Nance-Horan Syndrome: Characterization of dental, clinical and molecular features in three new families

Abstract

Abstract Background: Nance–Horan syndrome (NHS; MIM 302350) is an extremely rare X-linked dominant disease characterized by ocular and dental anomalies, intellectual disability, and facial dysmorphic features. Case presentation: We report on five affected males and two symptomatic females from three unrelated NHS families. The clinical diagnosis in patient 1 (P1) was confirmed by targeted Sanger sequencing. Patient 2 (P2), boy aged 6 months, was evaluated due to preliminary diagnosis of syndromic microphthalmia and 300KSNP-array was performed. In family 3 (F3), two maternal half-brothers (P3 and P4) and their maternal uncle (P5), X-linked inheritance was sought for and Duo-WES was planned. P1 showing bilateral cataracts, iris heterochromia, microcornea, mild intellectual disability, and dental findings including Hutchinson incisors, supernumerary teeth, bud-shaped molars carried a novel pathogenic variant, c. 2416C>T; p.(Gln806*). P2 presenting with global developmental delay, microphthalmia, cataracts, and ventricular septal defect revealed a novel deletion encompassing 22 genes including the NHS gene. His lower incisors were in screwdriver shaped. P3, P4 and P5 had history of congenital cataracts and mild-moderate intellectual deficiency. Additionally, P3 displayed autistic and psychobehavioral features. Half-brothers had bud-shaped molars. P4 also presented with notched incisors, bud-shaped permanent molars, and supernumerary molars. Duo-WES analysis on half-brothers showed a hemizygous novel deletion, c.1867delC; p.(Gln623ArgfsTer26). Conclusions: Our findings not only broaden the spectrum of genetic etiopathogenesis associated with NHS but also highlight the importance of dental professionals to be made aware of the features. Dental professional could be the first specialist involved in the diagnosis of NHS since dental findings are highly distinctive for this syndrome.