Ectodermal dysplasia

Gene: ANTXR1

Green List (high evidence)

Comment on list classification: There are over a 100 individuals reported with GAPO syndrome and biallelic ANTXR1 variants. Ectodermal dysplasia, including alopecia, and sparse dentition, is a primary feature of this syndrome. Hence, this gene should be rated Green on Ectodermal dysplasia.

Created: 23 Oct 2026, 10:10 a.m. | Last Modified: 23 Oct 2026, 10:10 a.m.

Panel Version: 5.12

PMID: 40962491 Modafferi et al., 2025
Review of 105 GAPO syndrome cases + new case: report of a 33yo woman with GAPO syndrome a homozygous ANTXR1 deletion of exons 4, 5, and 6. The newly reported individual had short stature (130cm), craniofacial abnormalities, absence of several dental elements, liver disease/hepatomegaly, blindness secondary to optic atrophy, alopecia, primary amenorrhea, and progeroid appearance of the skin.
Literature review describes a common phenotype: growth impairment, alopecia, sparse dentition (97/105), long bone dysplasia, optic atrophy (48/105) & other ocular features. Intellectual disability is not a common feature of this syndrome - cognitive function was explicitly reported to be normal in 27 cases, and not mentioned in others.
Both missense, splice, and frameshift variants in ANTXR1 have been reported to cause GAPO syndrome.

PMID: 38423276 Balakrishnan, Goud, & Teegala, 2024
Report of an Indian proband, 3.75yrs old female, with GAPO syndrome. She presented with short stature, reduced length of long bones, dysmorphism, sparse hair growth & lack of appropriate dentition. She was born with sagittal craniosynostosis and right club foot. Patient was noted to have mild dev delay with preserved intellect and social skills. Her head circumference was 49.5 cms (-1.1 Z score), height was 82 cms (−4.5 Z score). Trio exome detected a homozygous ANTXR1 NM_032208.3: c.568delC (p. Arg190GlyfsTer12) variant in the proband - het in parents.

PMID: 30575274 Abdel-Hamid et al., 2019
Report of 7 patients from 5 unrelated consanguineous Egyptian families with GAPO syndrome and ANTXR1 variants. Common phenotype: alopecia, pseudoadontia, micrognathia, dysmorphism (e.g., frontal bossing, hypertelorism) optic atrophy (6/7), glaucoma (unilateral or bilateral), short stature, microcephaly (7/7, including 3 unrelated patients with severe microcephaly of more than -3 SD), joint hyperextensibility. Craniosynostosis and keratopathy noted in only 1/7 individuals. Intellectual disability not reported.
Individuals harboured 5 different homozygous ANTXR1 variants: 2 splice variants, 2 frameshift variants, and 1 deletion. Their parents were heterozygous and unaffected.

ANTXR1 association with AR GAPO syndrome is classified as Definitive in ClinGen (Syndromic Disorders GCEP, July 2025). This gene is associated with AR GAPO syndrome, OMIM:230740 in OMIM (accessed 23rd Oct 2026).
Sources: Literature

Created: 23 Oct 2026, 10:07 a.m. | Last Modified: 23 Oct 2026, 10:12 a.m.

Panel Version: 5.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
GAPO syndrome, OMIM:230740; GAPO syndrome, MONDO:0009263; Growth delay-alopecia-pseudoanodontia-optic atrophy syndrome

Publications

• 30575274
• 38423276
• 40962491