Endocrinological Abnormalities Are a Main Feature of 17p13.1 Microduplication Syndrome: A New Case and Literature Review

Abstract

To date, 5 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability was reported as the core feature, together with minor facial dysmorphisms and obesity, but a characteristic phenotype for 17p13.1 microduplication has not been delineated. Here, we describe a patient with a 1.56-Mb de novo duplication in 17p13.1, affected by mild intellectual disability, facial dysmorphisms, obesity, and diabetes. By comparing the different phenotypes of currently described cases, we delineated the main clinical features of 17p13.1 microduplication syndrome. All patients described to date had variable facial dysmorphisms; therefore, it was difficult to define a common facial gestalt. Furthermore, we stress endocrinological abnormalities as important features and the need to monitor these over time.

Keywords: Diabetes; Endocrine disorders; Intellectual disability; Microduplication syndrome 17p13.1; Obesity.

Fig. 1

The patient at 13 years of age. A, B Facial phenotype with a flat occiput, low posterior hairline, rounded face, synophrys, upslanting palpebral fissures, small nose with upturned nostrils, micrognathia, and slightly posteriorly rotated normally shaped ears. C Hands: tapering fingers with hyperconvex, hypoplastic fingernails. D Feet: brachydactyly, hypoplastic toenails. E Coronal FLAIR MRI of the brain shows bilateral hippocampal malrotation (arrows). F Axial FLAIR MRI of the brain shows reduced gyrification of insular cortex on the right posterior side (arrow).

Fig. 2

Results of molecular cytogenetic investigations. A Array-CGH profile of chromosome 17 shows a 1.56-Mb duplicated region in 17p13.1 (chr17: 6,482,088-8,047,770 [h19]). The region harbors 89 RefSeq genes. B, C Results of FISH on interphase nuclei (B) and metaphase chromosomes (C) confirming a tandem 17p13.1 microduplication. TP53 (red) shows 2 signals on the interphase nuclei (arrows). Both signals are localized in chromosome 17p in the metaphase. The green signal shows the centromere region of chromosome 17 as a control (probe D17Z1).

Fig. 3

The UCSC genome browser was utilized to identify the minimal region of overlap for the chromosome 17p duplications (chr17: 7,094,072-7,156,584 [hg19]) identified in the present case and the previous cases reported by Belligni et al. [2012], Coutton et al. [2012], Kuroda et al. [2014], and Mooneyham et al. [2014]. The horizontal black bars show the duplicated regions of patients involved. The red box (bottom) shows the 7 genes located within the minimal region of overlap.