Elsevier

Epilepsy Research

Volume 73, Issue 1, January 2007, Pages 122-128
Epilepsy Research

More severe epilepsy and cognitive impairment in the offspring of a mother with mosaicism for the ring 20 chromosome

https://doi.org/10.1016/j.eplepsyres.2006.09.006Get rights and content

Summary

Purpose

Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder. Cases tend to be sporadic. We elucidate the characteristics of an inherited r(20) mosaicism by describing the clinical features of three family members: a mother and her two children.

Results

The mosaicism rate of the mother was 10% and that of the children 40%. The mother experienced her first epileptic seizures at 24 years of age. Epilepsy was diagnosed two years later. After an unstable period lasting 3 years, she has been seizure-free for 13 years on a combination of valproate and lamotrigine. She has normal intelligence with full working capacity. The daughter exhibited her first epileptic seizures at the age of 7 years and she continues to have seizures weekly. The first epileptic seizures in the son were observed at 5 years of age. The son's epilepsy has been drug resistant from the onset, and a vagal nerve stimulator (VNS) has been ineffective. Psychomotor development was normal in both children up to the onset of epilepsy. Learning difficulties increased throughout school age and both children needed special educational programs. Neuropsychological evaluations have shown deterioration of cognitive levels. Both children had behavioural problems during school age but no longer in adolescence. All three subjects are nondysmophic, normocephalic and of normal growth.

Conclusion

In this family the phenotype of r(20) mosaicism seems to be more severe in the successive generation along with a greater level of mosaicism. The aggravated clinical picture in inherited r(20) mosaicism concerned the onset of epilepsy, drug responsiveness, the cognitive level and behavioural features.

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.

References (17)

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