Congenital heart defects in NIPBL

Congenital heart defects in NIPBL are frequent with Polish CdLS patients


Mutations in NIPBL are detected in approximately 47-60% of Cornelia de Lange Syndrome (CdLS1, OMIM 122470) patients. In 20-35% patients positive for variants affecting NIPBL, congenital heart defects (CHD) are observed. 1 2 3 4 5

Materials and methods

63 patients with confirmed diagnosis of CdLS and NIPBL mutations /rearrangements were enrolled in the study. In all individuals extensive cardiologic examination was conducted.


Apart from small heart defects, which resolved spontaneously during the first 2 years of life, CHDs were diagnosed in 20/63 patients (32%). The most common CHDs observed were: isolated valvular pulmonary stenosis (n=4, 6%), tetralogy of Fallot (ToF) (n=3, 5%), isolated ventricular septal defect (VSD) (n=3, 5%) and mitral insufficiency (n=3, 5%). In addition, other defects such as atrial septal defect, atrioventricular canal (AVC), aortic valve defects, and hypoplastic left heart syndrome were observed in single individuals. In eight patients (13%) significant heart defects, such as ToF, AVC, VSD, required surgery in the first year of life. One of the patients (n=1, 2%), with a most complex defect, was considered unable to have treatment and subsequently died in the neonatal period. The other 12 patients (n=12, 19%) did not require any treatment and are still under cardiologic surveillance.

Conclusions: The incidence of CHDs in a group of patients with mutations in NIPBL (32%) is significantly higher than in the general population (1%). Therefore, we recommend detailed cardiac evaluation at diagnosis for patients diagnosed with CdLS.

  1. ^ Ayerza Casas A, Puisac Uriol B, Teresa Rodrigo ME, Hernández Marcos M, Ramos Fuentes FJ, Pie Juste J. Cornelia de Lange syndrome: Congenital heart disease in 149 patients. Med Clin (Barc) 2017;149:300–2.
  2. ^ Chatfield KC, Schrier SA, Li J, Clark D, Kaur M, Kline AD, et al. Congenital heart disease in Cornelia de Lange syndrome: phenotype and genotype analysis. Am J Med Genet A 2012;158A:2499–505.
  3. ^ Kline AD, Moss JF, Selicorni A, Bisgaard A-M, Deardorff MA, Gillett PM, et al. Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement. Nat Rev Genet 2018;19:649–66.
  4. ^
    1. Mehta AV, Ambalavanan SK. Occurrence of congenital heart disease in children withBrachmann-de Lange syndrome. Am J Med Genet 1997;71:434–5.
  5. ^ Selicorni A, Colli AM, Passarini A, Milani D, Cereda A, Cerutti M, et al. Analysis of congenital heart defects in 87 consecutive patients with Brachmann-de Lange syndrome. Am J Med Genet A 2009;149A:1268–72

Presenting Author: Jolanta Wierzba

Authors: Piotr Potaz 1, Jolanta Wierzba 2, Natalia Krawczyńska 3,4,  Karolina Sledzińska 2, Bartosz Wasag 3,4 , Frank J. Kaiser 5 , Ilaria Parenti 5, Joanna Kwiatkowska 1

Keywords: Cornelia de Lange syndrome, NIPBL, congenital heart defects (CHD)

1) Department of Pediatric Cardiology and Congenital Heart Malformations, Medical University of Gdansk, Poland
2) Department of General Nursing, Medical University of G 3 Department of Biology and Medical Genetics, Medical University of Gdansk, Poland
3) Department of Biology and Medical Genetics, Medical University of Gdansk, Poland
4) Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Poland.
5) Section for Functional Genetics at the Institute of Human Genetics, Universität zu Lübeck, Lübeck, Germany

Page history
Last modified by Gerritjan Koekkoek on 2023/03/29 17:08
Created by Gerritjan Koekkoek on 2019/07/09 16:27



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