A familial rearrangement(3;5;9) with paternal and maternal transmission leading to a duplication 3p/deletion 5p infant

We report a complex rea(3;5;9) observed in an unbalanced child who inherited this mutation from his mother and maternal grandfather. The propositus, a male infant, was the only child of healthy non-consanguineous parents aged 28 (father) and 24 years. There was no history of miscarriages or malformations on either side of the family. The pregnancy and vaginal delivery were normal. The infant’s birth weight and length were 2,450 g and 45 cm, respectively. Due to a complex heart defect (PDA, VSD, and ASD) and respiratory insufficiency, he was hospitalized for 30 days. Two months later, he underwent surgery to correct the cardiac defects. His psychomotor development was delayed. Clinical examination at 6 months of age revealed severe growth retardation (weight of 4.9 kg, length of 58 cm, OFC of 37 cm), hypotonia, diminished reflexes, brachycephaly, prominent forehead, bilateral ectropion and blepharophimosis, a small nose with anteverted nares, microstomia, micrognathia, a short neck, dysplastic and cupped ears, an osseous appendix in the sternum, and a single palmar crease in the left hand. The abdomen and external genitalia were normal. The patient had neither a cat-like cry nor telecanthus. One month later, the patient died of hypoventilation; no autopsy was performed. The karyotypes of the patient and several relatives were determined using G-banding and Fluorescence in situ hybridization (FISH). The probes 3p (Vysis, Abbott Laboratories, Abbott Park, IL, USA)/5p (Cytocell, Cytocell Ltd., Cambridge, UK) subtel, ABL/BCR (Vysis, Abbott Laboratories, Abbott Park, IL, USA), and cri du chat/Sotos (Cytocell, Cytocell Ltd., Cambridge, UK) were used to test both the child and his mother; the mother was also tested with painting probes for chromosomes 3 and 9 (Cytocell, Cytocell Ltd., Cambridge, UK). This combined analysis led to the diagnosis of a familial 4breakpoint rea(3;5;9) in both balanced and unbalanced forms (Figures 1 and 2). The patient had a duplication for 3p24.3Rpter concomitant with a deletion for 5p15.2Rpter due to a 46,XY,der(5)der(9)rea(3;5;9)(p24;p13.1p15.2;q22)mat.ish der(5) (5psubtel–,cri du chat–,ABL+)der(9)(3psubtel+,5psubtel–,ABL–) karyotype. In contrast, the mother9s balanced complement was 46,XX,rea(3;5;9)(3qterR3p24.3::5p15.2R5pter;5qterR5p13.1:: 9q22R9qter;9pterR9q22::5p13.1R5p15.2::3p24.3R3pter).ish der(3)(3psubtel–,5psubtel+,cri du chat+)der(5)(5psubtel–,cri du chat–,ABL+,wcp9+)der(9)(3psubtel+,cri du chat–,ABL–, wcp3+). The patient’s maternal grandfather was also a balanced carrier, and the patient’s father had a normal 46,XY karyotype. The non-specific phenotype of the patient, including the lack of the cry and facies characteristic of the 5p deletion syndrome, can more parsimoniously be ascribed to his compound imbalance (1). The complex heart defect and death in infancy appear to be related to the 3p duplication (2). Because the 5p segment can be regarded as ‘‘inserted’’ into the der(9), our observation may support the contention that complex chromosome rearrangements (CCR) with at least one insertional translocation can be transmitted either paternally or maternally and are refractory to recombination