Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity

Abstract

Background: Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry.

Materials and Methods: Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis.

Results: A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant.

Conclusions: HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.

• Hereditary benign intraepithelial dyskeratosis
• NLRP1
• segment duplication

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

Support provided by National Eye Institute grants 1R01 EY022082 (A.J.A.) and P30 EY000331 (core grant), and an unrestricted grant from Research to Prevent Blindness (A.J.A.). Funding for the Undiagnosed Diseases program is through the NIH Interinstitute Common Fund, Office of the Director, NIH, Bethesda, Maryland.