Atypical Norrie disease due to Xp11.3 microdeletion

Atypical Norrie disease due to Xp11.3 microdeletion is a rare X-linked genetic condition caused by a contiguous gene deletion on the short arm of the X chromosome at position Xp11.3, which encompasses the NDP gene (responsible for classic Norrie disease) along with neighboring genes such as MAOA and MAOB (monoamine oxidase A and B). Because the deletion extends beyond the NDP gene alone, affected individuals present with the characteristic ocular features of Norrie disease — including congenital bilateral blindness due to retinal dysplasia, retinal detachment, and vitreous opacities — but also exhibit additional systemic features not typically seen in classic Norrie disease. These additional features may include severe intellectual disability, behavioral disturbances, and growth abnormalities, reflecting the loss of adjacent genes in the microdeletion. The ocular manifestations are typically present at birth or in early infancy, with progressive retinal changes leading to complete blindness. Sensorineural hearing loss may also develop over time, as seen in classic Norrie disease. The involvement of the MAOA and MAOB genes can contribute to significant neurobehavioral abnormalities, including aggressive or impulsive behavior, which distinguishes this contiguous gene deletion syndrome from isolated Norrie disease. Some patients may also exhibit features of monoamine oxidase deficiency, such as abnormal neurotransmitter metabolism. There is currently no cure for atypical Norrie disease due to Xp11.3 microdeletion. Management is supportive and multidisciplinary, involving ophthalmologic care, audiological monitoring and hearing aids or cochlear implants for progressive hearing loss, developmental and behavioral interventions, and educational support for visual impairment. Genetic counseling is important for affected families given the X-linked inheritance pattern.

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