Congenital Heart Defect

Gene: MAP3K7

Green List (high evidence)

CSCF - primarily caused by loss of function variants.
FMD2 - primarily caused by gain of function variants.

PMID: 27426734 - Monoallelic missense and in-frame deletion variants were identified in the MAP3K7 gene in six individuals affected with CSCF from four unrelated families. All met the clinical feature criteria of CSCF, including skeletal and facial features, and cardiac defects (including VSD (1/6), ASD (1/6) and valve dysplasia (6/6)). One family with 3 affected individuals across 2 generations was reported.

PMID: 29467388 - One case with a splice variant creating a new splice acceptor site causing an in-frame insertion of 2 amino acids. A heart ultrasound at birth revealed patent foramen ovale with left-right shunt and two small muscular ventricular septal defects, mitral and tricuspid valves dysplasia and mild, non-progressive aortic arch hypoplasia.

PMID: 35730652 - 14 novel patients with CSCF + 2 with FMD2. 9/15 with Congenital Heart Defects (including the 2 cases with FMD2), 2/12 Ventricular septal defects, 1/13 Atrial septal defects, 4/14 Cardiomyopathy. CSCF cases include one family with 2 individuals across 2 generations.
Sources: Other

Created: 20 Nov 2023, 1:53 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiospondylocarpofacial syndrome (CSCF) MIM# 157800; Frontometaphyseal dysplasia 2 (FMD2) MIM# 617137

Publications

• PMID: 27426734
• 29467388
• 35730652
• 27426733