Neurofibromatosis & associated disorders/syndromes

Discussion in 'General Health & Wellness' started by slowden, May 4, 2004.

  1. slowden

    slowden New Member

    Neurocutaneous Syndromes

    What are neurocutaneous syndromes?

    Neurocutaneous syndrome is a broad term for a group of neurologic (brain, spine, and peripheral nerve) disorders. These diseases are life-long 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 and Type II
    Sturge-Weber disease
    What causes neurocutaneous syndromes?

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

    Tuberous sclerosis (TS) 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. A parent with TS has a 50/50 chance of having a child with TS. 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.

    Neurofibromatosis (NF) 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). 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). Half of NF cases are caused by a new mutation and not inherited. Males and females are equally affected, regardless of how the disease occurs.

    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.

    What are the symptoms of neurocutaneous syndromes?


    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. Mental retardation, developmental delays, seizures, and learning disabilities are also associated with this disease.
    neurofibromatosis (NF)
    There are two distinct types of NF, classified as NF I and NF II.
    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 café-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. Ten to 15 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. Mental retardation is present in 2 to 5 percent of individuals with neurofibromatosis I, while other children may have learning problems and hyperactivity.
    neurofibromatosis II
    This type of neurofibromatosis accounts for 2 to 5 percent of cases. 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 café-au-lait spots (although this is not as common as in NF I).
    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 mental retardation. Glaucoma (a condition that causes increased pressure in the eye) may also be present at birth. Unlike 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 physician for a diagnosis.

    How are neurocutaneous syndromes diagnosed?

    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 physician 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 physician 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.
    computerized 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 cross-sectional images (often called slices), both horizontally and vertically, 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>
    Treatment of neurocutaneous syndromes:

    Specific treatment for neurocutaneous syndromes will be determined by your child’s physician based on:

    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 life-long 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 physician 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 physician 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.

    Life-long considerations for a child with neurocutaneous syndromes:

    Since tuberous sclerosis, NF, and Sturge-Weber disease are life-long 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/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 physician to provide information on the recurrence risks for these disorders and any available testing.


    Neurocutaneous Disorders
    The Neurocutaneous disorders are conditions that envolve both skin and brain producing some type of "birthmark" or skin lesion and neurologic involvement so that seizures, developmental motor or cognitive problems are present. Most are genetically determined and are expressed in the developing neuroectodermal tissue that divides into the skin and nervous system. This explains the connection of both skin and brain involvement as well as the specific location of some (Sturge-Weber, NF-II) of the conditions and the more random distribution of others (NF-I, TS).

    Neurofibromatosis
    Diagnostic Features
    6 or more cafe-au-lait spots
    axillary freckling
    nodular neurofibromata (may not develop until puberty)

    NF-I (85%) chromosome 17
    Associated findings or symptoms
    visual loss due optic nerve fibromata or gliomas
    megalencephaly
    learning disorders
    seizures
    scoliosis from vertebral dysplasia
    Pseudo-arthrosis (distal tibia is most likely location)
    Lisch nodules on the iris

    NF-II : chromosome 22
    Associated findings or symptoms
    bilateral acoustic nerve neuromata with deafness
    facial nerve palsy and ataxia because of location in the cerebellar-pontine angle
    Complications of Neurofibromatosis
    malignant degeneration in 2nd half of 2nd decade of cerebral nodules
    optic nerve fibromas or large nodules on peripheral nerves (neurofibrosarcoma)
    disfigurement and sphenoid wing dysplasia from enlargement of plexiform neuromatas
    segmental hypertrophies, hypertension, pheochromocytoma

    Tuberous Sclerosis
    Clinical findings
    autosomal dominant with 70% as spontaneous mutation
    cafe-au-lait spots
    hypopigmented macules ash leaf spots - may need Wood's lamp [UV light] to see
    Shagreen (chagrin) patch (irregular shaped area of roughen slightly pigmented skin)
    facial angiofibromas (adenoma sebaceum - may not develop until puberty and can be confused with acne)
    subungual fibromas
    retinal hamartomas
    renal angiomyolipomas
    cardiac rhabdomyomata
    polycystic kidneys
    Seizures in 90% with Infantile spasms when seizures develop in infants
    90+% with Learning Disabilities or Mental Retardation
    Neuropathaology
    Cortical tubers
    subependymal glial noduals (candle wax drippings
    Sturge-Weber Syndrome
    Diagnostic Features
    Port wine stain on the Ophthalmic division of the Trigeminal Nerve (V-I)
    cavernous angioma of the leptomeninges (rail road track calcifications)
    choroidal angioma of the eye that can produce glaucoma
    Seizures occur in over 90% of patients which are often refractory to medication needing hemispherectomy or cortical resection for control.

    Hypomelanosis of Ito
    Diagnostic Features
    Autosomal dominant and spontaneous mutation
    linear hypopigmentation usually multiple segments of one or both sides of body
    iris hypopigmentation
    hemi-hypertrophy
    50% with seizures or static encephalopathy or retardation
    Neuronal migration defects in the 15th week of gestation when melanoblasts migrate form the neural crest.

    Von Hipple Landau
    Diagnostic Features
    Retinal and cerebellar hemangioblastomas with occasional involvement of the medulla and spinal cord
    May present with CNS hemorrhage or seizures
    Cyst on the kidneys, pancreas, epididymis
    rare renal cell carcinomas and pheochromocytomas

    Incontinentia Pigmenti
    Diagnostic Features
    X-linked dominant with lethal effect in Males so condition seen only in females
    Cerebral dysgenesis producing developmental retardation and seizures in 30 to 50%
    Skin abnormality develops after delivery and progresses through three stages:
    Stage 1: in the first 2 weeks of life a rash evolves through erythematous macular, to papular vesicular, bullous to pustular lesions in a linear distribution. (May mimic a viral [Herpes like] eruption at presentation).
    Stage 2: over the next 2-3 weeks the lesions become keratotic and dyskeratotic and leave areas of atrophic skin.
    Stage 3: over the several months the atrophic areas become hyper-pigmented
    [This Message was Edited on 05/04/2004]