Disease Profile

Hereditary paraganglioma-pheochromocytoma

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of Onset




C74.1 C75.5 D35.0 D35.6


Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease


Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype


X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder


Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other Names (AKA)

Hereditary pheochromocytoma-paraganglioma; Familial pheochromocytoma-paraganglioma; SDHx-related paraganglioma-pheochromocytoma


Blood Diseases; Congenital and Genetic Diseases; Endocrine Diseases;


The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 29072

Hereditary paraganglioma-pheochromocytomas (PGL/PCC) are rare neuroendocrine tumors represented by paragangliomas (occurring in any paraganglia from the skull base to the pelvic floor) and pheochromocytomas (adrenal medullary paragangliomas; see this term).

Hereditary PGL/PCCs represent 30% of all PGL/PCC, for which prevalence is around 1/500,000 for PCC and 1/1,000,000 for PGL.

Clinical description
PGL can be either hypersecreting (catecholamines) or non-secreting and PCCs usually secrete catecholamines. Secreting (sympathetic) PGLs are predominantly found in the thoracic, abdominal and pelvic areas. Hypersecretion manifests as sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, palpitations, pallor and apprehension or anxiety. Urinary bladder PGL may be revealed by painless hematuria and blood pressure increase after micturition. Non-secreting (parasympathetic) PGLs are predominantly located in the head and neck and present as enlarging masses that may be asymptomatic or may be associated with unilateral hearing loss, pulsatile tinnitus, cough, hoarseness of voice, pharyngeal fullness, swallowing difficulty, pain and/or problems with tongue motion. There are no validated markers of malignancy (rate around 15%); the only criterion is the presence of metastases. Gastric stromal tumors and renal cancers are rarely associated.

Up to 10% of genetically determined PCC/PGLs are due to a SDHx germline mutation. Hereditary PCC/PGLs are caused by mutations in the SDHD, SDHC, SDHB, SDHA and SDHAF2 (or SDH5) genes (11q23, 1q21, 1p36.1-p35, 5p15 and 11q31.1 respectively). Transmission is autosomal dominant but associated with maternal genomic imprinting for SDHD and SDHAF2 and expressed when the mutation is inherited from the father. Penetrance depends on the gene, age and tumor sites. Tumors in patients with SDHB mutations are more likely to become malignant than those in patients with other SDHx mutations.

Diagnostic methods
Diagnosis is based on clinical examination and family history. Young age at onset, presence of bilateral, extra-adrenal or multiple tumors, or malignancy suggest an inherited disorder. Imaging studies (MRI, CT) are used to detect tumors and may include functional imaging (scintigraphy, PET). Biochemical testing includes plasma free metanephrines and/or 24 hour-urinary fractionated metanephrines. Molecular genetic testing confirms the diagnosis.

Differential diagnosis
Differential diagnoses include non-hereditary PCC/PGL (although hereditary PCC/PGL tends to present at younger ages, to be multi-focal, bilateral, and recurrent, or to have multiple synchronous neoplasms), PCC/PGL associated with other hereditary conditions (neurofibromatosis type 1, von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, Carney triad and Carney-Stratakis syndrome; see these terms) and familial PCC due to TMEM127 mutation.

Antenatal diagnosis
Prenatal testing is not recommended. Presymptomatic testing is proposed in at-risk children from 6 years of age.

Management and treatment
Treatment for secreting tumors involves blood pressure control with alpha-blockers followed by surgery by specialized teams. If the tumors have not metastasized, surgical resection can be curative. Follow-up is required due to the risk of recurrence and malignancy in particular for SDHB mutationcarriers. For head and neck PGL, external radiotherapy can be proposed. When metastases have occurred, other treatment options including chemotherapy and targeted radiotherapy should be proposed.

The disease may be fatal, but some have lived with malignant PCC/PGL for 20 years or more.

Visit the Orphanet disease page for more resources.


This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Adrenal pheochromocytoma
Extraadrenal pheochromocytoma
30%-79% of people have these symptoms
Cerebral hemorrhage
Bleeding in brain
Chest pain
Inability to produce voice sounds
Elevated urinary dopamine
Elevated urinary epinephrine
Elevated urinary norepinephrine
Episodic abdominal pain
Episodic hyperhidrosis
Sporadic excessive sweating
Episodic paroxysmal anxiety

[ more ]

Glomerular sclerosis
High blood calcium levels
Increased calcium in blood

[ more ]

Hypertensive retinopathy
Missed heart beat
Skipped heart beat

[ more ]

Paraganglioma of head and neck
Paroxysmal vertigo
Positive regitine blocking test
High urine protein levels
Protein in urine

[ more ]

Pulsatile tinnitus
Recurrent paroxysmal headache
Sinus tachycardia
Weight loss
5%-29% of people have these symptoms
Arachnoid hemangiomatosis
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

Cranial nerve compression
Elevated calcitonin
Blood in urine
Panic attack
Renal cell carcinoma
Cancer starting in small tubes in kidneys
Retinal capillary hemangioma
Vocal cord paralysis
Inability to move vocal cords
1%-4% of people have these symptoms
Absent iris


FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Iobenguane I 131(Brand name: Azedra) Manufactured by Progenics Pharmaceuticals, Inc.
    FDA-approved indication: July 2018, iobenguane I 131 (Azedra) was approved for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.
    National Library of Medicine Drug Information Portal


Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn More

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on Hereditary paraganglioma-pheochromocytoma. This website is maintained by the National Library of Medicine.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary paraganglioma-pheochromocytoma. Click on the link to view a sample search on this topic.