Co‐occurrence of non‐mosaic trisomy 22 and inherited balanced t(4;6)(q33;q23.3) in a liveborn female: Case report and review of the literature

Abstract

Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non-mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non-mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non-mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non-mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed.

Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature

“…Trisomy 22, in its complete or mosaic form, has an estimated incidence of up to 3–5% in spontaneous abortions [ 29 ]. While complete trisomy 22 is often non-compatible with life, leading to death in utero or shortly after birth [ 30 ], mosaic forms may survive through pregnancy and thrive in the postnatal life.…”

Congenital heart defects associated with aneuploidy syndromes: New insights into familiar associations

“…Data is sparse regarding the overall ascertainment of fetal echocardiography leading to a diagnosis of aneuploidy, and there are few or no studies regarding fetuses with aneuploidy assessed by other means, and their subsequent echocardiographic findings (Pavlicek et al, 2019;Tuuli et al, 2009). In addition to the expanded prenatal diagnosis of aneuploidy syndromes with frequent CHDs, postnatal diagnosis of the most severe CHDs in CCHD newborn screening programs has grown rapidly worldwide (Bakker et al, 2019;Liberman et al, 2014;Oster et al, 2016 Smallhorn, & Freedom, 1990Wylie et al, 1994Lin et al, 2007Polli et al, 2014Kosiv, Gossett, Bai, & Collins, 2017Domingo, Carey, Eckhauser, Wilkes, & Menon, 2019Van Praagh et al, 1989Musewe et al, 1990Balderston, Shaffer, Washington, & Sondheimer, 1990Baty et al, 1994Crider, Olney, & Cragan, 2008Savva, Walker, & Morris, 2010Kosiv et al, 2017Abdelgadir, Nowaczyk, & Li, 2013Kehinde et al, 2014Bergstrom et al, 2016Pfitzer et al, 2018;Freeman et al, 2008Lange, Guenther, Busch, Hess, & Schreiber, 2007de Graaf et al, 2015 Prevalence of syndrome per 10,000 livebirths Abbreviations: AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; CHD, congenital heart defect; ETA, elongation of the transverse aorta; HLHS, hypoplastic left heart syndrome; LB, livebirth; PLSVC, persistent left superior vena cava; TAPVC, total anomalous pulmonary venous connection. disability, and high mortality.…”

“…Complete trisomy 22 typically leads to neonatal death (mean survival 4 days of life), with the maximum reported age of 3 years (Heinrich et al, 2012). A review of live-born patients with complete trisomy 22 noted that 92% (24/26) had CHDs (Kehinde et al, 2014). A review of the literature identified septal defects (Kontomanolis, Pandya, & Limperis, 2010;Ma, Ouyang, Hao, Zhao, et al, 2018;McPherson & Stetka, 1990;Naicker & Aldous, 2014), conotruncal anomalies (Stratton et al, 1993;Tinkle, Walker, Blough-Pfau, Saal, & Hopkin, 2003;Xu et al, 2019), aortic arch anomalies (Bacino et al, 1995), hypoplastic right heart (Bacino et al, 1995), and complex CHDs (Bacino et al, 1995;Tonni, Ventura, Pattacini, Bonasoni, & Ferrari, 2012).…”

Syndromes associated with holoprosencephaly

“…Trisomy 22 is a rare condition. Three cases of trisomy 22 and HPE has been reported (Fahmi, Schmerler, & Hutcheon, 1994; Isada, Bolan, Larsen, & Kent, 1990; Kehinde et al, 2014). One case of trisomy 16 has been associated with HPE, Petracchi et al in their study of 13,883 prenatal diagnoses, found 1 case of trisomy 16 presenting with holoprosencephaly.…”