Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disordersGene: NFIB
Macrocephaly is a consistent feature, generalised overgrowth is not. Out of the 8 patients originally reported, only one has height/weight >99th centile.
Created: 4 Jul 2020, 3:21 a.m. | Last Modified: 4 Jul 2020, 3:21 a.m.
Panel Version: 1.94
NFIB is associated with a phenotype in OMIM and probably associated with a phenotype in Gene2Phenotype.
Expert review from Konstantinos Varvagiannis: "Schanze et al. (PMID: 30388402) report on the phenotype related to NFIB haploinsufficiency. 10 individuals with intragenic NFIB or larger deletions encompassing also other genes as well as 8 individuals with nucleotide variants (5 loss-of-function and 3 missense ones) are described. Intellectual disability was a universal feature while macrocephaly was noted in the majority of the patients. The phenotype of individuals deletions was similar to the phenotype of intragenic mutations as also seems to be the case with the degree of ID. Functional studies support loss of function for the pathogenic missense variants reported. Cortical-specific knockout of Nfib in mice results in enlargement of the cortex." -- copied from "Intellectual disability" panel (code: 285).
After discussion with the clinical team, it was decided that NFIB is relevant for the " Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders" panel and there is enough evidence to support a gene-disease association. Therefore, NFIB has been given a green gene rating.
Sources: Expert list
Created: 18 Mar 2019, 11:57 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Macrocephaly, acquired, with impaired intellectual development, 618286
Gene: nfib has been classified as Green List (High Evidence).
gene: NFIB was added gene: NFIB was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders. Sources: Expert list Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NFIB were set to 30388402 Phenotypes for gene: NFIB were set to Macrocephaly, acquired, with impaired intellectual development, 618286 Review for gene: NFIB was set to GREEN