Familial ring (20) chromosomal mosaicism

Abstract

Ring (20) chromosomal mosaicism defined by two cell lines (one normal and the other with the ring) has been demonstrated in lymphocyte and fibroblast cultures from three members of a family through two generations. Two carriers of the ring chromosome were affected and showed the typical signs of r(20) syndrome including mental retardation, microcephaly, behavioral disorders, and epilepsy. The epilepsy is characterized by complex partial seizures sometimes evolving secondarily into generalized tonic-clonic seizures and is poorly controlled by or resistant to medical treatment. The mother of the two patients, also a carrier of ring (20) chromosomal mosaicism, was clinically and phenotypically normal and did not exhibit any signs of epilepsy. Lymphocyte and fibroblast cultures from the most severely affected sib, the proband, contained the highest percentage of cells with ring (20) chromosome and revealed the greatest instability of the ring. Though it is assumed that the ring (20) chromosome arose from terminal breakage and reunion in both arms, no loss of genetic material could be documented cytogenetically. Yet the question arises of how ring chromosomal mosaicism can be passed on. One explanation might be that a chromosome 20 predisposed to terminal lesions or breaks is transmitted from the mother to her offspring. Inherited instability of this type might lead to de novo formation of the ring.

Inherited ring chromosomes: an analysis of published cases

“…Although transmission of a ring chromosome from parent to offspring may account for its inheritance, an alternative mechanism can also be inferred from the fact that in 9 families both the parents and the offspring had normal cells in addition to the ring cells. This familial ring chromosome mosaicism suggests an inherited instability of the chromosome involved leading to de novo reformation of the ring in the second generation (Zdansky et al 1969;Stoll and Roth 1983;Back et al 1989). The presence of a normal cell line in an offspring with a ring, born to a ring carrier, supports the conclusion that in some instances it is a chromosome predisposed to terminal deletion that is transmitted from the parent to the offspring rather than a ring per se.…”

“…The review of case reports revealed 30 individuals with a ring (plus two fetuses detected at prenatal diagnosis) who were the offspring of a total of 23 transmitting parents (Back et al 1989;Bowser Riley et al 1981;Burden et al 1973;Christensen et al 1970;Dallapiccola et al 1980;Donlan and Dolan 1986;Fagan et al 1988;Fryns and Van den Berghe 1979;Fujimaki et al 1987;Hertz 1987;Howell et al 1984;Ikeuchi et al 1990;Kennerknecht et al 1990;Kosztolfinyi et al 1985;Matalon et al 1980;Matsubara et al 1982;Miller et al 1987;Palmer et al 1977;Schmidt et al 1983;Stoll and Roth 1983;Zdansky et al 1969). …”

Cognitive Impairment and Abnormal Behaviour Related to Ring Chromosome 20 Aberration

“…Whereas these findings argue for a sporadic origin of r(20) with regard to the limiting fact of missing parental karyotype data Giardino et al (2010) performed genetic investigations in 8 patients with r(20) syndrome together with available parents and found one case with inherited r(20). Heredity transmission was also reported to be present in three other families (Canevini et al 1998;Back et al 1989;Herrgard et al 2007). Giardino et al (2010) declare that r(20) mosaicism represents generally a de novo event suggesting that not r(20) itself is inherited but an instable chromosome 20 with a disposition to form r(20) (Back et al 1989).…”

Chromosomal Abnormalities and Epilepsy: A Review for Clinicians and Gene Hunters

“…More than 30 cases of epilepsy associated with ring chromosome 20 have been reported (194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207). The locus of fusion between the deleted long and short arms in ring chromosome 20 in 12 cases was one of p13q13, p13q13.3, or p13q13.33.…”

“…Interictal EEG often shows focal epileptiform transients from frontal or temporal regions. The characteristic finding is of long runs of bilateral high-amplitude slow wave with or without a spike component, with a bifrontal predominance (195,196,199,200,202,(206)(207)(208)(209).…”