Duplication of 20p12.3 associated with familial Wolff–Parkinson–White syndrome

Abstract

Wolff-Parkinson-White (WPW) syndrome is caused by preexcitation of the ventricular myocardium via an accessory pathway which increases the risk for paroxysmal supraventricular tachycardia. The condition is often sporadic and of unknown etiology in the majority of cases. Autosomal dominant inheritance and association with congenital heart defects or ventricular hypertrophy were described. Microdeletions of 20p12.3 have been associated with WPW syndrome with either cognitive dysfunction or Alagille syndrome. Here, we describe the association of 20p12.3 duplication with WPW syndrome in a patient who presented with non-immune hydrops. Her paternal uncle carries the duplication and has attention-deficit hyperactivity disorder and electrocardiographic findings consistent with WPW. The 769 kb duplication was detected by the Affymetrix Whole Genome-Human SNP Array 6.0 and encompasses two genes and the first two exons of a third gene. We discuss the potential role of the genes in the duplicated region in the pathogenesis of WPW and possible neurobehavioral abnormalities. Our data provide additional support for a significant role of 20p12.3 chromosomal rearrangements in the etiology of WPW syndrome.

Utility of chromosomal microarray for diagnosis in cases of nonimmune hydrops fetalis

“…A substantial proportion of NIHF cases also remain of unknown etiology despite evaluation with karyotype and CMA. There are very few case reports of copy number variants (CNVs) detected by CMA in the literature for NIHF cases, and many of the reported CNVs could have been detected by karyotype. Examples of CNVs reported with NIHF that would only be detected by CMA include 22q11.2 microdeletion or microduplication syndromes, 16p13.3 microdeletion with alpha thalassemia, 11p15.4 microdeletion with εγδβ‐thalassemia, 20p12.3 microduplication with Wolff‐Parkinson‐White syndrome, 1p12p21 microdeletion with congenital diaphragmatic hernia, and 3q29 microduplication and 15q24.3 microdeletion with cardiac dysfunction …”

“…8 A substantial proportion of NIHF cases also remain of unknown etiology despite evaluation with karyotype and CMA. 9 There are very few case reports of copy number variants (CNVs) detected by CMA in the literature for NIHF cases, [10][11][12][13] of CNVs reported with NIHF that would only be detected by CMA include 22q11.2 microdeletion or microduplication syndromes, 14,15 16p13.3 microdeletion with alpha thalassemia, 16 11p15.4 microdeletion with εγδβ-thalassemia, 17 20p12.3 microduplication with Wolff-Parkinson-White syndrome, 12 1p12p21 microdeletion with congenital diaphragmatic hernia, 11 and 3q29 microduplication and 15q24.3 microdeletion with cardiac dysfunction. 18 We designed a retrospective cohort study of all NIHF cases undergoing CMA at our institution over the past 10 years, in order to determine the utility of CMA for establishing a diagnosis in cases of isolated NIHF as well as NIHF with concurrent structural anomalies.…”

Combined immunodeficiency in a 3‐year‐old boy with 16p11.2 and 20p12.2‐11.2 chromosomal duplications

“…Most of the gains involve most of the 20p arm from 20p11.2 to 20p terminus. Only three cases had smaller duplications involving from <1 to 3 cytobands with the smallest being of 700 kb that was recently associated with Wolff–Parkinson–White syndrome [Mills et al, ]. The latter did not have trisomy 20p syndrome.…”

“…Schematic representation of genetic mapping of all reported cases with 20p pure duplication (PD) and with a duplication and a deletion (dup/del) [Moog et al, ; Oppenheimer et al, ; Sidwell et al, ; de Ravel et al, ; Ardalan et al, ; Chaabouni et al, ; Leclercq et al, ; D'Angelo et al, ; Mills et al, ]. The features reported in most of them: Developmental delay (DD), prominent cheek (PC), palpebral fissures (>: equals upward slant, <: equals downward slant), speech delay (SD), and cranial anomalies (CA) (+: present; –: negative) are also found in our patient.…”

Brief history of arrhythmia in the WPW syndrome – the contribution of George Ralph Mines

“…The first article using the term ‘Kent bundle’ was that of Wolferth and Wood in 1933 (Wolferth & Wood, 1933). Subsequently, many papers, and even recent textbooks, continued the use of ‘Kent bundle’ (Hu et al 2011; Aanhaanen et al 2011 a ; Mills et al 2013). Moreover, to date, lay sources found on the internet (http://www.uptodate.com; http://www.wikipedia.org) describe accessory connections that are present in WPW patients as ‘bundles of Kent’.…”