Mosaicism and phenotype in ring chromosome 20 syndrome

Abstract

Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder characterized by epilepsy, mild to moderate mental impairment, and malformation. Patients generally show mosaicism in 1-100% of lymphocytes with r(20). We report here a patient with r(20) syndrome who exhibited mild phenotype with the small ratio of mosaicism (13%) with r(20). Although previous small-scale studies concluded that the mosaicism ratio was unrelated to clinical phenotype, our reassessment of all 57 reported cases has revealed that the ratio is significantly associated with age at seizure onset, intelligence quotient, and malformation, but not with the response of epilepsy to drug treatment. Our results provide important clinical information and prediction for r(20) syndrome.

Mosaic ring 20 with no detectable deletion by FISH analysis: Characteristic seizure disorder and literature review

“…The phenotype of this case shared many clinical features of previously reported ring chromosome 20 cases [Nishiwaki et al, 2005], especially the form of epilepsy (Table I).…”

“…These observations suggested that specific genes on chromosome 20 are responsible for the typical seizure phenotypes in ring chromosome 20. Nine cases with supernumerary mosaic ring chromosome 20 with two normal 20's and one or two additional ring 20's have been reported [Nishiwaki et al, 2005]. Seven cases had one additional ring chromosome 20, and two cases carried one to two additional rings.…”

“…To determine whether it is also a common disorder in other ring chromosomes, we reviewed epilepsy frequencies in a total of 403 cases with ring chromosomes including 22 autosomes and X chromosome (Fig. 3) [Palka et al, 1986;Fagan et al, 1988;MacDermot et al, 1990;Matalon et al, 1990;Freyberger et al, 1991;Calabrese et al, 1994;Migliori et al, 1994;Lurie, 1995;Flejter et al, 1996;Lanzi et al, 1996;Wahlstrom et al, 1996;Conte et al, 1997;Cutenese et al, 2000;Rodriguez et al, 2000;Tonk et al, 2000;Barajas-Barajas et al, 2001;Dee et al, 2001;Stankiewicz et al, 2001;He et al, 2002;Muroya et al, 2002;Urban et al, 2002;van Karnebeek et al, 2002;Concolino et al, 2003;Ishmael et al, 2003;Morimoto et al, 2003;Parmar et al, 2003;Shashi et al, 2003;Battini et al, 2004;Bedoyan et al, 2004;Le Caignec et al, 2004;Leppig et al, 2004;Rope et al, 2004;Tumer et al, 2004;Zhang et al, 2004;Alkuraya et al, 2005;Nishiwaki et al, 2005]. Only ring chromosomes 14, 17, and 20 are strongly associated with seizure disorders.…”

“…Development may be normal until onset of seizures. However, ring chromosome 20 is characterized by a seizure disorder with non-convulsive status epilepticus, mostly expressed as complex partial seizures with prolonged duration [Inoue et al, 1997;Canevini et al, 1998;Kobayashi et al, 1998;Nishiwaki et al, 2005]. It has typical electroencephalography (EEG) signatures including normal or diffuse slowing of background activity, long beats of rhythmic synchronous high-voltage slow waves with or without spike component predominantly in the frontal or frontotemporal area, and non-convulsive status epilepticus [Kobayashi et al, 1998].…”

A girl with neurofibromatosis type 1, atypical autism and mosaic ring chromosome 17

“…Second, due to problems with chromatid separation, ring chromosomes are mitotically unstable, and give rise to a spectrum of secondary chromosomal defects including monosomy, double rings, and marker chromosomes [Vogel and Motulsky, 1997]. Various cell lines coexist within the patient in a mosaic state, and the phenotype can depend on the composition and frequency of mosaicism, and its distribution in different tissues [Nishiwaki et al, 2005]. Because of the instability of the ring chromosomes it was proposed that carriers, irrespective of the chromosome involved, suffer from a universal ''ring syndrome'' [Kosztolanyi, 1987].…”