Cri-du-Chat Syndrome Cytogenetically Cryptic Recombination Aneusomy of Chromosome 5: Implications in Recurrence Risk Estimation

• Published in: Molecular syndromology Vol. 1; no. 2; pp. 95 - 98
• Main Authors: Ohnuki, Y., Torii, C., Kosaki, R., Yagihashi, T., Sago, H., Hayashi, K., Yasukawa, K., Takahashi, T., Kosaki, K.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-01-2010
• Subjects: Short Report; Trisomy 5q; Monosomy 5p; Genetic counseling
• ISSN: 1661-8769; 1661-8777
• DOI: 10.1159/000319321

Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry. Most cri-du-chat syndrome cases result from a sporadic de novo deletion that is associated with a low recurrence risk. On rare occasions, however, cri-du-chat syndrome with 5p monosomy can be accompanied by 5q trisomy. This combination is virtually always associated with parental large pericentric inversions. Among previously reported cri-du-chat syndrome cases with 5p monosomy accompanied by 5q trisomy, the aneusomy of chromosome 5 in all but one case was cytogenetically visible using G-banding. When an accompanying 5q trisomy is detected, a significant recurrence risk is expected. We here report on a patient with cri-du-chat syndrome phenotype who initially exhibited a normal karyotype on G-banding but in whom molecular analysis using multiplex ligation-dependent probe amplification and array comparative genomic hybridization revealed a 5p deletion accompanied by a 5q duplication. Parental chromosomal testing led to the identification of a very large pericentric inversion, of which breakpoints resided at the terminal regions of 5p15.31 and 5q35.1. This information was vital for counseling the family regarding the significantly high recurrence risk.