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

BACKGROUND: Nance–Horan syndrome (NHS; MIM 302,350) 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 three carrier females from three unrelated NHS families. In Family 1, index (P1) showing bilateral cataracts, iris heterochromia, microcornea, mild intellectual disability, and dental findings including Hutchinson incisors, supernumerary teeth, bud-shaped molars received clinical diagnosis of NHS and targeted NHS gene sequencing revealed a novel pathogenic variant, c.2416 C > T; p.(Gln806*). In Family 2, index (P2) presenting with global developmental delay, microphthalmia, cataracts, and ventricular septal defect underwent SNP array testing and a novel deletion encompassing 22 genes including the NHS gene was detected. In Family 3, two half-brothers (P3 and P4) and maternal uncle (P5) had congenital cataracts and mild to moderate intellectual deficiency. P3 also had autistic and psychobehavioral features. Dental findings included 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: Dental professionals can be the first-line specialists involved in the diagnosis of NHS due to its distinct dental findings. Our findings broaden the spectrum of genetic etiopathogenesis associated with NHS and aim to raise awareness among dental professionals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12903-023-03029-4.