PAX1gene pathogenic variants are now known to cause disease either through biallelic or monoallelic variants. The phenotype associated with biallelic pathogenic variants of PAX1gene is otofaciocervical syndrome type 2 with variable T-cell immunodeficiency. Whereas monoallelic pathogenic variants may be associated with oculo-auriculo-vertebral syndrome or otofaciocervical syndrome 2 phenotypes suggestive of autosomal dominant pattern of inheritance as well.
Earlier autosomal dominant form of otofaciocervical syndrome (labelled as otofaciocervical syndrome type 1) has been reported to be caused by monoallelic pathogenic variants in EYA1gene.
The otofaciocervical syndrome type 2 is a multisystem disorder characterized by ear malformations (external/middle/inner ear), facial dysmorphism, skeletal abnormalities (shoulder girdle abnormalities, kyphosis, scoliosis, vertebral anomalies), hearing loss, hypoparathyroidism, variable intellectual disability, and variable immunodeficiency.
Not all individuals with a mutation in the PAX1gene have these features.
So far 17 affected individuals with autosomal recessive OTFCS type 2 have been reported from 13 families worldwide.
PAX1