Hypoplastic left heart syndrome and 21q22.3 deletion

Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect (CHD), associated with extracardiac anomalies in the 15–28% of cases, in the setting of chromosomal anomalies, mendelian disorders, and organ defects. We report on a syndromic female newborn with HLHS and terminal 21q22.3 deletion (del 21q22.3), investigated by Fluorescence In Situ Hybridization (FISH) using a panel of 26 contiguous BAC probes. Although rare, del 21q22.3 has been described in two additional patients with HLHS. In order to investigate the frequency and role of this chromosomal imbalance in the pathogenesis of left‐sided obstructive heart defects, we screened for del 21q22.3 a series of syndromic and non‐syndromic children with HLHS, aortic coarctation and valvular aortic stenosis, consecutively admitted to our hospital in a three‐year period. Although none of the 56 analyzed patients were hemizygous for this region, the present case report and published patients argue that del 21q22 should be added to the list of chromosomal imbalances associated with HLHS. Accordingly, the presence of a cardiac locus mapping in the critical region cannot be excluded. © 2015 Wiley Periodicals, Inc.

[1]  A. Malashicheva,et al.  Variants in the NOTCH1 gene in patients with aortic coarctation. , 2014, Congenital heart disease.

[2]  Ankita Patel,et al.  MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development. , 2013, Human molecular genetics.

[3]  Murim Choi,et al.  De novo mutations in histone modifying genes in congenital heart disease , 2013, Nature.

[4]  F. Alkuraya,et al.  Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome. , 2013, American journal of human genetics.

[5]  S. Gilboa,et al.  Patterns in the prevalence of congenital heart defects, metropolitan Atlanta, 1978 to 2005. , 2013, Birth defects research. Part A, Clinical and molecular teratology.

[6]  R. Axt‐Fliedner,et al.  Fetal diagnosis of hypoplastic left heart, associations and outcomes in the current era. , 2012, Ultraschall in der Medizin.

[7]  L. Galletti,et al.  Identification of de novo mutations and rare variants in hypoplastic left heart syndrome , 2012, Clinical genetics.

[8]  M. Digilio,et al.  Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. , 2012, American journal of human genetics.

[9]  A. Marelli,et al.  Hypoplastic Left Heart , 2012 .

[10]  M. Digilio,et al.  Hypoplastic Left Heart Syndrome in Patients With Kabuki Syndrome , 2010, Pediatric Cardiology.

[11]  Emily H Turner,et al.  Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome , 2010, Nature Genetics.

[12]  Joseph T. Glessner,et al.  Common Variation in ISL1 Confers Genetic Susceptibility for Human Congenital Heart Disease , 2010, PloS one.

[13]  J. Allanson,et al.  Management of Genetic Syndromes: Cassidy/Management , 2010 .

[14]  A. Geddis,et al.  Deletion of JAM‐C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice , 2009, American journal of medical genetics. Part A.

[15]  B. Dallapiccola,et al.  Autosomal dominant inheritance of aplasia cutis congenita and congenital heart defect: A possible link to the Adams–Oliver syndrome , 2008, American Journal of Medical Genetics. Part A.

[16]  Lisa J. Martin,et al.  Hypoplastic left heart syndrome is heritable. , 2007, Journal of the American College of Cardiology.

[17]  V. García-Patos,et al.  Aplasia cutis associated with coarctation of the aorta: could this be an incomplete form of Adams–Oliver syndrome? , 2007, The British journal of dermatology.

[18]  D. Srivastava,et al.  Mutations in NOTCH1 cause aortic valve disease , 2005, Nature.

[19]  J. Roos‐Hesselink,et al.  Autosomal dominant inheritance of left ventricular outflow tract obstruction , 2005, American journal of medical genetics. Part A.

[20]  S. Leal,et al.  Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability , 2005, American journal of medical genetics. Part A.

[21]  V. Ho,et al.  Association Between Fetal Lymphedema and Congenital Cardiovascular Defects in Turner Syndrome , 2005, Pediatrics.

[22]  P. Lichter,et al.  In Situ Hybridization to Metaphase Chromosomes and Interphase Nuclei , 1997, Current protocols in human genetics.

[23]  K. Jones,et al.  The 11q terminal deletion disorder: A prospective study of 110 cases , 2004, American journal of medical genetics. Part A.

[24]  A. Chokkalingam,et al.  Prevalence of congenital cardiovascular malformations among relatives of infants with hypoplastic left heart, coarctation of the aorta, and d‐transposition of the great arteries , 2004, American journal of medical genetics. Part A.

[25]  J. Belmont,et al.  Identification and Functional Analysis of ZIC3 Mutations in Heterotaxy and Related Congenital Heart Defects , 2022 .

[26]  E. Goldmuntz,et al.  NKX2.5mutations in patients with congenital heart disease , 2003 .

[27]  D. Elliott,et al.  Cardiac homeobox gene NKX2-5 mutations and congenital heart disease: associations with atrial septal defect and hypoplastic left heart syndrome. , 2003, Journal of the American College of Cardiology.

[28]  P. Pradat,et al.  The Epidemiology of Cardiovascular Defects, Part I: A Study Based on Data from Three Large Registries of Congenital Malformations , 2003, Pediatric Cardiology.

[29]  David I. Wilson,et al.  Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis. , 2002, Genomics.

[30]  M. Porteous.  Management of genetic syndromes , 2002, Human Genetics.

[31]  D. Warburton,et al.  Hypoplastic left heart in a female infant with partial trisomy 4q due to de novo 4;21 translocation. , 2002, American journal of medical genetics.

[32]  L. Bailey,et al.  Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE). , 2001, Mutation research.

[33]  E. Zackai,et al.  Down syndrome congenital heart disease: A narrowed region and a candidate gene , 2001, Genetics in Medicine.

[34]  L. Mazzanti,et al.  Congenital heart disease in patients with Turner’s syndrome , 1998 .

[35]  L. Holmes,et al.  Adams-Oliver syndrome associated with cardiovascular malformations. , 1998, Clinical dysmorphology.

[36]  R. Abdulla.  Perspective in Pediatric Cardiology. Volume 5. Genetic and Environmental Risk Factors of Major Cardiovascular Malformations , 1998, Pediatric Cardiology.

[37]  C. Cole,et al.  Physical findings in 21q22 deletion suggest critical region for 21q- phenotype in q22. , 1995, American journal of medical genetics.

[38]  B. Dallapiccola,et al.  Coarctation of the aorta, interrupted aortic arch, and hypoplastic left heart syndrome in three generations. , 1993, Journal of medical genetics.

[39]  T Mori,et al.  [Turner syndrome]. , 1993, Ryoikibetsu shokogun shirizu.

[40]  K. Berg,et al.  Cardiovascular Diseases: Genetics, Epidemiology and Prevention , 1991 .

[41]  E. Zackai,et al.  Genetic disorders and major extracardiac anomalies associated with the hypoplastic left heart syndrome. , 1988, Pediatrics.

[42]  M. Šamánek,et al.  Distribution of age at death in children with congenital heart disease who died before the age of 15. , 1988, British heart journal.

[43]  D. Behrendt.  Hypoplastic left heart. , 1982, The Annals of thoracic surgery.

[44]  Shokeir Mh.  Hypoplastic left heart. Evidence for possible autosomal recessive inheritance. , 1974 .

[45]  M. Shokeir.  Hypoplastic left heart. Evidence for possible autosomal recessive inheritance. , 1974, Birth defects original article series.

[46]  G. Burch.  [Cardiovascular diseases]. , 1956, Revista medica cubana.