Chromosome 5q34-q35.2 microdeletion and congenital heart disease

An adult female with chromosome 5q34-q35.2 microdeletion: A rare syndromic presentation of left ventricular non-compaction and congenital heart disease

Chromosome 5

Microdeletions in the distal segment of chromosome 5q have rarely been reported in the literature with less than 20 published cases. Common features that have been identified in distal 5q deletions included failure to thrive, microcephaly, developmental delay/intellectual disability, abnormal craniofacial phenotypes, and cardiac anomalies.

The proposed smallest region of overlap (SRO) is estimated to be approximately 2.2 Mb and contains 19 genes, including the NKX2-5 gene. The NKX2-5 gene is considered to be crucial for cardiac and conduction system development.

In this article, the authors report on a 24-year-old female, the first adult described with an interstitial 5q34-q35.2 deletion. Clinical findings included congenital heart defects, microcephaly, minor facial dysmorphism, developmental delay across all domains, and a diagnosis of autism spectrum disorder since the age 18. The congenital heart defects included left ventricular non-compaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM).

The authors state the congenital heart defects seen in the patient, and other patients with distal 5q deletions, are most likely caused by haploinsufficiency of NKX2-5. This lends plausibility to the association between distal 5q deletions and cardiomyopathies. Additionally, the authors speculate that the haploinsufficiency of two other genes in the deleted areas GABRB2 and KCNIP1 could contribute to the intellectual disability, developmental delay, and behavioral abnormalities seen in this patient and others with distal 5q deletions.

Arya P. et al. “An Adult Female with 5q34-q35.2 Deletion: A Rare Syndromic Presentation of Left Ventricular Non-Compaction and Congenital Heart Disease.” European Journal of Medical Genetics, 2019, [ahead of print] doi:10.1016/j.ejmg.2019.103797

Articles of the month are chosen from newly published genetic research by CDO consulting medical advisor and geneticist, Dr. Iosif Lurie, M.D. PhD  For more information on any article please contact info@chromodisorder.org