Information on the following diseases can be found in the Related Disorders section of this report:

• Brain Tumor
• Tolosa-Hunt Syndrome
• Hydrocephalus

The diencephalic syndrome is a very rare disorder that usually affects young children. It can usually be recognized by three important features; failure to thrive, extreme thinness, and normal linear growth. Patients usually have a history of normal development and weight gain, followed by either a prolonged period of failure to gain weight or weight loss. The individual may have anorexia or even apparently excessive appetite. Over time, a loss of fat under the skin occurs with an associated emaciated appearance. The child may have a relatively large head, as compared with body weight. Overall development is often slowed, but neurological testing is normal. The eyes are often affected and the infant or child may have crossed eyes (strabismus), unusually rapid movements of the eyes (nystagmus), abnormal swelling of the eyes (papilledema) or vision loss. The child may be unusually sleepy and extremely thin. The child usually behaves in a normal, alert, happy manner that is not in keeping with their physical appearance. Height is normal or even above average but growth hormone plasma level is usually higher than normal.
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Diencephalic syndrome usually results from the development of a brain tumor, often a low-grade glioma of the hypothalamic region or astrocytoma. The tumor may invade the anterior third ventricle of the brain or the optic nerve (chiasm) that causes elevated pressure in the skull.

The cause of the weight loss associated with the tumors is unknown, but may be due to a reduced appetite and/or a high rate of metabolism. Other possibilities are excessive growth hormone secretion, activation of proteins produced by the pituitary gland that break down fat, or the secretion of a yet-to-be defined fat mobilizing compound. There is no known genetic predisposition for diencephalic syndrome.
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Diencephalic syndrome is a very rare disorder that affects males and females in equal numbers. Usually the patient is a young infant or child between the ages of 18 months and 3 years of age but it can also develop in during later childhood or even adulthood. The syndrome occurs worldwide. Childhood brain tumors arise in 2.5-3.5 per 100,000 children per year.
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Some symptoms of the following disorders can be similar to those of diencephalic syndrome. However, the extreme emaciation, which is the most obvious feature of diencephalic syndrome, is not present in many other disorders that have similar symptoms (i.e., brain and eye problems).

Brain tumors are abnormal growths in the brain that can be either cancerous (malignant) or noncancerous (benign). The symptoms of malignant and benign brain tumors can be very similar. Depending upon the type of tumor and where it is located in the brain the tumors can cause swelling and compression in specific areas of the brain, headaches, changes in behavior and swelling of the eyes. (For more information on these disorders, choose "General Brain Tumor" as your search term in the Rare Disease Database.)

Tolosa-Hunt Syndrome is a rare disorder that includes headaches, fever and vision impairment. There may be eye muscle paralysis, swelling, and protrusion of the eye, drooping eyelid, and diminished vision. (For more information on this disorder, choose "Tolosa-Hunt" as your search term in the Rare Disease Database.)

Hydrocephalus is characterized by swelling of the brain. This is caused by the abnormal dilation of the ventricles (cerebral spaces) in the brain and the obstruction of the spinal fluid passages of the central nervous system. Hydrocephalus may occur in conjunction with a brain tumor or for other reasons. (For more information on this disorder, choose "Hydrocephalus" as your search term in the Rare Disease Database.).

Diagnosis
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 prior to the onset of weight loss and lack of clear-cut stomach or intestinal problems is suggestive of the diencephalic syndrome. A complete history and clinical evaluation by a physician who specializes in disorders of the brain and nervous system (neurologist) and imaging tests such as CT scans (computed tomographic scans) or MRI (magnetic resonance imaging scans) may help to confirm the diagnosis.

Treatment
Treatment options are limited. Supplemental feeding alone is usually not helpful because the tumor will continue to grow and cause increasing emaciation. Extensive surgery has been reported to result in temporary tumor control, but total removal of the tumor is usually impossible because of its location and tendency to invade other tissues. The most common form of treatment has been biopsy and partial removal of the tumor followed by radiation therapy. More recently, chemotherapy has been reported to be effective in some children with diencephalic syndrome caused by low-grade gliomas..

Several experimental drugs are being investigated for the treatment of brain tumors that may be associated with diencephalic syndrome. These include Interferon alfa-2b, serratia marcescens extract (polyribosomes), adenosine, borolife (sodium monomercaptoundecahydro-closo-dodecaborate), Liposome encapsulated recombinant Interleukin-2, and recombinant human Interferon Beta.

Biodegradable carmustine (biodel) is a plastic-like (polymer) implant that is being studied for treatment of malignant glioma. Photon therapy is a high beam form of radiation therapy being tested as treatments for brain tumors. More studies are needed to determine the long-term safety and effectiveness of these procedures for the treatment of diencephalic syndrome.

Packer RJ. Diencephalic Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:528-529.

Danoff BF, Kramer S, Thompson. The radiotherapeutic management of optic gliomas of children. Int J Radiat Oncol Biol Phys 1980;6:45-50.

Gropman AL, Packer RJ, Nicholson HS, et al. Treatment of diencephalic syndrome with chemotherapy. Cancer 1998;83:166-172.

Markesbery WR, McDonald JV. Diencephalic syndrome. A long-term survival. Am J Dis Child 1973;125:123-125.

Menzes AH, Bell WE, Perret GC. Hypothalmic tumors in children: their diagnosis and management. Child Brain 1977;3:265-280.

Scott EW, Mickle JP. Pediatric diencephalic gliomas: a review of 18 cases. Pediatr Neurosci 1987;13:225-232.

Meissner I, et al. The paramedian diencephalic syndrome: a dynamic phenomenon. Stroke 1987;18(2):380-385.