Radiographic Atlas of Skeletal Development of the Hand and Wrist

Analysis of 207 case reports on patients with ring autosome showed that: (1) Forty patients, a fifth of the total, had extreme growth failure together with an otherwise almost-normal appearance, viz. no major malformation, no specific deletion syndrome, no or only a few unspecific minor anomalies. This phenotype may be regarded as the “ring syndrome”, a term proposed by Cote et al. (1981) since it is independent of what chromosome is involved. (2) Severe growth failure, the sole major physical abnormality in the “ring syndrome”, was seen significantly more often among patients with ring of larger chromosomes than among patients with a smaller ring, indicating that the greater the chromosome involved in ring formation, the higher is the probability of severe growth failure. (3) Larger ring chromosomes showed significantly more often instability than smaller rings, suggesting that there may be a correlation between ring instability and the size of the chromosome involved. (4) Growth failure was present in significantly more patients with a “labile” ring than with a “stable” ring, indicating that a correlation may exist between ring instability and growth failure. It is suggested that the “ring syndrome” observed in many cases with ring autosome may result from end-to-end fusion of chromosome ends, an event not involving deletion in the genetic sense. It is also suggested that the “ring syndrome” is caused by a continuous generation of secondary aneuploid cells with increased mortality, i.e. structural ring instability which seems to be a function of the size of the chromosome involved. Thus, formation of a ring chromosome in certain cases might be regarded as a “structural mutation”, i.e. an alteration in the structure of the genetic material per se, rather than a loss or gain of genetic dosages.

Does "ring syndrome" exist? An analysis of 207 case reports on patients with a ring autosome

Gene dosage effects for soluble isocitrate dehydrogenase (IDH1) were investigated in four unrelated cases with abnormalities involving the long arm of chromosome 2. Case 1 was trisomic for 2q33.3→qter, Case 2 monosomic for 2q33.3→q35, Case 3 trisomic for 2q11.2→q24.2, and Case 4 monosomic for 2q23→q24.2. These abnormalities were de novo except in Case 1, where trisomy 2q resulted from a maternal translocation. The red cell IDH1 levels were significantly reduced in Cases 1 (41.4% of normal value) and 2 (51.9%), while they were normal in Cases 3 and 4. The low IDH1 level also in the father of Case 1 (43.6%), together with the common electrophoretic phenotype of IDH1 in red cells as well as leukocytes, led us to suppose that Case 1 was really heterozygous for common and probable null alleles, and that the IDH1 gene locus could be excluded from 2q33.3→qter. On the other hand, normal IDH1 values in the parents of Case 2 were consistent with the hemizygosity for this locus in Case 2. The results suggested that the IDH1 locus could be assigned to the 2q33.3 band, especially the proximal portion of it.

Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3.

Three children with deletions of the terminal portion of the long arm of chomosome 2 [del (2) (q37)] are described and their clinical findings compared to published cases of 2q terminal deletions. Common clinical findings include development delay, macrocephaly, frontal bossing, depressed nasal bridge and cardiac anomaly. Hypotonia and repetitive behavior are also seen during different times of development. The facial characteristics of children with 2q terminal deletions are not uniform, but development delay is a constant finding. Chromosomal analysis of such children using high resolution banding may uncover the diagnosis of a small chromosomal deletion.

Clinical phenotype associated with terminal 2q37 deletion

We report on an infant with multiple congenital anomalies including complex craniosynostosis associated with an unbalanced karyotype, 46,XY,-2,+der(2),t(2;15)(q37;q26)pat The previous report of a child with cloverleaf skull and partial duplication of 15q25----qter and the Man-on-Mouse Homology map suggests that a critical segment for synostosis of sutures may be in this region

Craniosynostosis associated with partial duplication of 15q and deletion of 2q.

A new case of ring chromosome 2 is described and compared with the five cases hitherto reported. The clinical picture includes a severe pre- and postnatal growth failure, microcephaly, psychomotor retardation, and some minor dysmorphic features. Cytogenetic studies revealed a ring 2 structure and aneuploidy. Banding analysis failed to demonstrate a substantial loss of chromosomal material. Enzymologic studies revealed a decrease of red cell acid phosphatase activity suggesting the localization of its gene in the 2p25→2pter region.

M. Jansen

Papers

Ring chromosome 2: clinical, chromosomal, and biochemical aspects.