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 conjuctival 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: Is this the first African case?

“…IBID is a hereditary condition, the symptoms of which appear in early childhood and predominantly affecting descendents of Haliwa-Saponi Native Americans [2]. They appear as whitish, painless, spongy papules or plaques of varying sizes, reaching any part of the oral cavity.…”

“…The genetic study makes it easy to retain the diagnosis (duplication 4q35), but is not essential [4]. Several medical and surgical treatments have been proposed, but none has proved quite effective [2]. MRS is a rare disorder consisting of a triad of persistent or recurrent orofacial edema, relapsing facial paralysis and fissured tongue.…”

Oral White Lesions: An Updated Clinical Diagnostic Decision Tree

“…This condition primarily reported in descendants of tri-racial isolate (European-American, African-American, and Native American descents) in North Carolina; however, some examples of HBID have been reported sporadically from other areas of the United States, which might be due to migration of affected people. On the other hand, no history of migration to the United States was found in some patients [5,12]. This disorder progresses during childhood with oral manifestations being similar to WSN as thick, corrugated white plaques affecting the buccal and labial mucosa.…”

“…In many cases, the plaques are more obvious in the spring, but they show seasonal regression during summer or autumn. Corneal involvement can result in visual impairment and blindness [5,10,12]. Hereditary benign intraepithelial dyskeratosis is a benign lesion in the oral cavity; hence no treatment modality is needed unless a superimposed infection with candida occurs, which requires antifungal therapy.…”

Oral Mucosal White Lesions

“…Konjunktival epitelyal plakların kornea üzerine uzandığı durumlarda, görme etkilenebilir ve korneal transplantasyon gerekebilir. 34 Ayrıcı tanısında beyaz süngersi nevus düşünülmelidir fakat konjunktiva tutulması ayırıcı tanıya yardımcı bir bulgudur. 26 Bu hastaların ağız mukozasındaki beyaz lezyonlar tedavi gerektirmez fakat konjuktival epitelyal plaklar ilerleyen olgularda görme kaybına neden olduğundan erken tanı önemlidir.…”