FOXC1 haploinsufficiency due to 6p25 deletion in a patient with rapidly progressing aortic valve disease

Abstract

6p25 deletion is a rare but well-known entity. The main clinical features include an abnormal facial appearance, developmental delay, and ocular anomalies. Cardiac anomalies are frequently seen but remain poorly delineated. We describe a 4-year-old girl with 6p25.3 deletion, which includes the FOXC1 gene, typical dysmorphic features associated with developmental delay and oculo-motor anomalies. Aortic valve dysplasia was diagnosed early in life. The cardiac lesion progressed very rapidly between the age of 3 and 4 years requiring aortic valve replacement. Genomic analysis of blood and excised valve tissue showed down-regulation of FOXC1 but also FOXC2 expression in the diseased aortic valve. This allows us to speculate on the potential role of FOXC1 in aortic valve anomalies.

The Oculome Panel Test

“…In addition, the affected children themselves may benefit by timely referral for those with FOXC1 mutations to other specialists to screen and monitor for associated life-threatening cardiovascular defects. 66,67 There is also a growing body of evidence indicating that the severity of early-onset glaucoma differs between different genetic causes. 25 Case 74 was referred with an anterior segment dysgenesis phenotype of congenital corneal opacity, iridocorneal adhesions and scleralization of the peripheral cornea.…”

Bioinformatic identification of hub genes and related transcription factors in low shear stress treated endothelial cells

“…Human patients with FOXC1 mutations were associated with congenital heart disease [39]. In mice, knock-out of FOXC1 in ECs impaired valve maturation [40]. There were experiments which demonstrated that shear stimulation of FOXC1 regulated cytoskeletal activity [41].…”

Detection of submicroscopic chromosomal aberrations by chromosomal microarray analysis for the prenatal diagnosis of central nervous system abnormalities

“…A previous study showed that the 6p25.3 deletion is a rare, but well‐known entity. The major clinical manifestations include developmental delay, a special facial appearance, congenital heart disease, and CNS abnormalities 13‐15 . Aldinger et al 16 reported that the FOXC1 gene is necessary for normal cerebellar development and is a main contributor to Dandy‐Walker malformation.…”