More severe epilepsy and cognitive impairment in the offspring of a mother with mosaicism for the ring 20 chromosome
Introduction
Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder characterized by refractory epilepsy, cognitive impairment, behavioural problems and sometimes dysmorphic features (Atkins et al., 1972, Schinzel, 2001). About 60 cases have been reported. Patients generally show mosaicism, the ratio of r(20) varying from 1–100% in lymphocytes. Typical features of epilepsy in r(20) syndrome are drug-resistant epileptic seizures and periods of nonconvulsive status epilepticus (NCSE) (Inoue et al., 1997, Augustijn et al., 2001, Biraben et al., 2004). Cognitive problems are common and vary from mild learning disabilities to moderate mental retardation (Back et al., 1989, Augustijn et al., 2001, Biraben et al., 2004, Nishiwaki et al., 2005, Macleod et al., 2005). Earlier it was concluded that the mosaicism ratio was unrelated to the clinical phenotype. However, a reassessment of 57 published cases showed that the ratio significantly correlated with the age of onset of the seizures, the intelligence quotient and malformations, but not with the response to antiepileptic drug (AED) treatment (Nishiwaki et al., 2005).
Reported cases with r(20) syndrome tend to be sporadic. Only two families, one with two affected members and the other with two members and one carrier, have previously been described (Back et al., 1989, Canevini et al., 1998). In this report we enlighten the clinical features in a family in which three members are affected in successive generations.
Section snippets
Methods
We report the clinical characteristics of three patients with r(20) syndrome in the same family, the mother and her two children. All three patients have been followed up by Kuopio Epilepsy Center since the time they were first referred because of their seizures and epilepsy was diagnosed. Multiple EEG, ambulatory EEG and video EEG are available for all three patients. Three or more successive neuropsychological assessments with age-specific tests during the follow-up period have been performed
Clinical data
The clinical characteristics of the patients are presented in Table 1. The mother was first examined due to epilepsy after the first generalized convulsive seizure in 1989 at the age of 26 years. However, her medical history revealed that she had had staring spells without aura, abrupt stopping of activities and difficulties in understanding speech for two years, especially when tired. During the first 3 years after the diagnosis, seizure control was unsatisfactory with diurnal seizures and
Discussion
The main feature of r(20) syndrome is epilepsy, which was diagnosed in the mother at the age of 26, in the daughter at the age of 7 and in the son at the age of 5. The onset of epilepsy was rather late for the mother compared to the mean age of 6 years in a reassessment of the published cases in the literature (Nishiwaki et al., 2005). However, the earliest age for the onset of epilepsy in r(20) syndrome has been neonatal (Burnell et al., 1985, Thomsen et al., 1989, Lancman et al., 1993, Chawla
Conclusion
All familial cases reported show higher levels of mosaicism in succeeding generations associated with a more severe phenotype. This discovery concerns the severity of epilepsy and of cognitive dysfunction. The mechanism of progression between generations remains unknown.
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Cited by (24)
A further case of familial ring chromosome 20 mosaicism - molecular characterization of the ring and review of the literature
2019, European Journal of Medical GeneticsSpecificity of electroclinical features in the diagnosis of ring chromosome 20
2018, Epilepsy and BehaviorCitation Excerpt :Febrile seizures were absent in the six patients with R20 from our series, in contrast with some studies [5,15,26], but consistent with what has been published in the majority of previous descriptions. Abnormal behavior in our series was milder than usually reported in the literature [1,3,6,10,12,14,15,17,28,31,32], and consisted mainly in apathy and lack of initiative in two patients. This behavior correlates with frontal lobe involvement, probably secondary to abundant epileptiform activity, and has been linked to dopaminergic deficit by previous authors [24].
Epilepsy in ring chromosome 20 syndrome
2016, Epilepsy ResearchRing chromosome 20
2012, European Journal of Medical GeneticsCitation Excerpt :Additional case reports of individuals presenting with epilepsy led to the description of a ring chromosome 20 syndrome [23,24]. Since then, nearly 100 patients in 70 reports on have been described, most with intractable epilepsy, variable cognitive impairment and/or behavioral problems [1,8,9,12,16,17,25–31]. In some of these cases, development was normal until seizure onset, suggesting that the syndrome be considered an epileptic encephalopathy.
Ring chromosome 20 syndrome: Electroclinical description of six patients and review of the literature
2012, Epilepsy and BehaviorCitation Excerpt :Response to therapy and severity of phenotype were previously assumed to be independent of the number of mosaic cells [6,13,15]. Still, a case report of a familial case of ring chromosome 20 is in conflict with the latter supposition [23]. The unresponsiveness of the epilepsy to antiepileptic drugs (AED) in patient 4 also could be ascribed to the multifactorial origin of the seizures as explained earlier.
The evolving electroclinical syndrome of "epilepsy with ring chromosome 20"
2012, SeizureCitation Excerpt :Dysfunction of striatal dopamine in patients with r(20) has been described, which may contribute to apathy and mutism in few.16 Familial occurrences with variability of the phenotypes have been described rarely.7,8 The level of mosaicism was found to be contributory to the increasing severity of manifestations in successive generations.8