NORD is very grateful to Roger J. Packer, MD, Children's National Medical Center, Senior Vice President, Center for Neuroscience and Behavioral Medicine; Director, Brain Tumor Institute; Director, Daniel and Jennifer Gilbert Neurofibromatosis Institute; Principal Investigator, Center for Neuroscience Research, for assistance in the preparation of this report.
Synonyms of Diencephalic Syndrome
- Diencephalic Syndrome of Childhood
- Diencephalic Syndrome of Emaciation
- Paramedian Diencephalic Syndrome
- Russell's Diencephalic Cachexia
- Russell's Syndrome
- No subdivisions found.
Diencephalic syndrome is a rare disorder caused by a tumor that is usually located in the diencephalon, a portion of the brain just above the brainstem. The diencephalon includes the hypothalamus and the thalamus. Affected infants and young children may develop symptoms that include the failure to gain weight and grow as would be expected based upon age and gender (failure to thrive) and abnormal progressive thinness and weakness (emaciation). Affected infants and children may behave in an alert, happy and outgoing manner, which is in contrast to their outward appearance. Additional symptoms such as vomiting, vision abnormalities, headaches, and pallor can also develop. Diencephalic syndrome can progress to cause severe, life-threatening complications. Diencephalic syndrome is treated by surgery, radiation, and/or chemotherapy. The reason for the development of the tumor that causes diencephalic syndrome is unknown. Diencephalic syndrome was first described in the medical literature in 1951 by Dr. Russell.
The specific symptoms and severity of diencephalic syndrome can vary from one person to another. The disorder can potentially cause severe, even life-threatening complications. Onset is usually in infancy or early childhood. Usually, there is a period of normal development and weight gain, followed by a prolonged period of failure to gain weight and weight loss.
The most striking feature of diencephalic syndrome is profound emaciation including a uniform loss of body fat (adipose tissue). Emaciation occurs despite normal or near normal caloric intake. Emaciation may progressively worsen. Because of the loss of body fat, affected children may appear muscular. Although weight is affected, length (linear growth) may be normal. Emaciation and failure to thrive may occur following an initial period of normal growth.
Although overall development is slowed, neurological testing is normal. Affected children are usually mentally alert. Some children are overactive and restlessness (hyperkinesia), happy and outgoing, which is not in keeping with their outward appearance. Some affected children are described as intensely excited or happy (euphoric).
Rapid, involuntary, “jerky” movements of the eyes (nystagmus) can be seen in children with diencephalic syndrome. Nystagmus is a notable feature of this disorder, but does not occur in every case. Additional nonspecific symptoms include pallor, vomiting (emesis), and headaches. Degeneration of the nerve that transmits visual stimuli from the eyes to the brain (optic nerve) may also occur (optic atrophy). Vision loss can potentially occur in some cases.
Some affected infants and children develop hydrocephalus, a condition in which excessive cerebrospinal fluid (CSF) in the skull causes pressure on the brain, resulting in a variety of symptoms including a head that appears large in comparison to the rest of the body, swelling of the optic disk (papilledema).
Less often, additional symptoms have been reported including low blood sugar (hypoglycemia), excessive sweating (hyperhidrosis), and high blood pressure (hypertension). In rare cases, disproportionately large hands and feet have developed.
Diencephalic syndrome is caused by a tumor, most commonly located in the hypothalamus or the optic chiasm. The hypothalamus is a special area in the brain that is divided into several regions that have different functions. The hypothalamus controls the pituitary gland by controlling’s the gland’s release of certain hormones. The hypothalamus also helps regulate basic functions of the body including sleep, hunger, thirst, and body temperature. The optic chiasm is the region where the optic nerves pass through to the brain.
A glioma or astrocytoma is the most common tumor associated with diencephalic syndrome. An astrocytoma is a tumor that arises from the star-shaped cells (astrocytes) that form the supportive tissue of the brain. Other supportive tissue of the brain includes oligodendrocytes and ependymal cells. Collectively, these cells are known as glial cells and the tissue they form is known as glial tissue. Tumors that arise from the glial tissue are collectively referred to as gliomas. Technically, an astrocytoma is a subtype of gliomas, but occasionally the terms are used interchangeably. Astrocytomas that occur in association with diencephalic syndrome tend to be more aggressive and to develop at an earlier age than other astrocytomas arising in the same area. A juvenile pilocytic astrocytoma is the most common cause of diencephalic syndrome. NORD has a report on this tumor. For more information choose “juvenile pilocytic astrocytoma” as your search term in the Rare Disease Database.
Gliomas in the hypothalamus or optic chiasm can sometimes be associated with neurofibromatosis type 1, a rare genetic disorder characterized by the development of multiple noncancerous (benign) tumors of the skin and nerves (neurofibromas). The development of a tumor in the hypothalamus and optic chiasm in neurofibromatosis type 1 and the subsequent development of diencephalic syndrome is not common, but does occur. For more information choose “neurofibromatosis” as your search term in the Rare Disease Database.
In some cases, the causative tumor is unclassified. In extremely rare cases, a different type of tumor such as a ependymoma, dysgerminoma, or ganglioma has been associated with diencephalic syndrome.
The exact underlying manner in which these tumors cause the symptoms of diencephalic syndrome is not fully understood.
Diencephalic syndrome is an extremely rare disorder that affects both males and females. The incidence and prevalence of this disorder in the general population is unknown. The disorder is most often seen in infants or young children, but has also been reported in older children and adults.
Symptoms of the following disorders can be similar to those of diencephalic syndrome. Comparisons may be useful for a differential diagnosis.
Brain tumors are abnormal growths in the brain that can be either cancerous (malignant) or noncancerous (benign). There are many different types of brain tumors. The classification of brain tumors is based on the cells that the tumor originated from and the likelihood that it will spread to other tissues. The symptoms of brain tumors can be very similar. Depending upon the type of tumor and where it is located in the brain, a tumor can cause swelling and compression of nearby structures resulting in various symptoms. (For more information, choose the specific tumor name as your search term in the Rare Disease Database.)
The diagnosis of diencephalic syndrome is suspected in a child who has failed to thrive despite eating an apparently normal diet. A history of relatively normal development followed by a period of weight loss and lack of clear-cut stomach or intestinal problems is suggestive of diencephalic syndrome. A detailed patient history, a thorough clinical evaluation and a variety of specialized imaging techniques are used to establish a diagnosis.
Clinical Testing and Workup
Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues such as brain tissue.
Examination of cerebrospinal fluid can show elevated levels of certain proteins as well as the presence of abnormal cells.
The treatment of diencephalic 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, surgeons, neurologists, oncologists, radiation oncologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size and specific location; specific tumor type; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient 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. Psychosocial support for the entire family is essential as well.
There is no agreed upon consensus for the best treatment for individuals with diencephalic syndrome and there are no standardized treatment protocols or guidelines. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with diencephalic syndrome.
Surgery, radiation, and chemotherapy alone or in various combinations have been used to treat this diencephalic syndrome. In some cases, physicians may recommend surgical excision and removal of as much as the tumor as possible (resection). However, because of the area of the brain that is usually affected, surgical removal of the entire tumor is often not possible. Additionally, surgery, even to remove only a portion of the tumor, carries risks due to the tumor’s location deep within the brain.
Radiation therapy can be used to directly destroy cancer cells or to destroy cancer cells left over after surgery. However, the potential for serious side effects exists. Radiation therapy is especially avoided in children less than 5 years of age because of the potential for serious side effects.
Chemotherapy, the use of one or more anti-cancer drugs, has also been used to treat individuals with diencephalic syndrome, particularly those with low grade gliomas. Chemotherapy may be used instead of radiation in very young children to avoid damage to the developing brain. Chemotherapy may also be administered after radiation in an attempt to destroy any cells that remain or may be given during the course of radiation treatment. The type of chemotherapeutic drug therapy used is determined by a neuro-oncologist who examines the grade of tumor, previous treatment, and current health status of the affected individual. Chemotherapeutic drugs that have been used for diencephalic syndrome include carboplatin, carboplatin-vincristine, carboplatin-vincristine-temador, low dose cisplatin-etoposide, and other drug regimens. Recently, molecularly targeted therapies (biologic therapy) have become available for treatment of low-grade pediatric gliomas. Bevacizumab, which targets vascular endothelial growth factor, has been successfully used for some patients with diencephalic gliomas. Also, agents interfering with RAS-MAPK signaling hold great promise for treatment of diencephalic tumors.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, in the main, contact:
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Organizations related to Diencephalic Syndrome
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Brodsky MC. Russell Diencephalic Syndrome of Infancy. In: Pediatric Neuro-Ophthalmology,2nd ed. Springer. New York, NY. 2010:412-413.
Packer RJ. Diencephalic Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:528-529.
Crawford JR, Shayan K, Levy ML. Delayed presentation of diencephalic syndrome associated with leptomeningeal dissemination in a child. BMJ Case Rep. 2013; doi:10.1136/bcr-2013-010265. http://www.ncbi.nlm.nih.gov/pubmed/23774711
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Packer RJ, Jakacki R, Horn M, et al. Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Ped Blood and Cancer. 2009;52:791-795. http://www.ncbi.nlm.nih.gov/pubmed/19165892
Pfister S, Janzarik WG, Remke M, et al. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest. 2008;118,1739-1749. http://www.ncbi.nlm.nih.gov/pubmed/18398503
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Gropman AL, Packer RJ, Nicholson HS, et al. Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and long term control. Cancer. 1998;83:166-172. http://www.ncbi.nlm.nih.gov/pubmed/9655307
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