Fetal anomalies
Gene: GRHL2

GRHL2 (grainyhead like transcription factor 2)
EnsemblGeneIds (GRCh38): ENSG00000083307
EnsemblGeneIds (GRCh37): ENSG00000083307
OMIM: 608576, Gene2Phenotype
GRHL2 is in 6 panels

3 reviews

Natalie Chandler (North Thames GLH)

I don't know

Previous review amber based on biallelic variants- no new evidence so suggest to keep amber for biallalic. PMID41172132 monoallelic LOF variants lead to orofacial cleft 4 de novo, 1 paternal missense. LOF variants prev reported with hearing loss (no reports of cleft but not the focus of papers). Would not qualify for R21 testing with isolated cleft. ? spectrum hom LOF lethal, missense server, mono LOF milder? Suggest keep amber but change to monoallelic and biallelic?
Created: 29 Oct 2026, 3:51 p.m. | Last Modified: 29 Oct 2026, 3:51 p.m.

Panel Version: 8.25

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Ectodermal dysplasia/short stature syndrome, OMIM:616029; cleft palate, MONDO:0016064

Publications

Created: 29 Oct 2026, 3:51 p.m.
Last Modified: 29 Oct 2026, 3:51 p.m.
Panel version: 8.25

Ida Ertmanska (Genomics England Curator)

I don't know

This gene and phenotype were reviewed during meetings in July and August 2026. The meetings included representatives of the North Thames and Central and South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Louise Carr (North Thames GLH), Sarah Graham & Elizabeth Young (Central & South GLH), and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Sunayna Best, Soo-Mi Park & Tessa Homfray (R21 Clinical Oversight Group).
Created: 29 Oct 2026, 4:13 p.m. | Last Modified: 29 Oct 2026, 4:13 p.m.

Panel Version: 8.26

BIALLELIC CASES:
PMID: 25152456 Petros et al., 2013
2 consanguineous Kuwaiti families with 6 total affected individuals with ectodermal dysplasia. Shared features: nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, short stature (≤25th percentile), and dysphagia. Patients in family ED-01 also presented with sensorineural deafness. ED-01 members were homozygous for GRHL2 c.1192T>C (p.Tyr398His), and ED-02 were homozygous for c.1445T>A (p.Ile482Lys).

PMID: 27612988 Walne et al., 2016
Report of 2 consanguineous families from Kuwait and Turkey.
Family 9: index patient homozygous for GRHL2 c.1445T>A p.Ile482Lys
Family 10: index patient homozygous for GRHL2 c.1213C>A p.Pro405Thr
Shared phenotype of the 2 probands: abnormal dentition, nail dystrophy, abnormal skin pigmentation, growth restriction (short stature). No mention of hearing loss.
Created: 22 May 2026, 10:42 a.m. | Last Modified: 22 May 2026, 10:42 a.m.

Panel Version: 7.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ectodermal dysplasia/short stature syndrome, OMIM:616029

Publications

Created: 22 May 2026, 10:42 a.m.
Last Modified: 22 May 2026, 10:42 a.m.
Panel version: 8.26

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for ECTODERMAL DYSPLASIA/SHORT STATURE SYNDROME
Created: 11 Dec 2018, 9:05 a.m.

In the original PAGE file, MOP listed as All missense/in frame.
Created: 8 Nov 2018, 4:45 p.m.

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.9

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

NHS GMS
Expert Review Amber
PAGE DD-Gene2Phenotype

Phenotypes

Ectodermal dysplasia/short stature syndrome, OMIM:616029
cleft palate, MONDO:0016064

OMIM

608576

Clinvar variants

Variants in GRHL2

Penetrance

None

Publications

Panels with this gene