Xq21.1q21.31 Duplication in Two Male Siblings

Abstract

Despite the increased use of array comparative genomic hybridisation, duplications of Xq remain rarely reported in the literature. Xq21.1q21.31 duplication has previously been reported only once in a boy with features of Prader Willi syndrome (PWS). We report 2 malesiblings with maternally inherited duplication of Xq21.1q21.31 who demonstrate a variable phenotype. The proband has Prader Willi-like features such as global developmental delay, autism, obesity, short hands, and small genitalia with a history of food seeking behaviour, while his younger brother has isolated speech delay with some autistic features under evaluation. Both siblings have features such as bitemporal narrowing and small hands. It is therefore likely that the phenotype of duplications in this region is broader than PWS phenocopy, and further cases would be required to elucidate this.

Keywords: Array CGH; Autism; Dysmorphic facial features; Microduplication syndrome; Xq21.1q21.31 duplication.

Fig. 1

The physical appearance of the proband at 11 years old demonstrating bitemporal narrowing, elongated face, large earlobes, thin upper lip, and central obesity (a, b). Short hands with short fingers (c), and an increased sandal gap and slightly elongated broad first toes are shown (d). The proband's brother at 6 years old with bitemporal narrowing and depressed nasal bridge (e, f).

Fig. 2

Xq21.1q21.31 duplication found in the proband and his brother. Area of interest is shown in the highlighted area, GRCh37 Xq21.1q21.31(82857739_86848989). Genes included in the duplicated segment APOOL, CHM, CYLC1, DACH2, HDX, KLHL4, POF1B, RPS6KA6, SATL1, and ZNF711. Duplicated area reported by Gabbett et al. [2008] highlighted with arrows in red, minimum region 11.14 Mb GRCh37 Xq21.1q21.31(76755905_87898537), maximum region 14.14 Mb GRCh37 Xq21.1q21.31(76158932_90295428).