NDP- Related Retinopathies

Excerpt

Clinical characteristics: NDP-related retinopathies typically involve bilateral and symmetric fibrovascular changes of the retina that are evident at birth and usually progress through childhood or adolescence to cause varying degrees of visual impairment. The spectrum of NDP-related retinopathies appears to be a continuum with considerable overlap, ranging from Norrie disease, NDP-related persistent fetal vasculature, NDP-related familial exudative vitreoretinopathy, NDP-related advanced retinopathy of prematurity, and NDP-related Coats disease. The eye findings of Norrie disease, the first described and best characterized of these disorders, are typically bilateral grayish-yellow, glistening, elevated retrolental masses composed of immature retinal cells usually visible through clear lenses; foveal development is always incomplete. In addition, Norrie disease is the only NDP-related retinopathy with associated extraocular findings, which can variably include cognitive disability, mental health and behavior disorders, seizures, sensorineural hearing loss, and peripheral vascular disease.

Rarely, females who are heterozygous for an NDP pathogenic variant have clinical manifestations including retinal and extraocular features that may vary between other family members heterozygous for the same NDP pathogenic variant.

Diagnosis/testing: The diagnosis of an NDP-related retinopathy, an X-linked disorder, is established in a male proband with suggestive clinical findings by identification on molecular genetic testing of a hemizygous pathogenic variant in NDP; and in a female proband with suggestive clinical findings by identification of a heterozygous pathogenic variant in NDP.

Management: Treatment of manifestations: Based on a child's ocular findings, pediatric ophthalmologists and pediatric vitreoretinal surgeons individualize management to reduce increased intraocular pressure to decrease the risk of glaucoma; treat refractive errors and/or strabismus to optimize vision and ocular alignment; and discuss risks and benefits of possible vision-saving surgical intervention. Other issues are addressed by multidisciplinary specialists, typically: low-vision specialists, neurologists, pediatricians, developmental pediatricians, pediatric sleep specialists, mental health specialists, physiatrists, occupational and physical therapists, audiologists, and speech-language pathologists.

Surveillance: Routine monitoring of: ophthalmologic manifestations and low vision needs; hearing; developmental progress and educational needs; neurologic and mental health manifestations; peripheral vascular disease; and response to treatment.

Agents/circumstances to avoid: Situations that could exacerbate hearing loss such as loud noises and use of listening devices that amplify sound.

Evaluation of relatives at risk: Clarify the genetic status of apparently asymptomatic older and younger at-risk female relatives so that those with the familial NDP pathogenic have the option to undergo fluorescein angiography to detect peripheral retinal vascular changes that may require close monitoring and/or prophylactic laser photocoagulation to decrease the risk of neovascularization and vitreoretinal traction.

Genetic counseling: NDP-related retinopathies are inherited in an X-linked manner. The majority of affected males have the disorder as the result of an NDP pathogenic variant inherited from their mother. If the mother of the proband has an NDP pathogenic variant (i.e., is a carrier), the chance of transmitting it in each pregnancy is 50%: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygous and may rarely have clinical manifestations. Affected males transmit the NDP pathogenic variant to all of their daughters and none of their sons. Once the NDP pathogenic variant has been identified in an affected family member, testing for females at risk of being carriers and prenatal and preimplantation genetic testing are possible.