Congenital Heart Defect

Gene: FOXP1

I don't know

Limited evidence, Amber rating in view of supportive mouse model.

Created: 26 Jul 2022, 4:01 a.m. | Last Modified: 26 Jul 2022, 4:01 a.m.

Panel Version: 0.239

Phenotypes
Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670

I don't know

Best evidence of association with CHD comes from PMID:29090079 but only for two patients and one with very mild CHD only. Study is a prospective investigation of nine children with FOXP1 syndrome using a battery of standardized clinical assessments, two had CHD (one with pulmonary stenosis, the other with self-resolving PDA). Authors recommend cardiac screening for patients with FOXP1 neurodevelopmental syndrome.

PMID:23766104: Single patient with CHD (AVSD, hypoplastic left ventricle and aortic arch, left atrioventricular valve stenosis, bilateral superior vena cavae, transposed great vessels) and cryptorchidism and a novel 3p14 microdeletion involving first 4 exons of FOXP1, inherited from an unaffected mother. FOXP1 sequenced in 82 patients with AVSD or HLHS: 2/82 patients had FOXP1 variant c.1702C>T;p.(Pro568Ser), inheritance unknown, variant present gnomAD in 153 hets, benign/likely benign in ClinVar .

PMID: 25908055; 22290856: CHD associated with 3p14 contiguous gene deletion syndrome involving FOXP1 and up to 30 other genes.

Homozygous null mice have CHD (MGI ID:1914004; PMID: 15342473).
Sources: Literature, Expert list

Created: 23 Jul 2022, 1:42 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome

Publications

• 29090079
• 23766104

Variants in this GENE are reported as part of current diagnostic practice