Molecular cytogenetic characterization of an inherited maternal duplication 20p11.21p13 associated with a small 20p11.21 deletion

Abstract

Partial trisomy for the short arm of chromosome 20 is a relatively rare chromosomal abnormality. Most cases are derived from reciprocal translocations with the presence of partial monosomy of other chromosomes, and thus it has been difficult to delineate a specific phenotype [review in Chaabouni et al., 2007]. The molecular cytogenetic characterization of chromosome 20p rearrangements has been described in a few cases, which has allowed not only a more accurate genotype–phenotype correlation, but also the investigation of its underlying mechanisms. Sidwell et al. [2000] reported on a case of pure trisomy 20p arisen from de novo isochromosome formation, and associated with a non-reciprocal rearrangement involving the translocation of 20q11.1qter sequences onto chromosome 4p. Ravel et al. [2003] described a de novo isolated interstitial tandem duplication of chromosome 20p12 with no evidence of repeated sequences mediating this rearrangement. Ardalan et al. [2005] reported on a derivative with 20pter duplication and 20qter deletion originated from a familial pericentric intrachromosomal insertion following homologous pairing and crossover at meiosis. Chaabouni et al. [2007] described a case of de novo duplication spanning almost the whole short arm of chromosome 20p and associated with a small distal 20q deletion. Recently, Leclercq et al. [2009] reported on the first case of inversion duplication deletion involving the short arm of chromosome 20p (inv dup del 20p), which likely formed through a U-type exchange. High-resolution oligonucleotide CGH array revealed an 18.16 Mb duplication of 20p11.22p13 in association with a 20p13 terminal deletion sizing 2.02 Mb. Herein, we report on a case of trisomy 20p of maternal origin initially detected by conventional cytogenetic investigation. Molecular cytogenetic studies with fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) array revealed a direct tandem duplication of 20p11.21p13 associated with a contiguous 20p11.21 proximal microdeletion. The clinically normal mother had the same chromosome abnormality detected in about 15% of her lymphocyte cells. We have compared the phenotype of our patient to similar cases from the literature in order to further delineate trisomy 20p syndrome. The patient, a 21-year-old woman (Fig. 1), was the first child of non-consanguineous normal parents, aged 23 (mother) and 22 years (father). The mother had two miscarriages at 10 weeks of gestation and a normal son was subsequently delivered. Patient’s pregnancy was uncomplicated and she was delivered at term by caesarean. Apgar scores were 6 and 8 at 1 and 5 min, respectively. Birth weight was 2,960 g ( 10th centile) and birth length 49 cm (25th centile). The sucking reflex was present. At 2 months she had surgery for bilateral inguinal and umbilical hernia. By the age of 9 months she had little control over her head and neck and could not sit without support. She started walking at the age of 18 months with frequent falls. Independent walk was achieved at 2 years of age. On examination at 21 years of age, occipital-frontal circumference (OFC) was 54 cm (2–50th centile), height 1.70 m (90th centile) and weight 65 kg (75–90th centile). She had a high forehead, hypertelorism, downslanted palpebral fissures, deep-set eyes, thick