Paediatric disorders - additional genes

Gene: CDH11

Green List (high evidence)

Comment on list classification: There are multiple individuals reported in literature with heterozygous missense variants in CDH11 and Teebi hypertelorism syndrome. The syndrome is characterised by hypertelorism, cardiac and genitourinary defects. Other more variable features include digital anomalies and developmental delay. Based on available evidence, this gene can be rated Green on Paediatric disorders - additional genes. The recessive association with Elsahy-Waters syndrome is already reflected in a Green rating on Intellectual disability.

Created: 28 Oct 2026, 5:22 p.m. | Last Modified: 28 Oct 2026, 5:22 p.m.

Panel Version: 8.23

PMID: 37646430 Kuroda et al., 2023
Report of a 10-month-old Japanese male with a syndromic presentation but normal developmental milestones. He had widely spaced eyes, strabismus, hypospadias, shawl scrotum, broad thumbs (right bifid thumb in x-ray), polysyndactyly of the left fourth finger, and cutaneous syndactyly of left third/fourth fingers. Exome sequencing identified a de novo heterozygous CDH11 variant NM_001797.4:c.229C > T, p.Leu77Phe.

PMID:33811546 Li et al., 2021
Report of 19 subjects from 9 families with Teebi hypertelorism syndrome (hypertelorism, prominent forehead, short nose, broad/depressed nasal root, cardiac and umbilical defects). Patients had heterozygous missense variants affecting residues in the extracellular region of CDH11. Immunohistochemical study demonstrated that CDH11 is strongly expressed in human facial mesenchyme. Using multiple functional assays, they showed 5 variants significantly reduced the cell-substrate trans adhesion activity and changed cell morphology, focal adhesion, and migration, suggesting dominant negative effect. 37% of Teebi cohort had ID: 7/19 cases (4 families) presented a developmental phenotype including very mild speech delays in 5/7, mild-moderate DD in 1/7, and global delay in 1/7 individuals. All variants were missense.

Association between CDH11 and AD Teebi hypertelorism syndrome 2 has been classified as Moderate in ClinGen (Syndromic Disorders GCEP, May 2024). This gene is associated with AD Teebi hypertelorism syndrome 2 OMIM:619736 and AR Elsahy-Waters syndrome, OMIM:211380. Resources accessed 28th Oct 2026.
Sources: Literature

Created: 28 Oct 2026, 5:16 p.m. | Last Modified: 28 Oct 2026, 5:18 p.m.

Panel Version: 8.22

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Teebi hypertelorism syndrome 2, OMIM:619736; Teebi hypertelorism syndrome 2, MONDO:0030674

Publications

• 33811546
• 37646430

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments