Identification, counselling, and outcome of two cases of prenatally diagnosed supernumerary small ring chromosomes

Abstract

De novo supernumerary small ring chromosomes have mainly been reported in pediatric patients with clinical abnormalities, thus, there may be bias of ascertainment. Reports on prenatally diagnosed cases with postnatal follow-up are rare. With the availability of chromosome specific alpha-satellite centromeric probes, the interest in these previously unidentifiable supernumerary small ring chromosomes has been rekindled [Callen et al.: J Med Genet 27: 155-159, 1990; Callen et al.: Am J Hum Genet 48:769-782, 1991; Callen et al.: Am J Med Genet 43:709-715, 1992]. We report on 2 prenatal diagnosis cases, where a ring was noted in 25 and 60% of the amniocytes, respectively. The initial G- and C-banding in Case 1 allowed an assumption of a chromosome 1 origin of the extra chromosome. This was confirmed by fluorescence in situ hybridization (FISH) studies using the appropriate probes. No similar initial assumption could be made in Case 2; thus, random trials with multiple probes were performed. A chromosome 19 origin in Case 2 was eventually concluded. The large amount of C-band positive material on the extra chromosome and the normal level 2 fetal ultrasound examination suggested a favorable outcome in both cases, but the possibility of mental retardation could not be ruled out. An empiric risk figure with regard to prenatally diagnosed de novo supernumerary small ring chromosomes is not available. Although the decision making processes of the parents were different, they both decided to continue the pregnancy. At age 9 months and 1 1/2 years both children, a girl and a boy, showed normal growth and development.

Pure trisomy 19p syndrome in an infant with an extra ring chromosome

“…To the best of our knowledge, only five cases (including identical twins) have been reported (Quack et al, 1992;Michalski et al, 1993;Ghaffari et al, 1998;Vaz et al, 1999;Shahwan et al, 2004;see Table 1). In two subjects and in the twins, the origin of the extra ring from chromosome 19 was proved, either using a specific centromeric probe (Michalski et al, 1993) or chromosome 19 paint (Vaz et al, 1999;Shahwan et al, 2004). In both cases no attempt was made to characterize further the amount of 19p and/or 19q material included in the marker.…”

Characterization of the first supernumerary tricentric ring chromosome 1 mosaicism by conventional and molecular cytogenetic techniques

“…Even though only 8 % of the cells showed the presence of the marker chromosome, in which the content of the euchromatic part 1q21 is fivefold instead of twofold mimicking a 24 % mosaicism for partial trisomy 1q10q21, the aberration was detectable by CGH using narrow thresholds. So far, 19 cases of "pure" SMCs derived from chromosome 1 containing different pericentric euchromatic parts of 1p and/ or 1q have been described (Callen et al, 1990(Callen et al, , 1991(Callen et al, , 1999Michalski et al, 1993;Plattner et al, 1993;Chen et al, 1995;Lanphear et al, 1995;Crolla et al, 1998;Levy et al, 1998;Xu et al, 1998;Giardino et al, 1999;Anderlid et al, 2001;Dawson et al, 2001;Finelli et al, 2001;Röthlisberger et al, 2001;Tönnies et al, 2003). Regarding the size of the ring chromosome and the content of euchromatic material from proximal 1q, only four of the supernumerary ring 1 chromosomes reviewed in the literature are cytogenetically comparable (cytogenetically matching cases: Chen et al, 1995;Xu et al, 1998;Giardino et al, 1999;Finelli et al, 2001; see also Table 1).…”

“…Therefore, the precise identification and characterization of a marker chromosome and its euchromatic content is of essential importance in genetic counseling and diagnosis. So far, 19 cases of single SMCs derived from chromosome 1 containing different euchromatic parts of proximal 1p and/or 1q have been described (Callen et al, 1990(Callen et al, , 1991(Callen et al, , 1999Michalski et al, 1993;Plattner et al, 1993;Chen et al, 1995;Lanphear et al, 1995;Crolla et al, 1998;Levy et al, 1998;Xu et al, 1998;Giardino et al, 1999;Anderlid et al, 2001;Dawson et al, 2001;Finelli et al, 2001;Röthlisberger et al, 2001;Tönnies et al, 2003). We report here a 3.5-year-old girl referred for cytogenetic analysis because of language and motor delay who has a tricentric supernumerary ring chromosome 1 characterized by molecular cytogenetic techniques including YAC-FISH, chromosome microdissection followed by FISH, microsatellite analysis and CGH.…”

Small supernumerary marker chromosomes (sSMC) in humans

“…Singular studies with in summary confusing results can be found in e.g. Viersbach et al (1997), case 1; Anderlid et al (2001), case N; Batista et al (1995); Michalski et al (1993), case 2; Felbor et al (2002), case 2 (for overview see http://mti-n. mti.uni-jena.de/Fhuwww/MOL_ZYTO/sSMC.htm).…”