Three Offspring with Cri-du-Chat Syndrome from Phenotypically Normal Parents

Abstract

Cri-du-chat syndrome is characterized by facial dysmorphism, intellectual disability, and multiple congenital anomalies. Most cases occur de novo. Here, we report 3 siblings with cri-du-chat syndrome born to healthy parents. The proband was admitted to our clinic at the age of 6.5 years due to severe intellectual disability, facial dysmorphism, and heart defect. His karyotype showed a deletion of chromosome 5p. Microarray analysis revealed a 29-Mb deletion in chromosome 5p and a 4.7-Mb duplication in chromosome 19q. FISH analysis indicated an unbalanced translocation between 5p13.3 and 19q13.4. During follow-up, the second and the third child of the family were born with the same chromosome abnormality. Parental peripheral blood and skin fibroblast karyotypes as well as the FISH results using chromosome 5p- and 19q-specific subtelomeric probes were normal. FISH analysis of the father's sperm detected a 5p deletion in 12.8% of 200 cells, and microarray analysis confirmed the same unbalanced chromosome abnormality in a mosaic pattern. Uncultured peripheral blood and buccal smear of the father were also studied by FISH to exclude low-level mosaicism and in vitro culture effect. This is the first study that provides molecular evidence of paternal gonadal mosaicism of an unbalanced translocation detected in 3 siblings with cri-du-chat syndrome.

Caracterização citogenêmica da deleção do braço curto do cromossomo 5

“…A maioria dos casos (80-90%) de portadores da SCDC é de rearranjos genômicos de novo, mas em cerca de 10-15% os rearranjos são herdados de translocações balanceadas de um dos pais, preferencialmente de origem paterna. Em menor frequência, a SCDC ocorre por rearranjos cromossômicos complexos, como anéis e inversões (Niebuhr, 1978;Mainardi et al, 2001;Mainardi et al, 2006) e ainda de forma mais rara, pode ocorrer pela presença de uma baixa porcentagem de células contendo rearranjos em 5p em mosaicismo gonadal (Alkaya et al, 2020).…”