Apparently non‐deleted ring‐1 chromosome and extreme growth failure in a mentally retarded girl

Abstract

A girl, who was the product of the first recognized conception by healthy and chromosomally normal parents, and who was born 5 weeks before term with a birth weight of only 1,690 g, was found to have a ring‐1 chromosome, r(1), in almost all cells analysed. A minor proportion of cells had a normal diploid chromosome complement including two regular No. 1 homologues. A few cells contained a large dicentric ring, and two monocentric ring‐1 chromosomes were simultaneously observed in a few other cells. Q‐ and G‐banding revealed the r(1) chromosome to be apparently non‐deleted. The patient phenotypically resembled the three previously described human subjects with r(1) chromosomes, especially with respect to her remarkable growth failure and mental retardation. From consideration of data available on general development in subjects with an autosomal ring chromosome, it appears likely that the presence of such a ring chromosome per se in an early foetal chromosome complement may predispose to significantly retarded intrauterine and postnatal growth. Various genetical implications, including mitotic irregularities with subsequent loss of cells at division, are thought to account for the significant reduction of body mass in these patients.

Phenotypic variation in two patients with a ring chromosome 22

“…If present throughout many tissues, this might explain her more severe phenotype, although mitotic loss of the ring chromosome may have occurred late in somatic development, therefore having little effect on major organogenesis, or it could even have occurred artifactually during cell culture. Otherwise there was no evidence for differing behavior of the ring chromosome 22 in somatic cells from the two patients, since neither dicentric rings nor cells with two ring chromosome 22's were observed, as was recently reported in ring-1 chromosome patients with differing phenotypes (Kjessler et al 1978). The differing phenotypes observed in the two patients reported here may have resulted from some as yet poorly understood mechanism, just as the wide variability of developmental rate in Down syndrome children remains unexplained (Melyn & White 1973).…”

A patient with constitutional ring 1 chromosome characterized by SNP array CGH

“…There is a long‐standing debate as to whether the phenotype in individuals with ring chromosomes is attributed to a “ring syndrome” due to mitotic instability or to the loss of specific genes due to formation of the ring chromosome . Because dwarfism is reported in individuals with ring 1 chromosome (and other ring syndromes), but not in patients with 1q43q44 deletion, we suspect that our patient's significant growth retardation is the result of the former, as this would not be entirely explained by his 1q43q44 deletion.…”

“…Constitutional ring chromosomes are a rare cytogenetic abnormality found in humans believed to form by deletion and subsequent fusion at the telomeres. In addition to deleted genomic material, the instability of the ring structure itself may contribute to an abnormal phenotype, specifically growth failure . It has also been suggested that larger ring structures are more labile and result in more severe growth retardation than smaller rings .…”

“…It has also been suggested that larger ring structures are more labile and result in more severe growth retardation than smaller rings . While ring structures have been reported in various autosomes, only six patients with constitutional ring 1 chromosome have been reported to date . The oldest reported individual lived to be at least 12 years of age .…”

The level of 6‐phosphogluconate dehydrogenase (6‐PGD) activity in a patient with a 1p terminal deletion suggests that the gene locus is not distal to sub‐band p36.3 on chromosome 1

“…Unfortunately, the likely loss of chromosomal material from 15q in each of these cases precludes definitive analysis of the phenotypic effects of the l p deletion. Similar confounding factors complicate case reports of several ring 1 chromosomes (which necessarily involved terminal deletions of lq as well as lp) which displayed growth failure with mental retardation (Kjessler et al 1978, Bobrow et al 1973, Wolf et al 1967, Gordon & Cooke 1964. Yunis et al (1981) reported on a 4-yearold patient with severe growth and mental retardation and multiple anomalies including enophthalmos and abnormal EEG.…”