Congenital fibrosis of the extraocular muscles
Gene: ZFHX4EnsemblGeneIds (GRCh38): ENSG00000091656
EnsemblGeneIds (GRCh37): ENSG00000091656
OMIM: 606940, Gene2Phenotype
ZFHX4 is in 3 panels
2 reviews
Ida Ertmanska (Genomics England Curator)
Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous ZFHX4 variants and isolated congenital ptosis. Hence, this gene can be promoted to Green at the next update.Created: 22 Jul 2026, 1:47 p.m. | Last Modified: 22 Jul 2026, 1:47 p.m.
Panel Version: 2.5
PMID: 41524020 Zhang et al., 2026
Cohort of patients with isolated congenital ptosis. Seq method: WES. Three novel heterozygous variants in ZFHX4, c.5145C>A (p.N1715K), c.10382C>T (p.A3461V), and c.10795G>A (p.A3599T), were identified in three patients of Han Chinese origin.
PMID: 32962661 Adhikari et al., 2020
Report of a Nepalese proband with congenital ptosis and a c.12411G>T, p.Leu4137Phe variant in exon 12 of ZFHX4.
Same variant reported in a Japanese kindred with hereditary congenital blepharoptosis (PMID: 17987257, Nakashima et al., 2008).
PMID: 11935336 McMullan et al., 2002
Report of a patient with congenital bilateral isolated ptosis and a de novo balanced translocation 46,XY,t(1;8)(p34.3;q21.12). The 1p breakpoint does not disrupt a coding sequence, whereas the chromosome 8 breakpoint disrupts the ZFHX4 gene.
This gene is not yet associated with a disease entity in OMIM. ZFHX4 association with AD syndromic complex neurodevelopmental disorder was classified as Strong in ClinGen in December 2025 (Intellectual Disability and Autism GCEP).Created: 22 Jul 2026, 1:41 p.m. | Last Modified: 22 Jul 2026, 1:46 p.m.
Panel Version: 2.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
congenital ptosis, MONDO:0008340
Publications
Nicky Cronbach (UCL/Moorfields Eye Hospital)
Multiple unrelated cases of isolated congenital ptosis reported. Three unrelated Han-Chinese patients (PMID 41524020) and one Nepalese patient (32962661) with missense variants in ZFHX4, and one case (unspecified ethnicity) related to a translocation disrupting ZFHX4.
Sources: LiteratureCreated: 26 Jun 2026, 11:21 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Isolated congenital ptosis
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Amber
- Phenotypes
-
- congenital ptosis, MONDO:0008340
- Tags
- OMIM
- 606940
- Clinvar variants
- Variants in ZFHX4
- Penetrance
- unknown
- Publications
- Panels with this gene
History Filter Activity
Removed Tag, Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q3_26_expert_review was removed from gene: ZFHX4. Tag Q3_26_NHS_review tag was added to gene: ZFHX4.
Added Tag, Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q3_26_expert_review tag was added to gene: ZFHX4. Tag Q3_26_promote_green tag was added to gene: ZFHX4.
Set Phenotypes
Ida Ertmanska (Genomics England Curator)Phenotypes for gene: ZFHX4 were changed from Isolated congenital ptosis to congenital ptosis, MONDO:0008340
Set publications
Ida Ertmanska (Genomics England Curator)Publications for gene: ZFHX4 were set to PMID: 41524020; 11935336; 32962661
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance
Nicky Cronbach (UCL/Moorfields Eye Hospital)gene: ZFHX4 was added gene: ZFHX4 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZFHX4 were set to PMID: 41524020; 11935336; 32962661 Phenotypes for gene: ZFHX4 were set to Isolated congenital ptosis Penetrance for gene: ZFHX4 were set to unknown Review for gene: ZFHX4 was set to GREEN