Growth failure

Gene: IGF2

Green List (high evidence)

Silver-Russell syndrome-3 (SRS3) is characterized by intrauterine growth retardation with relative macrocephaly, followed by feeding difficulties and postnatal growth restriction. Dysmorphic facial features include triangular face, prominent forehead, and low-set ears. Other variable features include limb defects, genitourinary and cardiovascular anomalies, hearing impairment, and developmental delay. Disruption of any gene in the HMGA2-PLAG1-IGF2 pathway results in a decrease in IGF2 expression and produces an SRS phenotype similar to that of patients carrying 11p15.5 epigenetic defects.

Begemann et al. (2015) performed exome sequencing in 4 affected people with severe growth restriction in one family, and identified a heterozygous nonsense mutation in the IGF2 gene that segregated fully with the disorder. Affected individuals inherited the mutation from their healthy fathers, and it originated from the healthy paternal grandmother. Clinical features occurred only in those who inherited the variant allele through paternal transmission, consistent with maternal imprinting of IGF2.

Many other cases reported since with de novo mutations in IGF2 present on the paternal allele.

Created: 17 Aug 2021, 11:06 p.m. | Last Modified: 17 Aug 2021, 11:06 p.m.

Panel Version: 0.168

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)

Phenotypes
Silver-Russell syndrome 3, OMIM #616489

Publications

• PMID: 26154720, 31544945