NDP gene

• Overview
• Norrie disease
• Additional information
• References

Overview

Gene (OMIM No.)	NDP (#300658)
Function of gene/protein	Protein: Norrin Part of the Wnt signalling pathway Ligand of FZD4 receptor Involved in the normal development of vascular endothelium in the retina and inner ear Dysfunction leads to poor blood-retinal barrier in the retina
Clinical phenotype (OMIM phenotype no.)	Exudative vitreoretinopathy 2 (#305390) Norrie disease (#310600)
Inheritance	X-linked recessive (Norrie disease and exudative vitreoretinopathy) X-linked dominant (exudative vitreoretinopathy)
Ocular features	Familial exudative vitreoretinopathy (FEVR) of variable severity Leukocoria Retinal folds extending from temporally from the disc to the anterior periphery Macula dragging Retinal neovascularisation Retinal detachments Retrolental mass of dysplastic and primitive retinal tissues Retinal detachments More severe phenotype in Norrie disease Cataract and microphthalmia common in Norrie disease
Systemic features	Norrie disease Progressive sensorineural hearing loss Developmental delays Neurological deficits (more common in chromosomal deletions involving the MAOA and MAOB genes Autonomic and endocrine dysfunction (delayed puberty, short stature, sexual dysfunction) Peripheral vascular dysfunction (varicose veins, leg ulcers)
Key investigations	Fluorescein angiography to determine areas of non-perfusion in the peripheral retina Electrophysiology to determine visual potential B-scan USS to identify any posterior segment abnormalities (e.g retinal detachment) if presence of retrolental mass prevents a detailed fundal examination Developmental assessment Audiometry
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing Whole genome sequencing
Management	Laser to all areas of non-perfusion especially in eyes with visual potential Retinal detachments should be treated with an encircling buckle instead of a vitrectomy where possible; vitrectomy may be required for posterior breaks Management is usually supportive in Norrie disease due to the advanced retinal detachment at initial presentation Multidisciplinary approach in Norrie disease Routine audiology testing and hearing aids if hearing loss is present
Therapies under research	Gene therapy for Norrie disease (pre-clinical)
Further information	Medline Plus

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Additional information

NDP deletion and truncation mutations lead to Norrie disease, while missense variants are associated with Norrie disease or exudative vitreoretinopathy.^[8]

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References

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