Introduction

Epidermal Nevus Syndrome (ENS) is a rare, congenital condition. It is characterised by the appearance of distinctive skin lesions with developmental abnormalities that affect the skin, nervous system, eyes, skeleton, and occasionally organs.¹

These lesions often show up at birth or within the first year of life. ENS comes from genetic mosaicism,² this is when a gene mutation that happens after fertilisation impacts only some of the body's cells, leading to the patchy distribution of the skin lesions and potentially other developmental differences 

The associated gene mutations include:³

• FGFR3 
• HRAS and KRAS
• PTCH1

These skin abnormalities serve as the first clue to health professionals; however, other non-specific ENS symptoms may also involve seizures, developmental delays, structural brain malformations, eye defects, and skeletal anomalies like spine issues.⁴ 

Skin manifestations

The most common and the earliest signs of Epidermal Nevus Syndrome is the occurrence of epidermal nevi. These are skin lesions in which the skin grows relatively differently, creating patches that may look slightly raised, thickened, or darker than the surrounding skin. The distinctive feature to observe is that they often follow “Blaschko’s lines.” These are natural patterns in the skin laid down by the epidermal cells' pathways during early foetal development in the womb. 

Over time, these skin patches can change in appearance; they can thicken and be a rough texture-wise, or even take on a wart-like appearance. Whilst they are not harmful, they are an important sign to doctors that there could be other features of ENS to look for.⁵

Neurological indicators

There can be varying effects of ENS on the nervous system; especially as a child grows, both parents and physicians can frequently observe developmental difficulties.  For example, some cases have shown that children with ENS start to have seizures, which can vary from short bursts to relatively more intense episodes.⁶ The management of these seizures can be challenging, especially with only conventional medications that do not target the main cause.

Signs of developmental delay, such as slower progress in speaking, walking, or sitting than in comparison to peers, can also be seen in children with ENS.⁷ As the child gets older, there may be learning challenges that become a lot more apparent. Also, it is worth noting that some structural differences can be visualised by neuroimaging, such as MRI scans.⁴ Such differences and delayed developmental progress can negatively impact a child’s quality of life if not given treatment or therapy.

For instance, Hemimegaloencephaly is a condition that can occur when one half of the brain is usually larger than the other; this vast difference in size can cause seizures in children.⁸ Whilst these neurological symptoms can appear, not all children with ENS will experience them as this is not a specific symptom of only ENS. 

Therefore, identifying indicators alongside acknowledging the potential differential diagnoses is very crucial for planning the child's care and treatment. The most efficient interventions that can truly make a difference, like seizure management and developmental support, are only made possible by early recognition.

Eye manifestations

Another sector in which ENS may showcase itself is by affecting the eyes.⁹ Some children have been observed to be born with coloboma, a small gap in one of the structures of the eye that is formed during early fetal development. Whilst some children can also be born with a condition called strabismus.¹⁰ This is when the eyes do not align properly. Over time, these changes can affect how well a child sees, and in some cases, there is a chance that vision loss may affect a child’s overall quality of life. 

What makes this particularly important is that eye problems are not always obvious at first glance. A child may not complain of poor vision, especially when very young, so careful ophthalmologic screening is recommended once initial ENS is suspected. Acknowledging these issues as early as possible allows for the best chance for supportive treatment, whether through glasses, surgery, or other clinical interventions.

Skeletal features

It is worth noting that ENS does not just affect the skin, brain, or eyes, but it can also influence how bones develop. One feature is hemihypertrophy, which is where only one side of the body grows larger than the other.¹¹ For example, a child’s arm or leg on one side may appear longer and thicker in comparison to the other side. This can sometimes create practical challenges with balance, walking, or posture, whilst also impacting a person's mental health.

Other children may also develop scoliosis, a curving of the spine, or a congenital bone deformity that is present from birth.¹² Furthermore, there have been reports of limb length discrepancies, meaning one leg may be shorter than the other. 

Orthopaedic care is a vital part of ENS management, whether that be through physical therapy, braces, or, in some cases, surgery to correct significant differences. This is because although skeletal disorders may vary widely in severity and are patient-specific, all cases are bound to have a significant impact on a child’s mobility and comfort. 

Other systemic involvement

Though less common, ENS can also affect other internal organ systems. Some children get diagnosed with cardiac anomalies present at birth, renal or urogenital malformations, which result in the kidneys, bladder or reproductive organs being affected.¹³ There have been cases in which there have been hormonal imbalances present as well.¹⁴

These issues are much less common than the common skin, brain, or eye symptoms of ENS, but they highlight the fact that this syndrome is truly a multisystem condition. Henceforth, further highlights why children with ENS often benefit from a multidisciplinary team working together to provide complete and comprehensive care.

Summary

Epidermal Nevus Syndrome is a rare condition, and it is incredibly important to recognise its early signs that begin in infancy or early childhood. Although skin lesions are usually the first and most common visible marker, it is also important to consider how ENS can also manifest itself in the nervous system, eyes, skeleton or even internal organs. Early recognition of these signs allows for effective interventions that can improve the quality of life and support the healthy development of children.

ENS can sound daunting and especially scary for children, especially while navigating its complexities. However, it is important to remember that each child’s presentation is unique, and not all children will exhibit every symptom or manifestation described. Ongoing scientific research alongside clinical care continues to improve individuals’ outcomes, and with early support, children with ENS can lead fulfilling lives.