Corneal dystrophy

Gene: AP1B1

I don't know

Comment on list classification: While there are at least 4 reported unrelated individuals with photophobia and / or corneal scarring attributed to biallelic variants in AP1B1, in depth ophthalmologic examination and disease mechanism are lacking. Photophobia is only seen in a subset of Keratitis-ichthyosis-deafness syndrome patients. Hence, the gene is rated Amber for Corneal dystrophy.

Created: 17 Oct 2025, 4:11 p.m. | Last Modified: 17 Oct 2025, 4:11 p.m.

Panel Version: 4.3

PMID: 31630788 Boyden et al., 2019
Individual 424, adult male, born with normal skin; diagnosed with ichthyosis at 2 months old; developmental delay, growth delay, partial hearing loss, tooth loss, profound photophobia, and
corneal scarring leading to near complete vision loss. At age 33 had erythroderma with thin palmoplantar
keratoderma, and a fissured tongue; noted thickening of his palms and soles since childhood.

PMID: 33452671 Vornweg et al., 2021
Female patient with compound het mutations in AP1B1: c.322C>T (p. Arg108Trp) and c.2254delC (p.Leu752Serfs*26). Method: WES + Sanger. Presented with ichthyosiform erythroderma and chronic, severe pruritus from birth; global developmental delay and failure to thrive, thickened plantar surface, bilateral ectropion and partial alopecia; developed bilateral deafness and moderate photophobia.

PMID: 32969855 Meriç et al., 2021
11mo Turkish girl; consanguineous parents. Homozygous for (AP1B1:NM_001127) c.668T>C, p.Leu223Pro - WES. Presented with ichthyosis and developmental delay. Other symptoms: hearing loss, hepatomegaly, chronic diarrhea, partial alopecia, hyperkeratosis; eye examination showed photophobia and high myopia.

PMID: 35144013 Faghihi et al., 2022
Proband: 6.5yr old boy, consanguineous parents. Homozygous for AP1B1 (NM_001127.4: c.1263C>A, p.Tyr421*) - WES. Presented with developmental delay, keratitis, ichthyosis, hearing loss, palmoplantar keratoderma, sparse hair, erythroderma; ophthalmologic examination: photophobia, corneal scarring, and eyelid swelling.

AP1B1 is associated with Keratitis-ichthyosis-deafness syndrome, autosomal recessive, 242150 in OMIM (accessed 17th Oct 2025).
This gene was classified as Definitive for AR ichthyosiform erythroderma, corneal involvement, and hearing loss by ClinGen (General Inborn Errors of Metabolism Expert Panel, Aug 2024).

Created: 17 Oct 2025, 4:08 p.m. | Last Modified: 17 Oct 2025, 4:26 p.m.

Panel Version: 4.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Keratitis-ichthyosis-deafness syndrome, autosomal recessive, OMIM:242150; KID syndrome, MONDO:0018781

Publications

• 31630788
• 33452671
• 32969855
• 35144013