About linear sebaceous nevus sequence

What is linear sebaceous nevus sequence?

Epidermal nevus syndromes (ENSs) are a group of rare complex disorders characterized by the presence of skin lesions known as epidermal nevi associated with additional extra-cutaneous abnormalities, most often affecting the brain, eye and skeletal systems. Epidermal nevi are overgrowths of structures and tissue of the epidermis, the outermost layer of the skin. The different types of epidermal nevi can vary in size, number, location, distribution and appearance. Neurological abnormalities that can be associated with ENSs can include seizures, cognitive impairment, developmental delays and paralysis of one side of the body (hemiparesis). Skeletal abnormalities can include abnormal curvature of the spine, malformation of the hip and abnormalities of the arms and legs (e.g., underdevelopment or absence or overgrowth of limbs). Ocular abnormalities may include cataracts, clouding (opacity) of the cornea or partial absence of tissue of the iris or retina (colobomas). Endocrine abnormalities such as vitamin D-resistant rickets have been associated with Schimmelpenning syndrome. The specific symptoms and severity of ENSs can vary greatly from one person to another. Most ENSs occur randomly for no apparent reason (sporadically), most likely due to a gene mutation that occurs after fertilization (postzygotic mutation) and is present in only some of the cells of the body (mosaic pattern).

The term "epidermal nevus syndrome" has generated significant controversy and confusion in the medical literature. Originally, the term was used to denote a disorder that was actually several different disorders erroneously grouped together. In the recent past, the term was used to denote a specific disorder now known as Schimmelpenning syndrome. However, the term epidermal nevus syndrome could be correctly applied to several different disorders. Therefore, the umbrella term "epidermal nevus syndromes" now represents a group of distinct disorders that have in common the presence of one of the various types of epidermal nevi. However, there is so far no general agreement how to classify the types of this diverse group of disorders, adding to the confusion within the medical literature. These disorders are quite different from one another and are not "variants" of each other as is sometimes mistakenly stated in the medical literature. In the future, as the genetic molecular basis of these disorders is better understood, the classification may change or expand.

Two other terms that have been used to describe ENSs are "organoid nevus syndrome" and "keratinocytic nevus syndrome". However, it is inappropriate to use these terms to denote a single disorder or interchangeably with epidermal nevus syndromes. Organoid nevus syndrome is a general term that could be applied to at least five different types of ENS. Keratinocytic nevus syndrome is a general term that could be applied to four different types of ENS.


What are the symptoms for linear sebaceous nevus sequence?

The specific symptoms and severity of nevus sebaceus syndrome can vary greatly from one person to another. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals or their parents should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

The characteristic skin lesion that affects individuals with nevus sebaceus syndrome is a sebaceous nevus, which is a type of epidermal nevus. The scalp, neck and face are most often affected. The arms, legs and trunk may also be affected. Sebaceous nevi are usually salmon or yellowed colored, hairless, smooth patches. Eventually (usually around puberty) they become more pronounced and may appear scaly, warty or thickened. When the scalp is involved, large Lesions may be present with associated areas of hair loss (alopecia). Sebaceous nevi may be prominent and easily noticeable at birth or be subtle and unrecognized. Sometimes, sebaceous nevi do not become apparent until after puberty when they go through the above mentioned changes. The lesions, apart from their appearance, usually do not cause additional symptoms.

Nevus sebaceous most often occurs as isolated finding and usually is not associated with any abnormalities in other organs. However, when it occurs with additional extra-cutaneous symptoms, the term, nevus sebaceus syndrome, is appropriate. Some researchers have noted that central facial epidermal nevi may be more likely to be associated with malformations of the brain, eyes and cranial bones.

Neurological abnormalities often occur in individuals with nevus sebaceus syndrome including seizures, delays in attaining developmental milestones (developmental delays), intellectual impairment, damage to certain cranial nerves and abnormalities affecting certain structures of the brain. Such abnormalities include one side of the brain being larger than the other (hemimegalencephaly), malformation (dysplasia) of the certain brain vessels, absence (agenesis) of the bundle of nerves that connects the two cerebral hemispheres (corpus callosum), and defects of the folds of the brain including a smooth brain that lacks the distinctive folds (agyria), abnormally small folds (microgyria) and abnormally thickened folds (pachygyria).

Individuals with nevus sebaceus syndrome may also have Dandy-Walker malformation, a rare malformation of the brain that is present at birth (congenital). It is characterized by an abnormally enlarged space at the back of the brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts of the brain (foramina of Magendiand Luschka). Excessive amounts of fluid accumulate around the brain and cause abnormally high pressure within the skull, Swelling of the head (congenital hydrocephalus), and neurological impairment. Motor delays and learning problems may also occur. Dandy-Walker malformation is a form of “obstructive” or “internal noncommunicating hydrocephalus”, meaning that the normal flow of cerebrospinal fluid is blocked resulting in the widening of the ventricles. Dandy-Walker malformation is often associated with partial agenesis of part of the cerebellum known as the cerebellar vermis. 

Ocular abnormalities also occur in nevus sebaceus syndrome including a partial absence of tissue (coloboma) from the colored portion of the eye (iris) or the membrane lining the back of the eyes (retina), clouding (opacity) of the cornea, crossed eyes (strabismus), defects of the optic nerve and scarring degeneration or detachment of the retina. Some individuals may have a benign, yellowish-white, fatty tumor on the outer portion of the eyeball (epibulbarlipodermoid). A sebaceous nevus on the face can potentially involve structures in the eye including the eyelids and the thin, clear membrane that covers the outer surface of the eye (conjunctiva).

Affected individuals may also have skeletal malformations including abnormal curvature of the spine, dislocation of the hip, and deformities of the limbs. Craniofacial defects such as an unusually prominent forehead (frontal bossing), underdeveloped nasal and orbital bones and asymmetry of the skull may also occur. Additional skeletal malformations may include bone cysts, underdevelopment of the pelvis and incomplete formation of certain bony structures including the ankle, foot and bones of the spinal column (vertebrae).

Individuals with nevus sebaceus syndrome may also develop vitamin D-resistant rickets, a condition characterized by bow deformities of the legs, Pain in the legs and progressive softening of the bone structure. In children, growth rates may be slow, ultimately resulting in short stature. Affected individuals may be prone to fractures.

According to the medical literature, sebaceus nevi are associated with an increased risk of developing secondary benign skin tumors such as trichoblastoma or syringocystadenomapapilliferum, whereas malignant secondary tumors (basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma) arising in association with a sebaceous nevus are very rare.

What are the causes for linear sebaceous nevus sequence?

Recent research has identified individuals with nevus sebaceus syndrome have postzygotic mutations of the KRAS and HRAS genes. In addition, HRAS and KRAS mutations have been found in isolated sebaceous nevus (in the absence of associated extracutaneous abnormalities). More research is necessary to further explore the relationship of ras mutations and the complex phenotype seen in some affected patients.

What are the treatments for linear sebaceous nevus sequence?

The treatment of nevus sebaceus syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, pediatric neurologists, dermatologists, orthopedists, orthopedic surgeons, ophthalmologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.

The specific therapeutic procedures and interventions for individuals with nevus sebaceus syndrome will vary, depending upon numerous factors including the specific symptoms present, the extent of the disorder, an individual’s age and overall health, tolerance of certain medications or procedures, personal preference and other factors. Decisions concerning the use of particular therapeutic interventions should be made by physicians and other members of the healthcare team in careful consultation with the patient and/or parents based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.

Surgery may be performed to improve cosmetic appearance of individuals with nevus sebaceus syndrome. In the past, surgery was recommended because of the risk of malignancy. However, now that the risk of malignancy is much less than previously believed, this view is no longer advocated, especially if surgery will be disfiguring. In addition, the surgical excision of a lesion may not always be possible due to the specific location of the nevus.

Additional therapies for nevus sebaceus syndrome depend upon the specific abnormalities present and usually follow standard guidelines. For example, epilepsy may be treated by anti-seizure medications and certain skeletal and ocular malformations may also be treated surgically. In the medical literature, several cases have been reported where neurosurgery has been used to treat individuals with nevus sebaceus syndrome and epilepsy.

Additional therapies that may be used to treat individuals with nevus sebaceus syndrome include remedial education, physical therapy and occupational therapy all of which should be individualized. Genetic counseling may be of benefit for affected individuals and their families.

What are the risk factors for linear sebaceous nevus sequence?

Nevus sebaceus syndrome affects males and females in equal numbers. The exact prevalence and incidence of the disorder in the general population are unknown. Epidermal nevi (as an isolated finding or a part of a syndrome) have been reported to occur in approximately 1 to 3 per 1,000 live births.

Is there a cure/medications for linear sebaceous nevus sequence?

Treatment for linear sebaceous nevus sequence is directed toward the specific symptoms that are apparent in each individual.

  • The doctor may wait unless there are obvious deformities that need to be addressed.
  • Pediatricians, neurologists, dermatologists, and other healthcare professionals may need to plan the treatment systematically and comprehensively.
  • Therapeutic procedures and interventions specific to individuals with nevus sebaceus syndrome may differ, depending upon numerous factors, like symptoms present, the extent of the disorder, an individual's age and overall health, tolerance of certain medications or procedures, personal preference and other factors.
  • Surgery may be performed to improve the cosmetic appearance of individuals with the syndrome.
  • The surgical excision of a lesion may not always be possible due to the specific location of the nevus.
  • Therapies for nevus sebaceus syndrome depends upon the specific abnormalities present and usually follow standard guidelines.
  • The therapies include remedial education, physical, and occupational therapy, all of which should be individualized.


Symptoms
Salmon or yellowed colored, hairless, smooth patches on the scalp, neck, face, arms, legs and trunk,Large lesions may be present with associated areas of hair loss (alopecia),Neurological abnormalities like seizures, delays in attaining developmental milestones (developmental delays), intellectual impairment, damage to certain cranial nerves and abnormalities affecting certain structures of the brain,Skeletal malformations including abnormal curvature of the spine, dislocation of the hip, and deformities of the limbs,Vitamin D-resistant rickets,Prone to fractures
Conditions
Abnormalities outside the skin, which most commonly affect the brain, eyes and bones,Sebaceous nevi,Organoid epidermal nevus
Drugs
Surgery,Therapies like physical therapy and occupational therapy

Video related to linear sebaceous nevus sequence