diagnosis of RC20 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.

Management and Treatment

Since seizures with RC20 syndrome are typically difficult to treat, seizure control is very important. Every case is different and complex. Antiepileptic drugs are the mainstay and first line of treatment, however no one drug has been shown to be better than others. Patients are frequently exposed to multiple antiepileptic drugs. Epilepsy in RC20 syndrome is not amenable to resective surgery because of the lack of a focal epileptogenic region. Vagus nerve stimulation has been successful in a few cases reported in the literature.11


References

  1. 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.
  2. Serrano-Castro PJ, Aguilar-Castillo MJ, Olivares-Romero J, Jimenez-Machado R, Molina-Aparicio MJ. Ring chromosome 20: an epileptic channel disorder. Rev Neurol. 2001 Feb 1-15;32(3):237-41. Review. Spanish.
  3. Augustijn PB, Parra J, Wouters CH, Joosten P, Lindhout D, van Emde Boas W. Ring chromosome 20 epilepsy syndrome in children: electroclinical features. Neurology. 2001 Sep 25;57(6):1108-11.
  4. Kobayashi K, Inagaki M, Sasaki M, Sugai K, Hashimoto T, Ohta S. EEG findings opf ring chromosome 20 and their diagnostic significance [abstract]. No to Hattatsu 1996; Suppl: 171.
  5. 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: 939-53. Review.
  6. Canevini MP, Sgro V, Zufari O, Canger R, Carrozzo R, Rossi E, Ledbetter D, Mincucci F, Vignoli A, Piazzini A, Guidolin L, Saltarelli A, Bernardina BD. Chromosome 20 ring: a chromosomal disorder associated with a particular electroclinical pattern. Epilepsia. 1998 Sep; 39(9): 942-51.
  7. Garcia-Cruz D, Vasquez AI, Perez-Rulfo D, Davalos NO, Penaloza J, Garcia-Ortiz JE, Patino-Garcia B, Sanchez-Corona J. Ring-20-syndrome and loss of telomeric regions. Annales de Genetique 2000; 43: 113-6.
  8. Borgaonkar DS, Lacassie YE, Stoll C. Usefulness of chromosome catalog in delineating new syndromes. Birth Defects 1976; 12(5):87-95.
  9. Macleod S, Mallik A, Tolmie JL, Stephenson JB, O' Regan ME, Zuberi SM. Electro-Clinical phenotypes of chromosome disorders associated with epilepsy in the absence of dysmorphism. Brain & Development 2005; 27: 118-124.
  10. Scheffer IE, Bhatia KP, Lopes-Cendes I, Fish DR, Marsden CD, Andermann E. Autosomal dominant nocturnal frontal lobe epilepsy: a distinctive clinical disorder Brain 1995; 118: 61-73.
  11. Chawla J, Sucholeiki R, Jones C, Silver K. Intractable epilepsy with ring chromosome 20 syndrome treated with vagal nerve stimulation: case report and review of the literature. J Child Neurol. 2002 Oct;17(10):778-80.

About the Ring Chromosome 20 Foundation

After years of testing, misdiagnosis, and a difficult journey to find medical treatment, the Ford family was told that the reason their young daughter Cara was having frequent and severe seizures was because of ring chromosome 20 syndrome. With so much uncertainty and little information about the syndrome available, Cara's father, Stewart Ford decided to establish a Foundation to fund research and projects so that families and doctors can better understand this condition and its treatment.

The purpose of the Ring Chromosome 20 Foundation is to promote awareness of the syndrome and the importance of chromosomal testing in children with refractory epilepsy. The Foundation is based in New York City and in London. For more information about this syndrome and the Foundation, please visit www.ring20.org.

Authored by: Gregory L. Holmes | MD on 1/2004
Reviewed by: Steven C. Schachter | MD on 11/2006
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