Monozygotic Twins with 17q21.31 Microdeletion Syndrome

Abstract

Chromosome 17q21.31 microdeletion syndrome is a genomic disorder caused by a recurrent 600 kb long deletion. The deletion affects the region of a common inversion present in about 20% of Europeans. The inversion is associated with the H2 haplotype carrying additional low-copy repeats susceptible to non-allelic homologous recombination, and this haplotype is prone to deletion. No instances of 17q21.31 deletions inherited from an affected parent have been reported, and the deletions always affected a parental chromosome with the H2 haplotype. The syndrome is characterized clinically by intellectual disability, hypotonia, friendly behavior and specific facial dysmorphism with long face, large tubular or pear-shaped nose and bulbous nasal tip. We present monozygotic twin sisters showing the typical clinical picture of the syndrome. The phenotype of the sisters was very similar, with a slightly more severe presentation in Twin B. The 17q21.31 microdeletion was confirmed in both patients but in neither of their parents. Potential copy number differences between the genomes of the twins were subsequently searched using high-resolution single nucleotide polymorphism (SNP) and comparative genome hybridisation (CGH) arrays. However, these analyses identified no additional aberrations or genomic differences that could potentially be responsible for the subtle phenotypic differences. These could possibly be related to the more severe perinatal history of Twin B, or to the variable expressivity of the disorder. In accord with the expectations, one of the parents (the mother) was shown to carry the H2 haplotype, and the maternal allele of chromosome 17q21.31 was missing in the twins.

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

“…A search of the medical literature identified 23 articles describing the clinical features of 81 patients with KdVS. [1][2][3][4][5]13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

“…The facial features are similar between the 17q21.31 deletion group (Figure 2) and the KANSL1 SNV group (Figure 3 Other nonfacial dysmorphic features that have been reported in the medical literature include fetal finger pads, 22 slender lower limbs, 13 and postaxial polydactyly of fingers and toes. 24,32 Musculoskeletal anomalies Musculoskeletal anomalies were present in 77% of our cases and included tracheo/laryngomalacia, pectus excavatum or carinatum, scoliosis/kyphosis, hip dislocation/dysplasia, joint hypermobility, and positional deformities of the feet. Tracheo/laryngomalacia (21%) can occasionally result in severe respiratory problems (case 38 needed supraglottoplasty twice).…”

“…13,18,22 Ectodermal abnormalities Ectodermal abnormalities were present in 67% of our cases and have previously been described. 13,18,22,24,26,30 Skin involvement included, among others, multiple nevi, depigmentosa, hyperkeratosis, eczema, keratosis pilaris, café-au-lait maculae, ichthyosis vulgaris, acne vulgaris, piezogenic papules, and hemangiomas. Importantly, case 17 developed melanoma at 9 years of age.…”

“…24 Case 25 had vitiligo and developed Addison's disease with GAD65 autoantibodies. This case has been described in more detail by Maley et al 31 Other clinical features that might be of importance are hypertension (case 20), neutropenia (cases 7 and 25), and recurrent infections in at least 11 out of 45 cases (24%).…”

Central and Eastern European Special Issue

“…Finally, Oniszczenko and Dragan's (2014) review of twin research in Poland is followed by an original article by Toth et al (2014), assessing the genetic covariance between central corneal thickness and anterior chamber volume. The special issue is concluded by Vlckova et al's (2014) gene expression study highlighting that the most modern forms of twin research are present in the region and conducted to the highest standards.…”