Aortopathy in the 7q11.23 microduplication syndrome

Abstract

The 7q11.23 microduplication syndrome, caused by the reciprocal duplication of the WilliamsBeuren syndrome (WBS) deletion region, is a genomic disorder with an emerging clinical phenotype. Dysmorphic features, congenital anomalies, hypotonia, developmental delay highlighted by variable speech delay, and autistic features are characteristic findings. Congenital heart defects, most commonly patent ductus arteriosus, have been reported in a minority of cases.Included in the duplicated region is elastin (ELN), implicated as the cause of supravalvar aortic stenosis in WBS. Here we present a series of eight pediatric patients and one adult with 7q11.23 microduplication syndrome, all of whom have aortic dilation, the opposite vascular phenotype of the typical supravalvar aortic stenosis found in WBS. The ascending aorta was most commonly involved, while dilation was less frequently identified at the aortic root and sinotubular junction.The findings in these patients support a recommendation for cardiovascular surveillance in patients with 7q11.23 microduplication syndrome.

Children with 7q11.23 duplication syndrome: Psychological characteristics

“…Subsequent FISH testing indicated that this child’s duplication corresponded to the classic WS deletion region (hereafter, classic Dup7). In the ensuing nine years, 30 children with classic Dup7 aged 6 months to 17 years have been described as part of case series [5 in Berg et al, 2007; 14 in van der Aa et al, 2009; 5 in Dixit et al, 2013; 6 in Parrott et al, 2015] and mean performance levels on various psychological assessments were reported by Sanders et al [2011] for four children with classic Dup7. In addition, 12 children with classic Dup7 were described in individual case reports [Somerville et al, 2005; Kriek et al, 2006; Depienne et al, 2007, 2009; Torniero et al, 2007; Merritt and Lindor, 2008; Orellana et al, 2008; Torniero et al, 2008; Malenfant et al, 2012; Değerliyurt et al, 2012; McGrew et al, 2012; Prontera et al, 2014; Zarate et al, 2014].…”

“…Thirteen adults with classic Dup7 also were included in case series or individual case reports. Two individuals (aged 19 and 23 years) were probands [Berg et al, 2007; Kirchhoff et al, 2007]; the remaining 11 had one or more children with classic Dup7 and were identified primarily by cascade testing [2 in Berg et al, 2007; 1 in Merritt and Lindor, 2008; 1 in Torniero et al, 2008; 6 in van der Aa et al, 2009; 1 in Parrott et al, 2015]. Several additional individuals with larger or smaller duplications of 7q11.23 have been included in some of the case series.…”

Aortic dilation, genetic testing, and associated diagnoses

“…In this population some of the diagnoses included major aneuploidies that should be easily [6][7][8][18][19][20][21][22][23][24][25] In many cases, in spite of lacking further supporting clinical evidence of a direct link between AoD and the genes involved in the remaining patients with cytogenetic abnormalities, other potential candidate genes with relationships to cardiac morphogenesis or pathology were identified ( Table 3). [26][27][28][29][30][31][32][33][34][35] We also were able to identify other less common genetic conditions in this population.…”

Monogenic and chromosomal causes of isolated speech and language impairment

“…Most duplication carrier parents showed a history of learning difficulties and/or language delay but were employed and functioning well in adult life 23 24. Due to the finding of cardiac defects and aortopathy in a subset of individuals, cardiovascular surveillance has been recommended for these patients 26. Minor dysmorphic features, neonatal hypotonia, various brain anomalies, cleft palate, epilepsy, cryptorchidism, joint laxity, attention-deficit hyperactivity disorder (ADHD) and autistic features have also been reported in some individuals 23 27.…”