3q26.31–q29 duplication and 9q34.3 microdeletion associated with omphalocele, ventricular septal defect, abnormal first-trimester maternal serum screening and increased nuchal translucency: Prenatal diagnosis and aCGH characterization

New Insights into Kleefstra Syndrome: Report of Two Novel Cases with Previously Unreported Features and Literature Review

“…In particular, double artery umbilical cord, increased nuchal translucency, oligohydramnios, fetus dismaturity in the 3rd trimester, and major malformations can be detected by prenatal US [Stewart et al, 2004;Chen et al, 2013;Hadzsiev et al, 2016;Huang et al, 2017]. In effect, increased nuchal translucency was detected in patient 1.…”

408 kb 15q11.2 microduplication by array comparative genomic hybridization in a fetus presenting with exomphalos, micrognathia, tetralogy ofFallot and normal karyotype: A genetic counseling dilemma in paternal carrier status

“…Very recently Chen et al. () described a prenatal diagnosis and a‐CGH characterization of 3q26.31‐q29 duplication and 9q34.3 microdeletion in a fetus with omphalocele, ventricular septal defect, increased nuchal translucency, abnormal first‐trimester maternal screening and facial dysmorphism. Rare CNVs such as microdeletions or microduplications with a population frequency <1%, are also acquiring importance as susceptibility factors for complex diseases and congenital abnormalities (Greenway et al.…”

“…Tetralogy of Fallot (TOF) has an estimated incidence of 0.28 every 1000 livebirths (Shinebourne and Anderson 2002) and has been demonstrated to be associated to chromosomal abnormalities, such as trisomy 21 (responsible for the 7% of TOF cases) and 22q11.2 microdeletion syndrome (DiGeorge Syndrome, accounting for 10-16% of cases) (Goldmuntz et al 1998;Botto et al 2003). Very recently Chen et al (2013) described a prenatal diagnosis and a-CGH characterization of 3q26.31-q29 duplication and 9q34.3 microdeletion in a fetus with omphalocele, ventricular septal defect, increased nuchal translucency, abnormal first-trimester maternal screening and facial dysmorphism. Rare CNVs such as microdeletions or microduplications with a population frequency <1%, are also acquiring importance as susceptibility factors for complex diseases and congenital abnormalities (Greenway et al 2009;Soemedi et al 2012;Warburton et al 2014).…”

Severe neonatal presentation of Kleefstra syndrome in a patient with hypoplastic left heart syndrome and 9q34.3 microdeletion

“…Additional clinical features often reported in KS include epilepsy, behavioral and psychiatric disorders, brain anomalies, musculoskeletal issues, male genital defects, hearing problems, recurrent infections, and obesity (Willemsen et al, ). Regardless of the molecular mechanism, cardiovascular and renal anomalies have been reported in 40 to 50% and 10 to 15% of patients with KS, respectively (Table ) (Schimmenti et al, ; Ayyash et al, ; Knight et al, ; Dawson et al, ; Cormier‐Daire et al, ; Font‐Montgomery et al, ; Harada et al, ; Iwakoshi et al, ; Stewart et al, ; Kannu et al, ; Kleefstra et al, , 2012; Neas et al, ; Sanger et al, ; Yatsenko et al, ; Tansatit et al, ; Stewart and Kleefstra, ; Nillesen et al, ; Verhoeven et al, ; Willemsen et al, ; Willemsen et al, ; Chen et al, ). The present case is the first report of HLHS in KS, and although renal cystic changes have been documented in a handful of cases, this also represents the first patient with acute kidney failure in the neonatal setting.…”

“…Although morbidity is known to be high in KS, mortality has been less frequently reported. Outside a single case of a 21‐year‐old with a deletion of 9q34 who died of unknown causes, seven cases of infancy/early childhood deaths have been reported (Table ) (Schimmenti et al, ; Ayyash et al, ; Stewart et al, ; Neas et al, ; Yatsenko et al, ; Tansatit et al, ; Chen et al, ). Although all seven cases with reported death had deletions of the critical region, there is no indication that patients with a deletion die at a younger age than patients with a mutation (Willemsen et al, ).…”