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Paragangliomas 1(PGL1)

MedGen UID:
358258
Concept ID:
C1868633
Disease or Syndrome
Synonyms: Glomus tumor; Glomus tumors familial 1; Paraganglioma - glomus jugulare; PARAGANGLIOMA, CAROTID BODY; Paragangliomas familial 1; PARAGANGLIOMAS, FAMILIAL NONCHROMAFFIN, 1; Paragangliomata; PGL 1; PGL1; SDHD-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): SDHD (11q23.1)
 
OMIM®: 168000

Disease characteristics

Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas. [from GeneReviews]
Authors:
Tobi Else  |  Samantha Greenberg  |  Lauren Fishbein   view full author information

Additional descriptions

From OMIM
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). PGL 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 Paragangliomas See also PGL4 (115310), caused by mutation in the SDHB gene (185470) on chromosome 1p36; PGL3 (605373), caused by mutation in the SDHC gene (602413) on chromosome 1q21; PGL2 (601650), caused by mutation in the SDHAF2 gene (613019) on chromosome 11q13; PGL5 (614165), caused by mutation in the SDHA gene (600857) on chromosome 5p15; PGL6 (618464), caused by mutation in the SLC25A11 gene (604165) on chromosome 17p13; and PGL7 (618475), caused by mutation in the DLST gene (126063) on chromosome 14q24.  http://www.omim.org/entry/168000
From MedlinePlus Genetics
Paragangliomas and pheochromocytomas can occur in individuals with other inherited disorders, such as von Hippel-Lindau syndrome, Carney-Stratakis syndrome, and certain types of multiple endocrine neoplasia. These other disorders feature additional tumor types and have different genetic causes. Some paragangliomas and pheochromocytomas occur in people with no history of the tumors in their families and appear not to be inherited. These cases are designated as sporadic.\n\nResearchers have identified several types of hereditary paraganglioma-pheochromocytoma. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. The other types are very rare. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.\n\nAlthough most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.\n\nMost paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.\n\nPheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.\n\nHereditary paraganglioma-pheochromocytoma is an inherited condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.  https://medlineplus.gov/genetics/condition/hereditary-paraganglioma-pheochromocytoma
From MedlinePlus Genetics
Researchers have identified several types of hereditary paraganglioma-pheochromocytoma. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. The other types are very rare. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.\n\nParagangliomas and pheochromocytomas can occur in individuals with other inherited disorders, such as von Hippel-Lindau syndrome, Carney-Stratakis syndrome, and certain types of multiple endocrine neoplasia. These other disorders feature additional tumor types and have different genetic causes. Some paragangliomas and pheochromocytomas occur in people with no history of the tumors in their families and appear not to be inherited. These cases are designated as sporadic.\n\nAlthough most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.\n\nMost paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.\n\nPheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.\n\nHereditary paraganglioma-pheochromocytoma is an inherited condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.  https://medlineplus.gov/genetics/condition/hereditary-paraganglioma-pheochromocytoma

Clinical features

From HPO
Carotid body paraganglioma
MedGen UID:
2853
Concept ID:
C0007279
Neoplastic Process
A usually benign neoplasm originating in the chemoreceptor tissue of the carotid body, glomus jugulare, glomus tympanicum, aortic bodies, or the female genital tract.
Glomus jugular tumor
MedGen UID:
4905
Concept ID:
C0017671
Neoplastic Process
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
Vagal paraganglioma
MedGen UID:
141635
Concept ID:
C0474819
Neoplastic Process
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.
Extraadrenal pheochromocytoma
MedGen UID:
263453
Concept ID:
C1257877
Neoplastic Process
Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.
Glomus tympanicum paraganglioma
MedGen UID:
356565
Concept ID:
C1866555
Neoplastic Process
Adrenal pheochromocytoma
MedGen UID:
1636437
Concept ID:
C4551683
Neoplastic Process
Pheochromocytoma originating from the adrenal medulla.
Palpitations
MedGen UID:
14579
Concept ID:
C0030252
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Tachycardia
MedGen UID:
21453
Concept ID:
C0039231
Finding
A rapid heartrate that exceeds the range of the normal resting heartrate for age.
Hypertension associated with pheochromocytoma
MedGen UID:
871214
Concept ID:
C4025693
Disease or Syndrome
A type of hypertension associated with pheochromocytoma.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Pulsatile tinnitus
MedGen UID:
148340
Concept ID:
C0751559
Sign or Symptom
Carotid body paraganglioma
MedGen UID:
2853
Concept ID:
C0007279
Neoplastic Process
A usually benign neoplasm originating in the chemoreceptor tissue of the carotid body, glomus jugulare, glomus tympanicum, aortic bodies, or the female genital tract.
Glomus jugular tumor
MedGen UID:
4905
Concept ID:
C0017671
Neoplastic Process
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
Vocal cord paralysis
MedGen UID:
53047
Concept ID:
C0042928
Disease or Syndrome
Paralysis of the muscles of one or both vocal cords. Signs and symptoms include hoarseness, weak voice, dyspnea, and coughing. Affected individuals are at risk for aspiration pneumonia.
Cranial nerve paralysis
MedGen UID:
57717
Concept ID:
C0151311
Disease or Syndrome
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Vagal paraganglioma
MedGen UID:
141635
Concept ID:
C0474819
Neoplastic Process
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.
Extraadrenal pheochromocytoma
MedGen UID:
263453
Concept ID:
C1257877
Neoplastic Process
Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.
Episodic paroxysmal anxiety
MedGen UID:
923185
Concept ID:
C1387805
Mental or Behavioral Dysfunction
Recurrent attacks of severe anxiety, whose occurence is not restricted to any particular situation or set of circumstances and is therefore unpredictable.
Glomus tympanicum paraganglioma
MedGen UID:
356565
Concept ID:
C1866555
Neoplastic Process
Recurrent paroxysmal headache
MedGen UID:
927617
Concept ID:
C4293708
Sign or Symptom
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.
Adrenal pheochromocytoma
MedGen UID:
1636437
Concept ID:
C4551683
Neoplastic Process
Pheochromocytoma originating from the adrenal medulla.
Loss of voice
MedGen UID:
2006
Concept ID:
C0003564
Sign or Symptom
A term referring to the inability to speak. It may result from injuries to the vocal cords or may be functional (psychogenic).
Hoarse voice
MedGen UID:
5602
Concept ID:
C0019825
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Vocal cord paralysis
MedGen UID:
53047
Concept ID:
C0042928
Disease or Syndrome
Paralysis of the muscles of one or both vocal cords. Signs and symptoms include hoarseness, weak voice, dyspnea, and coughing. Affected individuals are at risk for aspiration pneumonia.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Carotid body paraganglioma
MedGen UID:
2853
Concept ID:
C0007279
Neoplastic Process
A usually benign neoplasm originating in the chemoreceptor tissue of the carotid body, glomus jugulare, glomus tympanicum, aortic bodies, or the female genital tract.
Glomus jugular tumor
MedGen UID:
4905
Concept ID:
C0017671
Neoplastic Process
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
Vagal paraganglioma
MedGen UID:
141635
Concept ID:
C0474819
Neoplastic Process
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.
Extraadrenal pheochromocytoma
MedGen UID:
263453
Concept ID:
C1257877
Neoplastic Process
Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.
Glomus tympanicum paraganglioma
MedGen UID:
356565
Concept ID:
C1866555
Neoplastic Process
Elevated circulating catecholamine level
MedGen UID:
871156
Concept ID:
C4025629
Finding
An abnormal increase in catecholamine concentration in the blood.
Adrenal pheochromocytoma
MedGen UID:
1636437
Concept ID:
C4551683
Neoplastic Process
Pheochromocytoma originating from the adrenal medulla.

Professional guidelines

PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee.
Genet Med 2015 Jan;17(1):70-87. Epub 2014 Nov 13 doi: 10.1038/gim.2014.147. PMID: 25394175
ACMG Board of Directors.
Genet Med 2015 Jan;17(1):68-9. Epub 2014 Nov 13 doi: 10.1038/gim.2014.151. PMID: 25356965
Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society.
J Clin Endocrinol Metab 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498. PMID: 24893135
Reaume MN, Graham GE, Tomiak E, Kamel-Reid S, Jewett MA, Bjarnason GA, Blais N, Care M, Drachenberg D, Gedye C, Grant R, Heng DY, Kapoor A, Kollmannsberger C, Lattouf JB, Maher ER, Pause A, Ruether D, Soulieres D, Tanguay S, Turcotte S, Violette PD, Wood L, Basiuk J, Pautler SE; Kidney Cancer Research Network of Canada.
Can Urol Assoc J 2013 Sep-Oct;7(9-10):319-23. doi: 10.5489/cuaj.1496. PMID: 24319509Free PMC Article
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics.
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. PMID: 23788249Free PMC Article
Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K; North American Neuroendocrine Tumor Society (NANETS).
Pancreas 2010 Aug;39(6):775-83. doi: 10.1097/MPA.0b013e3181ebb4f0. PMID: 20664475Free PMC Article
Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K; American Society of Clinical Oncology.
J Clin Oncol 2010 Feb 10;28(5):893-901. Epub 2010 Jan 11 doi: 10.1200/JCO.2009.27.0660. PMID: 20065170
Zon RT, Goss E, Vogel VG, Chlebowski RT, Jatoi I, Robson ME, Wollins DS, Garber JE, Brown P, Kramer BS; American Society of Clinical Oncology.
J Clin Oncol 2009 Feb 20;27(6):986-93. Epub 2008 Dec 15 doi: 10.1200/JCO.2008.16.3691. PMID: 19075281Free PMC Article

External

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

ACMG SF v3.0, 2021

Recent clinical studies

Etiology

Mason EF, Sadow PM, Wagner AJ, Remillard SP, Flood TA, Belanger EC, Hornick JL, Barletta JA
Am J Surg Pathol 2013 Oct;37(10):1612-8. doi: 10.1097/PAS.0b013e318293d83c. PMID: 23797725
Liu DG, Ma XC, Li BM, Zhang JG
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006 Jan;101(1):102-9. Epub 2005 Oct 12 doi: 10.1016/j.tripleo.2005.05.062. PMID: 16360614
Boedeker CC, Neumann HP, Ridder GJ, Maier W, Schipper J
Otolaryngol Head Neck Surg 2005 Mar;132(3):467-70. doi: 10.1016/j.otohns.2004.09.024. PMID: 15746863

Diagnosis

Liu DG, Ma XC, Li BM, Zhang JG
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006 Jan;101(1):102-9. Epub 2005 Oct 12 doi: 10.1016/j.tripleo.2005.05.062. PMID: 16360614
Boedeker CC, Neumann HP, Ridder GJ, Maier W, Schipper J
Otolaryngol Head Neck Surg 2005 Mar;132(3):467-70. doi: 10.1016/j.otohns.2004.09.024. PMID: 15746863
Bostwick DG, Null WE, Holmes D, Weber E, Barchas JD, Bensch KG
N Engl J Med 1987 Dec 3;317(23):1439-43. doi: 10.1056/NEJM198712033172304. PMID: 2891033

Prognosis

Mason EF, Sadow PM, Wagner AJ, Remillard SP, Flood TA, Belanger EC, Hornick JL, Barletta JA
Am J Surg Pathol 2013 Oct;37(10):1612-8. doi: 10.1097/PAS.0b013e318293d83c. PMID: 23797725

Clinical prediction guides

Bostwick DG, Null WE, Holmes D, Weber E, Barchas JD, Bensch KG
N Engl J Med 1987 Dec 3;317(23):1439-43. doi: 10.1056/NEJM198712033172304. PMID: 2891033

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