Neurocutaneous Syndromes in Children

Sturge Weber Syndrome – NORD (National Organization for Rare Disorders)

Neurocutaneous Syndromes in Children | Johns Hopkins Medicine

TEXTBOOKS

Roach ES, Santos CS. Neurovascular Disorders and Syndromes in Children. In: Pediatric Neurovascular Disease: Surgical, Endovascular and Medical Management, Alexander MJ, Spetzler RF, editors. 2006 Thieme Medical Publishers, New York, NY. pp. 23-34.

Comi AM. Sturge-Weber Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:258.

JOURNAL ARTICLES

Huang L, Couto JA, Pinto A, Alexandrescu S, Madsen JR, Greene AK, Sahin M, Bischoff J. Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge-Weber Syndrome. Pediatr Neurol. 2017 Feb;67:59-63. https://www.ncbi.nlm.nih.gov/pubmed/27919468

Kaplan EH, Offermann EA, Sievers JW, Comi AM. Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome.Pediatr Neurol. 2017 Jun;71:18-23. https://www.ncbi.nlm.nih.gov/pubmed/28454984

Stafstrom CE, Staedtke V, Comi. Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome. AM.Front Neurol. 2017 Mar 17;8:87. https://www.ncbi.nlm.nih.gov/pubmed/28367137

Comi AM, Sahin M, Hammill A, Kaplan EH, Juhász C, North P, Ball KL, Levin AV, Cohen B, Morris J, Lo W, Roach ES; Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research. 2015 Sturge-Weber Syndrome Research Workshop.Pediatr Neurol. 2016 May;58:12-24. https://www.ncbi.nlm.nih.gov/pubmed/27268758

Kaplan EH, Kossoff EH, Bachur CD, Gholston M, Hahn J, Widlus M, Comi AM. Anticonvulsant Efficacy in Sturge-Weber Syndrome. Pediatr Neurol. 2016 May;58:31-6. https://www.ncbi.nlm.nih.gov/pubmed/26997037

Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368:1971-1979. http://www.ncbi.nlm.nih.gov/pubmed/23656586

Lo W, Marchuk DA, Ball KL, et al. Updates and future horizons on the understanding, diagnosis and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol. 2012;54:214-223. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805257/

Bay MJ, Kossoff EH, Lehmann CU, Zabel TA, Comi AM. Survey of aspirin use in Sturge-Weber syndrome. J Child Neurol. 2011;p26:692-702. http://www.ncbi.nlm.nih.gov/pubmed/21427442

Comi AM. Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome. Neurologist. 2011;17:179-184. http://www.ncbi.nlm.nih.gov/pubmed/21712663

Kossoff EH, Borsage JL, Comi AM. A pilot study of the modified Atkins diet for Sturge-Weber syndrome. Epilepsy Res. 2010;92:240-243. http://www.ncbi.nlm.nih.gov/pubmed/20934305

Miller RS, Ball KL, Comi AM, Germain-Lee EL. Growth hormone deficiency in Sturge-Weber syndrome. Arch Dis Child. 2006;91:340-341. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2065976/

INTERNET

Takeoka M, Riviello JJ Jr. Sturge-Weber Syndrome.Medscape. Updated: May 05, 2017. Available at: http://emedicine.medscape.com/article/1177523-overview Accessed June 19, 2017.

Enjolras O. Sturge-Weber Syndrome. Orphanet Encyclopedia. Last update: March 2014. Available at: http://www.orpha.net/consor/cgi-bin/Disease_Search.

php?lng=EN&data_id=591&Disease_Disease_Search_diseaseGroup=Sturge-Weber-Syndrome-&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Sturge-Weber-syndrome&title=Sturge-Weber-syndrome&search=Disease_Search_Simple Accessed June 19, 2017.

Source: https://rarediseases.org/rare-diseases/sturge-weber-syndrome/

Sturge-Weber syndrome

Neurocutaneous Syndromes in Children | Johns Hopkins Medicine
Alison J Sebold BS (

Ms. Sebold of the Sturge-Weber Syndrome Center at the Kennedy Krieger Institute has no relevant financial relationships to disclose.

)
Anne M Comi MD (Dr. Comi, Director of the Sturge-Weber Syndrome Center at the Kennedy Krieger Institute, has no relevant financial relationships to disclose.)
Michael V Johnston MD, editor. (

Dr. Johnston of Johns Hopkins University School of Medicine has no relevant financial relationships to disclose.

)
Originally released April 13, 1994; last updated July 25, 2018; expires July 25, 2021

This article includes discussion of Sturge-Weber syndrome, encephalotrigeminal angiomatosis, encephalofacial angiomatosis, and Sturge-Weber-Dimitri syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Sturge-Weber syndrome is a neurocutaneous disorder that presents with a facial capillary malformation (port-wine birthmark), abnormal blood vessels on the surface of the brain (leptomeningeal angioma), and glaucoma.

The discovery of the underlying somatic mosaic mutation in GNAQ treatment trials, tissue studies, and the utilization of innovative neuroimaging techniques are leading the way to a new understanding of pathogenesis and potential treatment strategies.

Sturge-Weber patients frequently develop seizures, focal neurologic impairments, visual problems, and cognitive deficits. Early diagnosis is important in providing optimal care for complications.

In this article, the author summarizes research into the pathophysiology of this unique disorder and explains the most current diagnosis and treatment approaches utilized at the Hunter Nelson Sturge-Weber Syndrome Center at the Kennedy Krieger Institute.

Key points

• Diagnosis of Sturge-Weber syndrome brain involvement requires an MRI with contrast.
• Sturge-Weber syndrome (and isolated port-wine birthmarks) are caused by a somatic mutation in the GNAQ gene.
• Prolonged and frequent seizures in infants and young children contribute to neurologic decline.
• Low-dose aspirin has been shown to decrease the frequency and severity of seizures and stroke- episodes in Sturge-Weber syndrome.

Historical note and terminology

Sturge-Weber syndrome documentation began when Schirmer first identified an association between bilateral facial angiomatous nevus and bilateral buphthalmos (eye enlargement) (Schirmer 1860).

In 1879 Sturge described a relationship between facial and ocular angiomatous lesions and cerebral pathology that led to focal seizures, as well as hemiparesis contralateral to the facial angioma (Sturge 1879). Kalischer provided neuropathological confirmation of the cerebral lesions (Kalischer 1897).

In 1922 Weber noted intracranial calcifications (Weber 1922), which were also reported by Dimitri in 1923 (Dimitri 1923).

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Source: https://www.medlink.com/article/sturge-weber_syndrome

Neurocutaneous Syndromes in Children

Neurocutaneous Syndromes in Children | Johns Hopkins Medicine

Neurocutaneous syndrome is a broad term for a group of rare neurological (brain, spine, and peripheral nerve) disorders. These diseases are lifelong conditions that can cause tumors to grow inside the brain, spinal cord, organs, skin, and skeletal bones. The most common disorders found in children are skin lesions.

The three most common types of neurocutaneous syndromes include the following:

  • Tuberous sclerosis (TS)

  • Neurofibromatosis (NF): Type I, Type II, and schwannomatosis

  • Sturge-Weber disease

Tuberous sclerosis, NF, and Sturge-Weber disease are all conditions that are congenital (present at birth).

Although the true prevalence of tuberous sclerosis is not known, it is estimated that this disease occurs in one in 6,000 persons in the U.S. It is an autosomal dominant condition. Autosomal means that both males and females are equally affected and dominant means that only one copy of the gene is necessary to have the disorder.

 Many children born with TS are the first cases in a family, since the majority of TS is caused by a new gene change (mutation), and is not inherited. However, parents of a child with TS may have very subtle symptoms of the disorder, and should be carefully examined.

Even if no symptoms are present, the parents are considered at a slightly increased risk to have another child with TS, greater than that of the general population.

According to the National Institute of Neurological Disorders and Stroke (NINDS), fibromatosis Type 1 (NF1) occurs in about one in 3,000 to 4,000 births in the U.S.

NF1 is an autosomal dominant condition caused by a gene on chromosome 17, which is inherited from a parent with the disease (in half of the cases).

Neurofibromatosis Type 2 (NF2) occurs less frequently, affecting about one in 25,000 births in the U.S. The gene which causes NF2 is found on chromosome 22.

A parent with NF has a 50/50 chance of having a child with the disease. 

NF may also be the result of a new gene change (mutation). Thirty to 50 percent of NF cases are caused by a new mutation and not inherited. Males and females are equally affected, regardless of how the disease occurs. Schwannomatosis is a recently-recognized form of NF that is genetically distinct from NF1 and NF2. It occurs rarely, and only 15 percent of cases are the inherited form.

The cause of Sturge-Weber disease is unknown, and is considered to be sporadic (occurs by chance). Sometimes, other family members will have hemangiomas (a benign growth that consists of blood vessels) to a lesser degree than the person with Sturge-Weber disease.

The child may have varying degrees of symptoms associated with each condition. The following are the most common symptoms of tuberous sclerosis, neurofibromatosis, and Sturge-Weber disease. Symptoms may include:

  • Tuberous sclerosis. Growths, called tubers, are often found growing inside of the brain and retinal area of the eye.

    Tuberous sclerosis affects many organs in the body including the brain, spinal cord, lungs, heart, kidneys, skin, and skeletal bones in the child.

    Intellectual disability, developmental delays, seizures, and learning disabilities are also associated with this disease.

  • Neurofibromatosis (NF). There are three distinct types of NF, classified as NF I, NF II, and schwannomatosis:

    • Neurofibromatosis I. This is the more common of the two disorders. It is also called Von Recklinghausen's disease. The classic symptom of NF I is light brown patches of pigment on the skin, called cafe-au-lait spots. Benign (non-cancerous) skin tumors associated with this condition are called neurofibromas.

      Neurofibromas are often found growing on the nerves and in various organs of the child's body. There is a high rate of brain tumors in patients associated with NF. Less than one percent of individuals with NF will have malignant (cancerous) changes in the neurofibromas.

      Lisch nodules, which are small tumors on the iris (colored part of the eye), may appear around adolescence, but usually do not cause problems. Hearing loss, headaches, seizures, scoliosis, and facial pain or numbness may also be present.

      Intellectual disability is present in up to one percent of individuals with neurofibromatosis I, while other children may have learning problems and hyperactivity.

    • Neurofibromatosis II. According to the NINDS, this type of neurofibromatosis affects approximately one in 25,000 people, and symptoms are usually noticed between 18 and 22 years of age. It is known as bilateral acoustic neurofibromatosis and is less common.

      This disease is characterized by tumors on the eighth cranial nerve, which can lead to hearing loss, headaches, problems with facial movements, problems with balance, and difficulty walking. Hearing loss may be noted as early as the teenage years.

      Other clinical signs of NF II may include seizures, neurofibromas (skin nodules), and cafe-au-lait spots (although these are not nearly as common as in NF I).  

    • Schwannomatosis. The primary feature that distinguishes schwannomatosis from NF1 and NF2 is the growth of multiple schwannomas throughout the body except the vestibular nerve is not involved.

      Extremely intense pain is the main symptom, which occurs when a schwannoma becomes larger or presses on a nerve or nearby tissue.

      Other symptoms that may be experienced include numbness, tingling, or weakness in the fingers and the toes.

  • Sturge-Weber disease. The classic symptom of this disease is a port wine stain located on the child's face, typically near or around the eye and forehead areas.

    A port wine stain is present from birth and is a flat area on the child that varies in color from red to dark purple. The birthmark is caused by the formation of too many tiny blood vessels under the skin.

    There may also be associated brain abnormalities on the same side of the brain as the face lesion. Neurological changes that occur with this condition may include seizures, muscle weakness, changes in vision, and  intellectual disability.

    Glaucoma (a condition that causes increased pressure in the eye) may also be present at birth. Un tuberous sclerosis and NF, Sturge-Weber disease does not affect the other organs of the body.

The symptoms of neurocutaneous syndromes may resemble other conditions. Always consult your child's doctor for a diagnosis.

Tuberous sclerosis, NF, and Sturge-Weber disease are congenital (present at birth). The diagnosis is made with a physical examination and diagnostic tests.

During the examination, the doctor obtains a complete prenatal and birth history of the child and asks if other family members are known to have any of these conditions.

In older babies and children, the doctor will also ask about developmental milestones, since these disorders can be associated with other neurological problems and may require further medical follow-up.

Diagnostic tests may include:

  • Blood tests

  • Genetic testing. Diagnostic tests that evaluate for conditions that have a tendency to run in families.

  • X-ray. A diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.

  • Magnetic resonance imaging (MRI). A diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

  • Computed tomography scan (also called a CT or CAT scan). A diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce horizontal, or axial, images (often called slices) of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general X-rays.

  • Electroencephalogram (EEG). A procedure that records the brain's continuous, electrical activity by means of electrodes attached to the scalp.

  • Eye examination

  • Tissue sample of the tumor or skin lesion

Specific treatment for neurocutaneous syndromes will be determined by your child's doctor :

  • Your child's age, overall health, and medical history

  • The extent of the condition

  • The type of condition

  • Your child's tolerance for specific medications, procedures, or therapies

  • Expectations for the course of the condition

  • Your opinion or preference

Since neurocutaneous syndromes are lifelong conditions that are not curable, the focus is on medically managing the symptoms. A child is best treated with an interdisciplinary team that may include the following healthcare providers:

  • Pediatrician/family practitioner

  • Neurologist. A doctor who specializes in conditions of the brain, nerves, and spinal cord.

  • Neurosurgeon. A surgeon who specializes in operating on the brain and spinal cord.

  • Orthopaedic surgeon. A surgeon who specializes in conditions of the muscles, tendons, ligaments, and bone.

  • Ophthalmologist. A doctor who specializes in conditions of the eye.

  • Nurse

  • Rehabilitation team (physical, occupational, speech therapy, audiology)

Surgery may be needed to remove tumors that may be cancerous, as well as for cosmetic reasons.

Since tuberous sclerosis, NF, and Sturge-Weber disease are lifelong conditions that are not correctable, management includes focusing on preventing or minimizing deformities and maximizing the child's capabilities at home and in the community. Positive reinforcement will encourage the child to strengthen his or her self-esteem and promote independence.

The full extent of the disease is usually not completely understood immediately after birth, but may be revealed as the child grows and develops.

Genetic counseling may be recommended by the doctor to provide information on the recurrence risks for these disorders and any available testing.

Source: https://www.chop.edu/conditions-diseases/neurocutaneous-syndromes-children