Characterization of a complex chromosomal rearrangement in a patient with a typical catlike cry and no other clinical findings of cri-du-chat syndrome

Abstract

We report on the clinical, cytogenetic, and molecular cytogenetic findings in a 4-year-old girl who was evaluated for developmental delay and a catlike cry from birth. No other findings of cri-du-chat syndrome were present. Karyotype analysis demonstrated a de novo deletion and inverted duplication of the 5p region. The abnormality was confirmed and further defined by detailed FISH analysis using cosmid and lambda phage clones previously mapped to distinct regions of 5p. The analyses documented deletion of 5p15.3-->pter and an inverted duplication of 5p14-->5p15.3. The deleted segment on 5p contains the region implicated in the isolated catlike cry feature of the cri-du-chat syndrome, confirming that the genes involved in the catlike cry map to the distal end of 5p. Except for the catlike cry and possibly the developmental delay that may be due to the deletion of 5p, the duplication of 5p14-->5p15.3 in this patient did not present with additional anomalies. This study further demonstrates the usefulness of the molecular cytogenetic approach for characterizing complex chromosome rearrangements. Such analyses of patients with an isolated catlike cry can avoid an incorrect diagnosis of the cri-du-chat syndrome, which is associated with a more severe prognosis.

A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5

“…A varied clinical manifestation was also observed in patients with Trisomy 5p, depending on the position of the duplication [7,8]. Duplications involving complete 5p or a small segment between 5p10-5p13.1 usually manifest in a more severe phenotype; thus, this region was proposed to be the critical region for Trisomy 5p [9-11].…”

“…A combination of terminal deletion and inverted duplication of 5p is infrequent in literature. To the best of our knowledge, only six patients have been reported so far [8,13-17]. Consequences of these uncommon chromosomal rearrangements differ, depending on the size of the deletion and duplication in each particular case.…”

“…Consequences of these uncommon chromosomal rearrangements differ, depending on the size of the deletion and duplication in each particular case. This is shown in variable clinical pictures observed, although authors mainly describe deletion as causative for the clinical outcome [8,13,16,17]. …”

A Familial Cri-du-Chat/5p Deletion Syndrome Resulted from Rare Maternal Complex Chromosomal Rearrangements (CCRs) and/or Possible Chromosome 5p Chromothripsis

“…Less than 5% of the patients have de novo translocations or other rare chromosomal aberrations such as complex chromosomal rearrangements (CCRs) [8], [9]. About 10%–15% of the 5p deletions result from unbalanced segregation of a parental balanced rearrangement such as translocation or inversion [10], but very rarely from a balanced parental insertion [11] or CCRs [12].…”

Inverted duplications: how many of them are mosaic?

“…The best-known case is that of the inv dup(8p). 1,2 Other examples are those concerning 1q, 3,4 2q, 5 3p 6,7 4p, 8 5p, 9,10 9p, 11 10p and 10q, 12 18p 13 18q, 14 21q 15 and the X;X or the Y;Y rearrangements leading to duplications of parts of the short or the long arm with concomitant deletion. 16 It has been assumed 1,5 that the first product of the abnormal meiotic recombination on the basis of this type of rearrangement was a dicentric chromosome, either p-qHq-p or q-pHp-q.…”