Submission Details

Submitter:

Classification:
Definitive
GENCC:100001
Gene:
Disease:
Silver-Russell syndrome 5
Mode Of Inheritance:
Autosomal dominant
Evaluated Date:
06/20/2025
Evidence/Notes:

The HMGA2 (high mobility AT-hook 2) gene located on chromosome 12 at 12q14.3 encodes a encodes a member of the non-histone chromosomal high mobility group (HMG) protein family – architectural factors and essential components of the enhanceosome. Loss of Hmga2 was first reported to be associated with growth restriction in mice (Zhou et al 1995, PMID: 7651535) and microdeletions of 12q had also implicated HMGA2 as a cause of Silver Russell Syndrome (SRS) (OMIM:618908) (Spengler et al., 2010, PMID: 19762329). SRS diagnosis is based on the Netchine-Harbison clinical scoring system (NH-CSS) from Azzi et al. 2015 (PMID: 25951829) Suggestive findings include intrauterine growth restriction, feeding difficulties in early childhood, and postnatal growth failure. Dysmorphic features include triangular face with frontal bossing or prominent forehead, micrognathia, and relative macrocephaly at birth. Skeletal features include fifth finger clinodactyly and/or small hands. Other findings include high pitched voice, developmental delay, and genitourinary abnormalities (Saal et al., 2025, PMID: 20301499).

9 unique variants from 9 individuals in 5 publications including splice (Gorbenko del Blanco et al., 2011, PMID:

PubMed IDs:
7651535 21803798 25809938 34878116 38516887 38840187 40393763
Public Report:
Assertion Criteria:
Submitter Submitted Date:
12/05/2025

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