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

Birth Defects Res A Clin Mol Teratol. 2014 Dec;100(12):985-90. doi: 10.1002/bdra.23324. Epub 2014 Nov 7.

Abstract

Background: Kleefstra syndrome arises from haploinsufficiency of EHMT1 caused by either microdeletions at 9q34.3 or intragenic mutations. Patients with Kleefstra syndrome have multisystem involvement including intellectual disability, hypotonia, and characteristic facial features.

Methods: We report on the severe neonatal presentation of the first case of Kleefstra syndrome associated with hypoplastic left heart syndrome and multicystic renal disease in a patient with a 9q34.3 microdeletion.

Results: Array-CGH analysis revealed a 2.1 Mb deletion at 9q34.3, including EHMT1 and NOTCH1.

Conclusion: Kleefstra syndrome is a multisystem disorder with a high frequency of congenital heart disease and less frequently, renal defects. Mortality has rarely been documented, particularly in infancy. Based on the present case and the extant literature, a routine echocardiogram and renal ultrasound should be ordered in all cases of Kleefstra syndrome. The cardiac changes seen in this patient could be the result of the haploinsufficiency of EHMT1, NOTCH1, or their combined effect.

Keywords: 9q34.3 microdeletion; Kleefstra syndrome; chromosomal microarray; hypoplastic left heart syndrome; multicystic renal disease.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromosome Deletion
  • Chromosomes, Human, Pair 9 / genetics*
  • Comparative Genomic Hybridization
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics*
  • Female
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / genetics*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Hypoplastic Left Heart Syndrome / genetics*
  • Infant, Newborn
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Multicystic Dysplastic Kidney / diagnosis
  • Multicystic Dysplastic Kidney / genetics
  • Mutation / genetics
  • Receptor, Notch1 / genetics*
  • Sequence Deletion*
  • Young Adult

Substances

  • NOTCH1 protein, human
  • Receptor, Notch1
  • EHMT1 protein, human
  • Histone-Lysine N-Methyltransferase

Supplementary concepts

  • Kleefstra Syndrome