Diencephalic syndrome (ORPHA:1672)
Diencephalic syndrome (DS) is a rare condition characterized by profound emaciation and failure to thrive (with normal caloric intake and normal linear growth), hyperalertness, hyperkinesia and euphoria, in the presence of hypothalamic tumors.
Epidemiology
The prevalence is unknown.
Clinical description
DS usually presents in infants or young children (mean age 6 months), but can also occur rarely in older children and adults. DS usually occurs in the presence of low grade astrocytoma/glioma brain tumors of the hypothalamus, which may extend into the optic pathway. These tumors are usually more aggressive and appear at a younger age when associated with DS. Rarely, DS can be secondary to craniopharyngioma, as well as other suprasellar tumors. Manifestations of DS include weight loss, eventually leading to severe emaciation (despite normal caloric intake and linear growth) with an absence of subcutaneous fat, as well as hyperalertness, hyperkinesia, and cheerfulness extending to euphoria in some. Nystagmus, strabismus, decreased visual acuity (and very rarely blindness), optic pallor, hydrocephalus, headache, somnolence, and vomiting have also been reported in some cases. Hypothalamic obesity may occur due to hypothalamic damage. Normal or precocious intellectual development is noted. Rarely, tumors may also be associated with neurofibromatosis type 1.
Etiology
A variety of chiasmatic and hypothalamic low-grade gliomas have been reported to be associated with DS, most commonly pilocytic and pilomyxoid astrocytoma, but there are case reports of craniopharyngioma, suprasellar ependymoma, suprasellar germinoma, suprasellar epidermoid cyst, and hypothalamic spongioblastoma. These tumors may lead to hypothalamic dysfunction and/or degeneration of the optic nerve. The pathogenesis of DS is unknown. Recently, it was proposed that leptin may be dysregulated, but further studies are needed.
Diagnostic methods
When DS is suspected clinically (failure to thrive in children despite normal caloric intake), gadolinium-enhanced magnetic resonance imaging of the cranium, as well as of the spine (due to frequent leptomeningeal seeding) is performed, and cerebrospinal fluid analysis may also be necessary. Ophthalmologic examination should be performed to check for any visual abnormalities. Growth hormone and ghrelin levels are increased and insulin and leptin levels are decreased, but those changes may be secondary to the patient's body mass index.
Differential diagnosis
The differential diagnosis includes gastrointestinal disorders that lead to severe weight loss such celiac disease.
Management and treatment
Treatment aims at removing or reducing the size of the tumor, by surgical or non-surgical methods. Since complete resection of the tumor is not possible due to its location, tumor resection is usually partial and is generally followed by chemotherapy. Radiotherapy is not commonly used, as the patients are young. Patients also require nutritional supplementation (orally or via nasogastric feeding tube or gastrostomy) for malnutrition while symptomatic. Follow-up after completion of treatment includes regular life-long oncologic, neurologic, ophthalmologic and clinical assessments as precocious puberty and pituitary hormone deficiencies may develop.
Prognosis
Prognosis depends on the histological type and grade of tumor but is poorer in patients with DS than in patients with similar tumors who do not present with DS. Frequently, these tumors continue to progress despite treatment. If untreated, patients have an average survival time of less than 12 months after diagnosis, but with proper treatment the long-term survival is greatly improved.

                            Last update: 
                            October 2015


                            - Expert reviewer(s): 
                            Dr Laurie E. COHEN