Xeroderma pigmentosum: Image, symptoms, therapy, and further information
Xeroderma pigmentosum (XP), a rare genetic disorder, is primarily known for its severe sun sensitivity and the elevated risk of skin cancers it presents. However, XP also has significant neurological implications for some patients.
Approximately one-third of XP patients experience progressive neurodegeneration, a proportion that can vary by genetic subtype. Neurological symptoms can arise early in life, with some XP-A patients exhibiting developmental delays by the age of 2, and neurological symptoms presenting before dermatological signs.
Neurological deficits are typically progressive, often starting with developmental delays, ataxia, and sensorineural hearing loss, and may progress to spasticity, seizures, and cognitive decline. Developmental delay and intellectual disability are common, especially in early-onset cases, while ataxia (loss of coordination) and spasticity (muscle stiffness) are frequent findings as the disease progresses. Sensorineural hearing loss can occur, further complicating communication and cognitive development.
The severity of neurological involvement varies, but those with neurodegeneration have a significantly reduced life expectancy (median age at death ~29 years) compared to XP patients without neurological symptoms (median ~37 years). In addition to skin cancer, progressive neurological deterioration can be a direct cause of mortality in XP.
The neurological effects are due to defects in DNA repair mechanisms, specifically nucleotide excision repair (NER). The inability to repair DNA damage leads to neuronal cell death over time, particularly affecting the central and peripheral nervous systems. Some genetic mutations (e.g., in the XPG gene) can result in severe combined XP/Cockayne syndrome phenotypes, which may feature more pronounced neurological symptoms.
A summary table outlines the main features of neurological involvement in XP, including the prevalence, typical onset, progression, and notes for each feature.
In conclusion, long-term neurological effects in XP—most notably progressive neurodegeneration—occur in about one-third of patients and are a major determinant of morbidity and mortality. Early developmental delays, ataxia, spasticity, hearing loss, and cognitive decline are hallmarks of neurological involvement, with severity and progression varying by genetic subtype. Access to specialized multidisciplinary care may influence outcomes, but these neurological complications remain a significant challenge in the management of XP.
It is essential to note that XP is an autosomal recessive genetic disorder, meaning that both copies of the gene must have the characteristics of XP for the child to have the condition. The condition can develop anywhere, but it appears to be more common in some countries, such as Japan, where it affects 1 in 22,000 people. Cigarette smoke can cause DNA damage, so people with XP should avoid smoking and secondhand smoke. Approximately 1 in 1 million people in the United States have XP, and many people with XP have no family history of the condition.
Regular vision, hearing, and neurologic exams are necessary for people with XP, and they need to visit a dermatologist every 6-12 months for skin cancer screenings. Symptoms that affect the eyes occur in approximately 80% of people with XP and can include photophobia (light sensitivity), bloodshot and irritated eyes, cloudy corneas, dry eye, and keratitis (inflammation of the cornea). Protective clothing, UV light-blocking sunscreen, protective sunglasses, and UV light-blocking film on windows can help reduce UV light exposure. Repeated sun exposure may also affect the eyelids, causing them to thin and the eyelashes to fall out. People with XP should take vitamin D supplements as sunlight is a primary source of vitamin D.
A prompt and accurate diagnosis is crucial for managing XP symptoms and improving the outlook. People with XP have an increased chance of developing skin cancer, with a 1,000 times higher risk of nonmelanoma skin cancer and a 2,000 times greater risk of melanoma compared to the general population. Any area of skin that comes into contact with sunlight is susceptible to XP-related damage. Let a doctor know about any persistent signs of the condition.
- Neurological deficits in Xeroderma pigmentosum (XP) are primarily due to defects in the nucleotide excision repair (NER) mechanism, causing neuronal cell death over time.
- The neurological implications of XP can present early in life, such as developmental delays by the age of 2, even before dermatological signs become apparent.
- Neurological symptoms in XP, such as ataxia, spasticity, seizures, and cognitive decline, are progressive and can affect communication and cognitive development.
- The severity of neurological involvement in XP varies by genetic subtype, with some subtypes having a significantly reduced life expectancy (median age at death ~29 years).
- In addition to skin cancer, progressive neurological deterioration can be a direct cause of mortality in XP patients.
- Regular vision, hearing, and neurologic exams are essential for XP patients to help manage their neurological complications.
- Access to multidisciplinary care may influence outcomes for XP patients, but neurological complications remain a significant challenge in the management of XP.
- Mental health and sexual health are also important considerations for people with XP, as isolation and other psychosocial factors can impact their overall well-being.
- Nutrition and weight management are crucial for XP patients, as their unique skin sensitivity and potential malnutrition require specialized attention.
- Medicare and other insurance providers may cover some of the costs associated with the specialized care and therapies and treatments required for XP patients, such as CBD oil, which is commonly used to manage neurological symptoms in some cases.
