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Persistent hyperplastic primary vitreous
PHPV affects the development of vision in infants, often in one eye, and can lead to significant visual impairment. Early detection and management are important to improve visual outcomes for affected children.
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Overview
Persistent hyperplastic primary vitreous (PHPV) is a rare congenital eye condition, meaning it is present from birth. It results from the failure of a network of embryonic blood vessels, called the primary vitreous, to properly shrink and disappear during foetal development. This primary vitreous is normally present in the eye during early development but should regress by the time a baby is born. When it persists and becomes hyperplastic (overgrown), it can interfere with normal eye development and cause various visual problems [PMID:33678587].
PHPV most commonly affects one eye (unilateral), but in some instances, both eyes (bilateral) can be involved. The severity of PHPV can vary significantly, ranging from mild forms with limited impact on vision to severe forms that can lead to profound visual impairment. It is typically diagnosed in infancy or early childhood when parents or healthcare professionals notice unusual eye signs or visual difficulties.
Symptoms & clinical features
The symptoms of persistent hyperplastic primary vitreous can vary depending on the extent and location of the persistent tissue. Parents might notice a white reflection in their child's pupil, which is often referred to as 'leukocoria' [PMID:33678587]. This can be particularly noticeable in photographs taken with a flash. The affected eye may also appear smaller than the unaffected eye, a condition known as microphthalmia, or the eye may move abnormally.
Other signs can include strabismus (misalignment of the eyes), nystagmus (involuntary eye movements), or an opacity (cloudiness) of the lens, similar to a cataract. In more severe cases, complications like glaucoma (increased pressure within the eye) or retinal detachment can occur, which can further impact vision. The specific clinical presentation often guides diagnostic investigations and subsequent management.
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Affected organs
Persistent hyperplastic primary vitreous primarily affects the eye. Specifically, it impacts the vitreous humour (the clear jelly-like substance that fills the centre of the eye), the lens, and potentially the retina. The persistent embryonic tissue can draw the ciliary body and lens backwards, causing the lens to become cloudy (cataract) or dislocated. It can also pull on the retina, potentially leading to a retinal detachment.
The abnormal blood vessels and fibrous tissue can also obstruct the normal drainage of fluid within the eye, contributing to the development of glaucoma. While the condition is localised to the eye, the resulting visual impairment can impact a child's overall development and learning, necessitating early intervention.
Risks & severity
PHPV presents a spectrum of severity, from mild cases with minimal visual impact to severe forms causing significant, irreversible vision loss. The long-term visual outcome largely depends on the specific type of PHPV, whether it affects one or both eyes, and how early it is diagnosed and managed. If untreated, severe PHPV can lead to blindness in the affected eye due to complications like retinal detachment, glaucoma, or severe amblyopia (lazy eye) [PMID:27063137].
There isn't a specific age of onset for PHPV as it is congenital. However, complications and their impact on vision tend to progress over time if left unmanaged. While PHPV itself is rare, its association with other genetic conditions can influence the overall health risks for an affected individual. The exact prevalence of PHPV is not well established, but it is considered a rare disorder.
Genetic causes
Persistent hyperplastic primary vitreous is a clinically heterogeneous condition, meaning it can arise from various causes. While many cases are sporadic (occurring by chance with no clear genetic link), some forms of PHPV have a genetic basis. Pathogenic variants in the NDP gene are one known genetic cause [PMID:27063137].
The NDP gene provides instructions for making the norrin protein, which plays a crucial role in the development of blood vessels in the retina, the light-sensitive tissue at the back of the eye. Norrin is a signalling molecule vital for cellular development and communication. When the NDP gene has a pathogenic variant, the norrin protein may not function correctly, leading to abnormal retinal vascular development and sometimes persistent embryonic vessels, contributing to the features seen in PHPV. Other genes may also be implicated, but NDP is a well-established cause for some forms.
- NDP norrin cystine knot growth factor NDPThe NDP gene provides instructions for making the norrin protein, which is crucial for normal eye development, particularly retinal specialisation and blood vessel formation in the retina and inner ear.
Inheritance pattern
Persistent hyperplastic primary vitreous can be inherited in different ways, including autosomal dominant (AD) and autosomal recessive (AR) patterns. In autosomal dominant inheritance, only one copy of a gene with a pathogenic variant is needed to cause the condition. This means an affected parent has a 50% chance of passing on the variant to each child.
In autosomal recessive inheritance, a person must inherit two copies of the gene with a pathogenic variant (one from each parent) to develop the condition. Parents who each carry one copy of the pathogenic variant are typically unaffected themselves, but they have a 25% chance with each pregnancy of having a child with the condition. The inheritance pattern can influence genetic counselling and family planning decisions for affected families.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of persistent hyperplastic primary vitreous typically begins with a thorough clinical eye examination by a paediatric ophthalmologist. This often involves dilating the pupils to allow for a detailed view of the back of the eye. Imaging techniques such as ocular ultrasonography are commonly used to visualise the persistent tissue, assess the presence of retinal detachment, and evaluate the overall structure of the eye [PMID:33678587].
If a genetic cause is suspected, or if the PHPV is part of a broader syndrome, genetic testing may be offered. Referrals for genetic testing in the UK can be initiated by a specialist clinician, such as a paediatric ophthalmologist or a clinical geneticist. This testing would fall under the NHS Genomic Medicine Service, potentially utilising an R-code for inherited eye disorders, to identify specific gene variants, such as in NDP, that might be contributing to the condition.
Management & lifestyle
The management of persistent hyperplastic primary vitreous focuses on preserving and improving vision, and preventing complications. Early surgical intervention is often considered to remove the persistent fibrous and vascular tissue, address cataracts, and reattach a detached retina. The timing and type of surgery depend on the severity and specific features of the PHPV [PMID:27063137].
Following surgery, aggressive amblyopia (lazy eye) treatment, which might include patching the unaffected eye, is crucial to encourage the development of vision in the affected eye. Long-term follow-up with a paediatric ophthalmologist is essential to monitor for potential complications like glaucoma, which may require ongoing medical or surgical treatment. Management plans are individualised and developed by a multidisciplinary team.
UK care pathway
In the UK, individuals suspected of having persistent hyperplastic primary vitreous would typically enter the NHS Genomic Medicine Service pathway. This often begins with a referral from a GP or an optometrist to a specialist paediatric ophthalmologist. If a genetic cause is suspected, the ophthalmologist may refer to a clinical genetics service.
Clinical geneticists and genetic counsellors provide comprehensive support, including confirming a diagnosis through genetic testing (using relevant R-codes for inherited eye conditions), explaining inheritance patterns, and discussing implications for other family members. They also help families navigate the complex medical and social support systems available within the NHS.
Frequently asked questions
What does 'congenital' mean for PHPV?
'Congenital' means that persistent hyperplastic primary vitreous is present at birth. It develops during foetal development because the primary vitreous, a network of blood vessels, does not disappear as it should.
Can PHPV affect both eyes?
PHPV most commonly affects only one eye (unilateral), but in some cases, both eyes (bilateral) can be involved. The impact on vision can differ between the two eyes.
What is the white reflection in the eye mentioned for PHPV?
The white reflection is called leukocoria. It's a common sign of PHPV and occurs when light reflects off the abnormal tissue inside the eye. It can be noticeable in flash photographs.
Is PHPV always inherited?
No, PHPV is not always inherited. Many cases are sporadic, meaning they happen by chance without a clear genetic cause. However, some forms can be inherited in an autosomal dominant or autosomal recessive pattern, particularly when specific genes like NDP are involved.
What kind of doctor treats PHPV in the UK?
In the UK, PHPV is primarily treated by a paediatric ophthalmologist, who specialises in children's eye conditions. If a genetic cause is suspected, a clinical geneticist will also be involved in the care.