The genes identified in these two syndromes are the nicotinic acetylcholine receptor alpha-4 subunit and potassium voltage-gated channel subfamily KQT member 2 respectively. Mutations in these genes lead to the clinical manifestations found in these disorders. It is theorized that deletions in these regions from the ringed chromosome may lead to epilepsy in affected patient. A similar association between a ring chromosome and an autosomal-dominant disease has been reported for ring 17 chromosome and Miller-Dieker syndrome. The recurrence risk for ring chromosome 20 syndrome is very low. The ring formation is typically not identified in parents, and occurs de novo during pre-natal development. Diagnosis
The ring 20 abnormality may be limited to as few as 5% of cells, so a screen for chromosomal mosaicism is critical. Newer array technology will not detect the ring chromosome and the standard metaphase chromosome analysis has been recommended. A karyotype analysis examining at least 50 cells should be requested to properly detect mosaicism. Treatment
Successful management of seizures plays a key role in improving quality of life. Antiepileptic medications are the main therapies for seizures; however, it appears that seizures in this syndrome do not respond well to drugs. In the cases reported in literature, numerous new and old antiepileptic drugs have been tried, but no one drug appears to be more efficacious than others. Therefore, no recommendations can be made regarding the selection of the most appropriate antiepileptic drug.
Many of these patients experience their seizures only during sleep. They can have seemingly bizarre features as they originate from the frontal lobe of the brain. Often, individuals with ring chromosome 20 syndrome are initially found to have complex partial seizures of frontal lobe origin, though imaging studies do not show a corresponding structural brain abnormality. In certain patients, these seizures may secondarily generalized. Individuals from the ages of 0–17 years should be considered for ring 20 chromosome analysis if they have: predominantly complex partial seizures, medically refractory cryptogenic epilepsy, Lennox-Gastaut-like features with no cause identified, frequent subtle nocturnal seizures, an EEG showing prolonged high voltage frontally dominant slowing intermixed with spikes or sharp waves, an EEG showing overlapping features of continuous slow spike and wave discharges in sleep (CSWS) and electrical status epilepticus in sleep (ESES), and/or subsequent cognitive impairment/learning difficulties/mild retardation.These patients will typically have a normal childhood development until onset of epilepsy and lack evidence of dysmorphism or other congenital malformations. Genetics
Rather than the typical linear pattern of a chromosome, deletion of the endings of a chromosome can lead to ring formation. A chromosome has two arms, one long and one short. Deletion of the short arm of chromosome 20 does not appear to result in epilepsy; however, terminal deletion of the long arm is associated with epilepsy. Therefore, some gene loss from the terminal segment could be responsible for the manifestation of epilepsy in ring chromosome 20 syndrome. The most common breakpoint in patients is in the q13.33 region of chromosome 20.