Chromosome 17q23.1-Q23.2 Duplication Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene duplication syndrome (Chr17:55.46-57.69 Mb).

Clinical Features

Alvarado et al. (2010) identified a recurrent chromosome 17q23.1-q23.2 microduplication in 3 of 66 probands with familial idiopathic clubfoot. Mild short stature was common and 1 female had developmental hip dysplasia. Subtle skeletal abnormalities consisted of broad and shortened metatarsal and calcanei, small distal tibial epiphyses, and thickened ischia. All 7 patients with clubfoot were male, and clubfoot was bilateral in all but 1. The hands and upper extremities were unaffected in all.

Inheritance

Alvarado et al. (2010) found that the chromosome 17q23.1-q23.2 microduplication segregated with autosomal dominant clubfoot in all 3 families but with incomplete penetrance. Of 10 family members with the duplication, 7 had clubfoot, 1 had developmental hip dysplasia, and 2 had a normal physical examination.

Cytogenetics

Alvarado et al. (2010) identified 66 idiopathic clubfoot probands with at least 1 affected first-degree relative and screened 40 probands for genomic copy number variants (CNVs) with Affymetrix Genomewide Human SNP Array 6.0. Nearly identical 2.2-Mb chromosome 17q23.1-q23.2 duplications involving 1,120 markers (55,457,520 to 57,693,617, NCBI36), were identified on copy number analysis performed with the Affymetrix Genotyping Console in 2 unrelated probands. The duplication was not present in 700 controls. Alvarado et al. (2010) also screened DNA from 26 additional probands with familial idiopathic clubfoot for CNVs in this region by using the TaqMan assays and identified the chromosome 17q23.1-q23.2 2.2-Mb duplication in another proband. Alvarado et al. (2010) also identified 2 sibs with clubfoot who had deletion of the same chromosome 17q23.1-q23.2 region (see 613355).