Congenital Heart Defect

Gene: RERE

Green List (high evidence)

Niehaus, Kim & Manning (2022) (PMID: 36053530) provide an updated literature review, and assert 23 cases have been reported of Neurodevelopmental Disorders with or without Anomalies of the Brain, Eye, or Heart (NEDBEH) caused by heterozygous pathogenic variants in RERE. Eleven of the 23 patients reported (48%) had congenital heart disease, most commonly septal disease. All variants were de novo except one, inherited from a mother with mild symptoms. Variant types include missense, frameshift, small deletions & duplications and 1 large deletion. Missense variants in the atrophin-1 domain seem to present with a more severe phenotype than loss-of-function variants

NEDBEH is fully penetrant but has variable expressivity – congenital heart anomalies not always present.

ClinGen: definitive association with AD complex neurodevelopmental disorder with or without congenital anomalies.
Sources: Literature, ClinGen

Created: 2 Nov 2023, 2:47 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (OMIM #616975)

Publications

• 29330883, 27087320, 33772547, 36053530