Examination Recommendations for Norrie Disease and Incontinentia Pigmenti
Norrie Disease: Essential Ocular and Systemic Examinations
Patients with Norrie disease require comprehensive ophthalmologic evaluation focusing on the characteristic bilateral retinal malformation, progressive ocular complications, and associated systemic manifestations including hearing loss and neurologic involvement. 1, 2
Primary Ocular Examination Components
Slit-lamp biomicroscopy to identify the pathognomonic dense, white, vascularized retrolental mass present in early life, representing maldeveloped retina from developmental arrest in the middle embryonic stage 1
Assessment for cataracts and corneal opacities, which typically develop in young childhood as part of the progressive disease course 1
Evaluation for bulbar atrophy, which follows the earlier ocular manifestations and represents advanced disease 1
Fundus examination (when possible through media opacities) to document retinal malformation and vitreoretinal dysplasia 1, 2
Intraocular pressure measurement to monitor for secondary glaucoma complications 2
Systemic Evaluation Requirements
Audiologic assessment for progressive sensorineural hearing loss, which occurs in approximately 20-25% of affected males 1, 3
Neurologic and developmental evaluation to identify psychomotor retardation or mental deterioration, present in approximately 25% of cases 1, 3
Genetic testing for mutations in the Norrie disease gene (NDP), which encompasses 27 kilobases with three exons; molecular diagnosis can identify microdeletions and point mutations 1
Key Differential Diagnoses to Exclude
The examination must distinguish Norrie disease from: retinoblastoma, retrolental fibroplasia, toxoplasmosis, falciform detachment, juvenile retinoschisis, X-linked microphthalmia, X-linked cataract, and congenital retinal detachment 3
Incontinentia Pigmenti: Multisystem Examination Protocol
Incontinentia pigmenti requires systematic evaluation of ocular, dental, cardiac, and neurologic structures, with particular attention to retinal vascular abnormalities that can mimic other X-linked vitreoretinopathies. 4
Comprehensive Ocular Assessment
Dilated fundus examination to identify retinal vascular abnormalities, including areas of nonperfusion and neovascularization that resemble familial exudative vitreoretinopathy 4
Retinal vascular imaging (fluorescein angiography when indicated) to document peripheral retinal ischemia and vascular closure patterns 4
Assessment for retinal detachment, which represents a severe complication requiring urgent intervention 4
Slit-lamp examination to evaluate anterior segment structures and identify any associated abnormalities 4
Systemic Examination Components
Dermatologic evaluation for the characteristic skin manifestations progressing through vesicular, verrucous, hyperpigmented, and hypopigmented stages 4
Dental assessment for abnormalities including delayed eruption, missing teeth, and conical tooth shape 4
Cardiac evaluation to identify structural abnormalities that may be present in this multisystem disorder 4
Neurologic examination to detect central nervous system involvement, which can include developmental delays, seizures, or other neurologic deficits 4
Critical Distinction from Norrie Disease
While the retinal pathology in incontinentia pigmenti can appear similar to X-linked familial exudative vitreoretinopathy, genetic analysis has demonstrated that mutations in the Norrie disease gene do not account for the retinal findings in IP, indicating distinct genetic mechanisms 4
Genetic Counseling Considerations
Family history documentation is essential for both conditions, as Norrie disease follows X-linked recessive inheritance with 50% risk for sons of female carriers 1
Carrier detection through genetic testing should be offered to at-risk female relatives in families with Norrie disease 1
Molecular diagnosis is now available for Norrie disease, though genotype-phenotype correlation remains incompletely defined 1