| Objective:Cri-du-Chat syndrome (CDCS) is one of chromosome deletion syndrome caused by a partial deletion of the short arm of chromosome5, also called5p-syndrome or5p monosomy, is one of the most common chromosomal deletion syndrome. The main clinical feature of typical CDCS including a high-pitched monochromatic cat-like crying that usually disappears in the first year of life, a rounded face, wide-set eyes, low-set ears, micrognathia, high-arched, low birth weight, severe mental retardation, hypotonia and congenital heart disease, severe malocclusion, and other complex symptoms.The karyotype of CDCS including a de novo5p terminal deletion, a de novo5p interstitial deletion, a de novo translocation, familial translocation and other rare complex abnormalities. Because of the complexity of the clinical feature and diversity of karyotype, CDCS is remains poorly understood and there is no protective measure for CDCS. In order to improve the comprehension, diagnosis and prevention of CDCS, we collected17CDCS family, using molecular cytogenetic techniques to confirm the karyotype of CDCS cases and using SNP-array technology detect nine CDCS cases, and analyzing the relationship of the chromosome deletion region and the clinical feature. Their clinical data were retrospectively reviewed and the condition of pregnancy were emphatically analyzed to explore whether the routine monitoring of early warning pregnancy of CDCS. Prenatal diagnosis were performed on the6pregnant had given birth CDCS case to analyze the risk of recurrence of CDCS.Methods:G-banding karyotype was performed to analyze17CDCS case and their parents. M-FISH with Cri-du-Chat Syndrome region probe as well as subregional probes mapping to5pter,5qter were performed in the cases and their parents. We used SNP-Array technology for whole-genome analysis on9CDCS cases. A retrospective study was performed for pregnancy condition of17families CDCS fetus. Amniotic fluid cells were obtained by amniocentesis for prenatal diagnosis.Results:The karyotype analysis showed that13cases of CDCS had5p terminal deletion characterized by simple short arm. Two cases carry a derivative chromosome5from the5p and18p translocation and one case carry a derivative chromosome5derived from5p and11q translocation. Pericentric inversion with terminal deletion of chromosome5was detected in one case. Molecular cytogenetic analysis showed that15cases had new mutations and2patients had maternal reciprocal translocation. All CDCS cases had5p terminal deletion without interstitial deletion.9cases detected by SNP-arrays had different breakpoint and one of them was a de novo5p partial deletion and cryptic18p duplication, the variation can not be detected by G banding due to its smaller fragments. Retrospective analysis of above-mentioned17CDSC case, no abnormality prenatal screen results was found, no specific indications was found except intrauterine growth retardation during fetus period. When four couples with normal karyotype were going to pregnant, amniotic fluid cell culture results showed that the fetal karyotype was normal; two translocation carrier family, the amniotic fluid prenatal diagnosis showed one case was maternal balanced translocation carriers, while another case of carryed maternal derivative chromosome5and its birth will be the CDCS patients.Conclusion:The terminal deletion is the main type of CDCS. The recurrence risk of CDCS is closely related to the karyotype of patients and their parents, if parents were normal, the recurrence risk is extremely low, they can choose natural pregnancy with prenatal diagnosis; if one parent was a translocation carrier, then the recurrence risk of natural pregnancy was high, PGD may be an ideal choice. |
