Epidermal nevus syndrome is more than skin deep. Although characterised by a distinct appearance, epidermal nevus syndrome can cause significant neurological issues. The most significant neurological complications include seizures, developmental delays, abnormalities in brain structure and fluid in the brain. These can all impact growth and quality of life, but can be managed with timely diagnosis and treatment. 

Read on to find out more about this condition and its neurological complications in more detail. 

Introduction

Epidermal nevus syndrome is a term used to describe a series of conditions that affect the skin, namely the presence of skin growths or lesions called epidermal nevi. Although it may seem like a “skin deep” condition, epidermal nevus syndrome can come with a share of symptoms that affect other parts of the body, including the brain.¹ The individual syndromes that come under the umbrella term of epidermal nevus syndrome include:

• Schimmelpenning syndrome²
• Phakomatosis pigmentokeratotica 
• Nevus comedonicus syndrome
• Becker nevus syndrome
• Proteus syndrome
• CHILD syndrome

The location of the nevi is associated with any additional symptoms. For example, when epidermal nevi appear on the head or face, they are more often associated with symptoms involving the brain, eyes and skull. When nevi are located on the back and trunk, they tend to be paired with problems like curvature of the spine, hip abnormalities or deformities of the limbs. 

How does epidermal nevus syndrome arise?

Epidermal nevus syndrome is a genetic condition which arises due to mutations in the genetic code that occur in the womb after fertilisation (the process in which the egg and sperm meet). This leads to some cells and organs being affected and others not. 

Common neurological complications in epidermal nevus syndrome 

Below are some of the more common neurological complications associated with epidermal nevus syndrome and their treatment options. 

Seizures

Seizures are one of the most commonly observed neurological complications seen in those with epidermal nevus syndrome. These seizures occur due to structural abnormalities in the brain like brain enlargement or asymmetry.³ Changes in the structure of the brain can lead to abnormal brain signalling, which presents in different types of seizures like focal impaired awareness seizures, atonic seizures or myoclonic seizures.⁴ 

Whilst some patients respond well to traditional anti-seizure medications, in some cases seizures are treatment-resistant and may require additional approaches.4 In the case of treatment-resistant seizures, specific surgeries can be considered to alleviate seizures and improve quality of life.⁵ 

Developmental delay

Developmental delay refers to a condition in which a child does not reach the typical developmental milestones expected for their age. This can present as a child taking longer than expected to take a first step or say their first word. Epidermal nevus syndrome has been associated with global (meaning in multiple developmental areas) delays in both cognitive and motor skills. The extent of developmental delays. In those with epidermal nevus syndrome varies from patient to patient, with some only being affected with mild intellectual or learning difficulties.⁵ 

Parents and caregivers are encouraged to watch for early signs of developmental delay in children with epidermal nevus syndrome, as early interventions can help with the improvement of quality of life in the future. Such early interventions include services like speech and language therapies or physical therapy. 

Structural brain abnormalities

Differences in the brain structures of those with epidermal nevus syndrome are common and usually cause the observable neurological symptoms outlined above. Imagine studies like MRI or CT scans can reveal abnormalities like:

• Hemimegalencephaly⁴ - A condition in which one half of the brain is enlarged. 
• Cortical dysplasia⁶ - A condition in which a part of the brain called the cerebral cortex does not form correctly. 
• Vascular malformations¹ -  Various malformations in the blood vessels supplying blood to the brain. 

Hydrocephalus and increased intracranial pressure

Hydrocephalus refers to the buildup of cerebrospinal fluid inside the brain. This can be caused by the structural abnormalities present in epidermal nevus syndrome. The buildup of fluid in the brain leads to increased pressure in the head, which comes with its own serious neurological complications if not treated appropriately. 

In infants, symptoms include:

• Rapid head growth 
• Seizures 
• Vomiting
• Irritability
• Developmental delays

Treatment of hydrocephalus depends on factors such as the age of the patient, symptoms and the severity of the condition. The fluid may be drained with surgery or medicine. 

Less common but notable neurological issues

Less commonly observed but still notable neurological issues that can arise due to epidermal nevus syndrome include:¹

• Hemiparesis - The inability or difficulty in moving one side of the body
• Problems with muscle movement - Such as disorganised movement or paralysis
• Problems with vision or the eyes

Diagnosis and monitoring

The diagnosis of epidermal nevus syndrome begins with the recognition of the observable epidermal nevi on the skin. Their location (if on or around the head) may prompt clinicians to further investigate neurological symptoms. This can include observations for seizures or developmental delays or imaging studies to look for any structural changes in the brain. 

Due to its generally widespread effects involving multiple organ systems, epidermal nevus syndrome is usually monitored by a multidisciplinary team. Developmental monitoring allows for early interventions and improved quality of life. 

Treatment and management

Currently, there is no cure for epidermal nevus syndrome; however, many of its symptoms can be managed: 

• Seizures are typically treated with antiepileptic drugs, dietary therapies or surgical procedures. 
• Developmental delays benefit from a holistic approach using therapies like speech therapy, physical therapy and occupational therapy. 
• Education plans may support those with learning difficulties. 
• Hydrocephalus is usually treated with medicines or surgical interventions to relieve pressure on the brain. 

The goal of treatment is not to cure epidermal nevus syndrome but to reduce symptoms, improve function and maximise quality of life. 

Living with epidermal nevus syndrome

Living with epidermal nevus syndrome can often feel overwhelming. Connecting with support networks or advocacy groups can provide encouragement, advice and a sense of community. 

Summary

Epidermal nevus syndrome is a rare but complex condition that goes beyond the skin to include neurological complications like seizures, developmental delays, structural brain abnormalities and a buildup of fluid in the brain (hydrocephalus). Because its effects can vary widely from person to person, early diagnosis and monitoring are essential. There is no current cure for epidermal nevus syndrome; however, the neurological symptoms can be managed with medication, therapies and surgery. With the help of a multidisciplinary care team, early intervention and a strong support network, individuals living with epidermal nevus syndrome can improve their quality of life.