What are the other Names for this Condition? (Also known as/Synonyms)

• NCM (Neurocutaneous Melanocytosis)
• Neurocutaneous Melanosis
• Neurocutaneous Melanosis Syndrome

What is Neurocutaneous Melanocytosis? (Definition/Background Information)

• Neurocutaneous Melanocytosis (NCM) is a rare, non-heritable condition, characterized by an abnormal proliferation of melanocytes in both the skin and brain
• Melanocytes are cells that produce melanin. These cells are located predominantly in the skin, but can also be found in the eyes, inner ears, heart, bones, and meninges (membrane covering the brain and spinal cord)
• The cause of Neurocutaneous Melanocytosis is not fully-understood. However, there is some evidence to suggest that sporadic mutation(s) during prenatal development may lead to this condition
• Most individuals with Neurocutaneous Melanocytosis may have one giant melanocytic nevi (a large pigmented birthmark) present at birth, while others may have many smaller lesions. The other symptoms of NCM may include increased intracranial pressure, headaches, seizures, decreased alertness, and numbness/tingling sensation on the face
• Neurocutaneous Melanocytosis may be suspected, if a large pigmented birthmark or several small ones are present at birth. The lesion tissue may be biopsied to check for any malignancy. NCM is generally confirmed following an MRI evaluation
• If symptoms are present, surgery and medications may be required to treat them. The prognosis of Neurocutaneous Melanocytosis is typically good in asymptomatic individuals. If there is a malignant development due to the condition, the outcome may be poor

Who gets Neurocutaneous Melanocytosis? (Age and Sex Distribution)

• Neurocutaneous Melanocytosis usually affects children within the first two years of life. It can often be present at birth. Approximately, 30-50% of children born with the disorder may develop symptoms
• The condition is rare and occurs at a frequency between 1:50,000 and 1:200,000
• NCM can occur in both males and females; however, males have a much greater risk for the condition
• All racial and ethnic groups may be affected

What are the Risk Factors for Neurocutaneous Melanocytosis? (Predisposing Factors)

• A major risk factor that contributes to Neurocutaneous Melanocytosis formation is the presence of congenital melanocytic nevi, which is a large pigmented birthmark in the head and neck region

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Neurocutaneous Melanocytosis? (Etiology)

• The exact cause of development of Neurocutaneous Melanocytosis is not completely known. But, it is related to an improper development of the neural crest prior to birth
• The neural crest is an embryonic structure that eventually forms the melanoblasts in skin, most components of the peripheral nervous system, bones of the skull, connective tissue, and the cartilage

Additionally, sporadic mutation(s) in the NRAS gene have been implicated in the development of NCM.

What are the Signs and Symptoms of Neurocutaneous Melanocytosis?

Individuals with Neurocutaneous Melanocytosis may be asymptomatic, or present with signs and symptoms such as:

• A large pigmented birthmark and/or many small pigmented birthmarks
• Abnormal growth of hair on the body (hirsutism)
• Spinal cord compression leading to the following:
  • Muscle weakness
  • Movement disorders and imbalance
  • Reduced sensitivity to touch
• Increased intracranial pressure that can result in:
  • Headaches
  • Blurred vision
  • Vomiting
  • Lack of alertness
  • Seizures
• Intellectual disability

How is Neurocutaneous Melanocytosis Diagnosed?

The diagnosis of Neurocutaneous Melanocytosis is made on the basis of the following tests and exams:

• Complete physical examination with detailed medical history evaluation
• Examination of large or multiple congenital nevi (pigmented birthmarks), by a pediatric dermatologist
• Biopsy of tissue from the nevus (mole): A tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed), and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies, to assist in the diagnosis
• Magnetic resonance imaging (MRI) scan of the central nervous system within the first 4 to 6 months of life, for the evaluation of melanocytic deposits in the thoracic vertebrae and confirmation of NCM

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Neurocutaneous Melanocytosis?

The potential complications from Neurocutaneous Melanocytosis include:

• An increased risk for developing melanoma (a form of malignancy)
• Hydrocephalus, or excess of spinal fluid in the brain
• Seizures
• Problems with movement
• Intellectual disability

Association of Dandy-Walker malformation complex that is seen in some cases can further complicate the condition.

How is Neurocutaneous Melanocytosis Treated?

In general, the treatment of Neurocutaneous Melanocytosis depends upon a variety of factors, including:

• Number of pigmented birthmarks (congenital melanocytic nevi)
• Size of such birthmarks
• Whether symptoms are present

Alleviation of symptoms of Neurocutaneous Melanocytosis is the most common method of treatment. This may be accomplished by the following measures:

• Insertion of a shunt to drain excess fluid from the brain (to treat hydrocephalus), to another location in the body
• Anti-convulsant medications for the management of seizures
• Surgical excision of brain tissue (damaged or abnormal), when the child does not respond to medications
• Surgical removal of congenital melanocytic nevi, to reduce the risk for cutaneous malignant melanoma
• Generally, proper follow-up care with regular screening and check-ups are important and encouraged

Currently, chemotherapy and radiotherapy have generally proven to be ineffective in treating Neurocutaneous Melanocytosis. There have been little effects on the symptoms present and no effect on the survival of the individual.

How can Neurocutaneous Melanocytosis be Prevented?

Currently, Neurocutaneous Melanocytosis is a condition without any preventive methods, as it is the result of a genetic mutation prior to birth. However, the following factors may help reduce the risk for the condition:

• Removal of any birthmarks that are diagnosed as congenital melanocytic nevi will help the symptoms from getting worse
• Regular medical screening at periodic intervals with MRI scans and physical examinations are mandatory. This is necessary due to the rapid onset of the condition, in addition to the risk for melanoma development. Active vigilance is necessary in the first few years of life, if certain symptoms are present in the child

High-risk individuals should consider a multidisciplinary approach, including both regular neurodevelopmental assessments and skin examinations.

What is the Prognosis of Neurocutaneous Melanocytosis? (Outcomes/Resolutions)

• The prognosis of Neurocutaneous Melanocytosis is good and a normal life span is expected, when no symptoms are observed in children with large or several small pigmented birthmarks
• However, the outcome is generally poor, if neurological symptoms such as seizures and hydrocephaly occur. A child may succumb to NCM due to complications from hydrocephalus
• Also, a development of melanocytoma or melanoma of the central nervous system is often fatal

Additional and Relevant Useful Information for Neurocutaneous Melanocytosis:

• The first description of Neurocutaneous Melanocytosis was recorded by Rokitansky in 1861; the condition was named in 1948 by Van Bogaert
• If a condition known as Dandy-Walker malformation complex co-exists with NCM (which occurs in approximately 10% of the cases), the life expectancy of the affected child may be further reduced