Pheochromocytoma/paraganglioma syndrome-1 (PPGL1) is an autosomal dominant disorder characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas arise from chromaffin cells in the adrenal medulla, whereas paragangliomas arise in extra-adrenal sympathetic ganglia in the thorax, abdomen, and pelvis or from parasympathetic paraganglia in the head and neck area (summary by Cascon et al., 2023). Paragangliomas, also referred to as 'glomus body tumors,' are tumors derived from paraganglia located throughout the body. Nonchromaffin types primarily serve as chemoreceptors (hence, the tumor name 'chemodectomas') and are located in the head and neck region (i.e., carotid body, jugular, vagal, and tympanic regions), whereas chromaffin types have endocrine activity, conventionally referred to as 'pheochromocytomas,' and are usually located below the head and neck (i.e., adrenal medulla and pre- and paravertebral thoracoabdominal regions). PPGL can manifest as nonchromaffin head and neck tumors only, adrenal and/or extraadrenal pheochromocytomas only, or a combination of the 2 types of tumors (Baysal, 2002; Neumann et al., 2004). The triad of gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal paraganglioma constitutes a syndrome that occurs mainly in young women and is known as the Carney triad (604287). This triad is not to be confused with the other Carney syndrome of myxoma, spotty pigmentation, and endocrinopathy (160980). Baysal (2008) provided a review of the molecular pathogenesis of hereditary paraganglioma. Genetic Heterogeneity of Pheochromocytoma/Paraganglioma Syndrome See also PPGL2 (601650), caused by mutation in the SDHAF2 gene (613019) on chromosome 11q13; PPGL3 (605373), caused by mutation in the SDHC gene (602413) on chromosome 1q21; PPGL4 (115310), caused by mutation in the SDHB gene (185470) on chromosome 1p36; PPGL5 (614165), caused by mutation in the SDHA gene (600857) on chromosome 5p15; PPGL6 (618464), caused by mutation in the SLC25A11 gene (604165) on chromosome 17p13; and PPGL7 (618475), caused by mutation in the DLST gene (126063) on chromosome 14q24.

An extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.

A tumor that develops in the retrostyloid compartment of the parapharyngeal space, arising from an island of paraganglion tissue derived from the neural crest that is located on the vagus nerve.

A middle ear paraganglioma arising from paraganglia around the tympanum. Signs and symptoms include a mass behind the tympanum, tinnitus, and conductive hearing loss.

Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.

A paraganglioma arising from paraganglia in the head and neck. Representative examples include the carotid body and jugulotympanic paragangliomas.

Pheochromocytoma originating from the adrenal medulla.

A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.

A rapid heartrate that exceeds the range of the normal resting heartrate for age.

A paraganglioma (a neuroendocrine neoplasm) originating in a carotid artery.

A type of hypertension associated with pheochromocytoma.

An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.

Pulsatile tinnitus is generally classified a kind of objective tinnitus, meaning that it is not only audible to the patient but also to the examiner on auscultation of the auditory canal and/or of surrounding structures with use of an auscultation tube or stethoscope. Usually, pulsatile tinnitus is heard as a lower pitched thumping or booming, a rougher blowing sound which is coincidental with respiration, or as a clicking, higher pitched rhythmic sensation.

Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.

Recurrent attacks of severe anxiety, which occur without restriction to any particular situation or set of circumstances, are therefore unpredictable.

Repeated episodes of headache with rapid onset, reaching a peak within minutes and of short duration (less than one hour) with pain that is throbbing, pulsating, or bursting in quality.

A term referring to the inability to speak. It may result from injuries to the vocal cords or may be functional (psychogenic).

Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.

A loss of the ability to move the vocal folds.

Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.

An abnormal increase in catecholamine concentration in the blood.