Four new cases of ring 21 and 22 including familial transmission of ring 21.

Abstract

SUMMARY Four new cases of ring G chromosomes are presented including one family in which the ring 21 is present in a mother and in her daughter, who has 47,XXX,r(21) chromosomes. The clinical and dermatoglyphic findings in r21 and r22 syndromes are reviewed.G-deletion syndromes are associated with various cytogenetic findings. These include complete monosomy, monosomy-mosaicism, partial deletion of the long arm of a G group chromosome or mosaicism for such a deletion, translocation, or ring G chromosomes.While some of the translocations resulting in unbalanced segments with G-deletion syndrome have been familial the only evidence suggesting transmission of a ring G from parent to child occurred in a family with chromosome instability and mosaicism (Zdansky et al, 1969). In this paper we present the unusual finding of familial r21 in a mother and child. The daughter also carries an extra X. Two other cases of ring G are presented, one r21 and the other r22. These 4 individuals with ring G identified in banded chromosomes have given us the opportunity to review the literature of G deletion syndromes in which the chromosomes have been clearly identified by one of the several banding procedures. We have not included those cases resulting from translocations since such individuals may also carry an excess of genetic material derived from the translocation partner.Since there are diverse cytogenetic findings in the G-deletion syndromes it is not unexpected that the clinical picture also varies. Warren and Rimoin (1970) described two separate clinical entities, the Gl and G2 deletion syndromes and related them to deletion of chromosomes 21 and 22, respectively . Our work confirms the existence of two syndromes while pointing out the hazards of making the diagnosis on phenotype alone or even when nonbanded chromosomes indicate a G-deletion. Case reports Case 1 Family 21209This proband was a 6-day-old white girl, born to 27-year-old parents. The birthweight was 3090 g, occipital-frontal circumference (OFC) 38 cm (>97th centile), length 51 cm (75th centile). Clinical findings included: preauricular pits, hypoplastic mandible, simple vermillion border with long, flat philtrum, wide open metopic suture, high scalp hair, intact but high, narrow palate, grade 1-2/6 systolic ejection murmur along the left stemal border, palpable pole of the left kidney, thumbs heldunderthe fingers and upperextremities flexed, hyperextensible joints, stiff legs, bilaterally dislocated hips, hypolastic toenails, marked hypotonia, and wide spaced nipples. There was microphthalmus of the right eye and smooth cysts on the lower lids. The murmur was thought to be consistent with persistent ductus arteriosus. X-ray examination showed a small mandible, the superior mediastinum widened secondary to an enlarged thymus gland, ribs and bones of the hands and feet thin and fragile, and lateral malpositioning of both femoral heads in relation to the acetabulum with normal acetabular angles bilaterally. The

Ring chromosome instability evaluation in six patients with autosomal rings

“…Some researchers found higher frequencies of monosomic cells without the ring chromosomes in fibroblast compared to lymphocyte cultures (Sparkes et al, 1967;Moore et al, 1973;Palmer et al, 1977;Peeden et al, 1983), while others found no significant differences between the two tissues (Valente et al, 1977;Ledbetter et al, 1980;Manouvrier-Hanu et al, 1988). Ledbetter et al (1980), however, found ring chromosomes 15 with an abnormal morphology in 9% of metaphase cells from lymphocyte cultures and in 20 and 24% of cells from fibroblast cultures in the third and tenth subculture, respectively, although it was not possible to know if these cells were formed de novo or were perpetuated in a clonal manner.…”

“…Thus, a cryptic deletion may be the basis of the phenotypic abnormalities in apparently complete rings, such as the deletion of the IGF1R gene at 15q26.3 in a ring 15. Also, the phenotypic variability seen in patients with similar ring chromosomes may be a consequence of their instability and of the variation in gene dosage of each cell (Hecht, 1969;Palmer et al, 1977;Zuffardi et al, 1980;Knijnenburg et al, 2007;Rossi et al, 2008a), as for instance in the patient with a ring 18 reported by Koç et al (2008) who showed partial trisomy 18 in a considerable number of cells, due to the formation of dicentric rings, which resulted in a more severe phenotype. Rossi et al (2008a) described a patient with a ring 13 who had a deletion and a duplication of approximately 6 Mb each, oligohydramnios and cystic kidney, features that were attributed to trisomy 13.…”

Molecular mechanism in the formation of a human ring chromosome 21.

“…Most ring chromosomes arise de novo, yet occasional familial transmission has been reported (2)(3)(4)(5). The frequency of ring chromosomes is 1 in 25,000 recognized conceptions (6), and all human chromosomes have been observed as rings.…”

Determination of the breakpoints and the parental origin of a ring 22 chromosome: An analysis by high-resolution banding technique, quinacrine and silver stainings

“…Findings recognized in 10 to 50% of the patients are feeding difficulty, short stature, abnormal cranium, maxillary hypoplasia, hypertelorism, ptosis of eyelids, low-set ears, low nasal bridge, micrognathia, high-arched palate, vertebral anomaly, brachydactyly, syndactyly (finger), hypertonia, seizures, arch dermal ridge pattern and radial loop pattern (Table 1) (Palmer et al, 1977;Aller et al, 1979 and present case). Mosaicism of r(22) with 22 monosomy was highly dominant in most of the cases.…”

“…Since Hunter et aL (1977) reviewed clinical features of r(22) syndrome on 21 cases, additional 17 cases have, to our knowledge, been reported including the present case (Palmer et al, 1977;Howard-Peebles, 1977;Funderburk et al, 1979;Faed et al, 1979;Fryns et al, 1979;Aller et aI., 1979;Sakuragawa et al, 1979;Fowler et al, 1980;Kondo et al, 1980;Stoll and Roth, 1983;Reeve et al, 1985). As mentioned by Funderburk et al (1979), there is considerable variability in its expression from normal mentality to profound mental retardation with multiple minor anomalies.…”