54 - The Clinical Spectrum Associated With Xq25q26 Duplications: A Report of Two Novel Duplications and Review of the Literature

Abstract

Interstitial microduplications involving Xq26 are relatively rare with only twelve patients (seven males and five females) described in the literature. We report two families with inherited duplications involving Xq26. The first family carries a 5.3 Mb tandem duplication from Xq25q26.2 that includes 26 genes. This duplication was initially identified in a stillborn fetus that presented with microcephaly, IUGR, cleft lip, and additional minor dysmorphic features. Subsequent testing revealed that the mother and two additional children (one male and one female) also carried this duplication. Both of the children were found to present with microcephaly, short stature, poor weight gain, developmental delays, and additional minor dysmorphic features; however, the male child was more severely affected and also presented with IUGR, speech problems, and hypothyroidism. The second family was found to carry a 791 Kb tandem duplication from Xq26.1q26.2 that involves 3 genes (IGSF1, OR13H1, FIRRE) and is contained within the duplication found in the first family. This duplication was identified in a mother and her three sons and was associated with a less severe phenotype that included learning disability and speech delay. Patients with overlapping duplications in this region have been found to share common clinical features that include microcephaly, growth retardation, intellectual/learning disability, and additional dysmorphic features. The breakpoints of the few reported patients vary significantly, making it difficult to define a critical region or to establish a genotype-phenotype correlation. Additional cases are needed to identify the specific triplosensitive genes in the Xq25q26 region. The two additional families that we present provide additional information on the phenotypic spectrum associated with duplications in this region, which can range from stillbirth to minor learning disabilities and speech delay.