Response to the Letter to the Editor: Sitte-Zöllner A, Walcher F, Geginat G, Piatek S. Z Orthop Unfall 2017; 155: 344 – 345. doi:10.1055/s-0043-103015

In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease

“…[9] Cytogenetic analysis and genomic arrays have helped to understand subchromosomal structural rearrangements, highlighting frequent 3-Mb deletions at 22q11.2 in DiGeorge (velocardiofacial) syndrome. [10][11][12][13] Deletions are present in approximately 2% of all cases of CHD and in 13% of individuals with specific cardiac malformations, as determined by fluorescence in situ hybridization [14,15] and targeted amplification. [16] About 25% of sporadic CHD cases are caused by the coexistence of karyotype or microarray-detected abnormalities.…”

“…Furthermore, patients with critical and complex malformations display the greatest frequency of de novo damaging variants in genes linked to CHD, which provides convincing evidence of severe adverse effects on reproductive health; and the evolutionary restriction on numerous genes connected with CHD. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The question of why CHD is the most prevalent congenital abnormality is intriguing. One hypothesis suggests that the intricate developmental processes involved in heart formation are highly responsive to alterations in gene dosage for many essential genes and pathways.…”