Table 5.

Disorders to Consider in the Differential Diagnosis of Hereditary Paraganglioma-Pheochromocytoma Syndromes

GeneDisorderMOITypical Clinical Features of Disorder 1
Overlapping w/Hereditary PGL/PCCDistinguishing From Hereditary PGL/PCC
EPAS1 Polycythemia-paraganglioma-somatostatinoma syndrome 1See footnote 2.PGL
  • Mainly in females
  • Polycythemia
  • Somatostatinoma
FH FH tumor predisposition syndrome (hereditary leiomyoma renal cell carcinoma syndrome)ADPCC/PGL are rare.
  • Cutaneous & uterine leiomyomas
  • Other types of renal carcinoma
MEN1 Multiple endocrine neoplasia type 1 ADPCC/PGL are rare.
  • Parathyroid tumors
  • Pituitary tumors
  • Foregut neuroendocrine tumors, incl pancreatic, lung, & duodenal neuroendocrine tumors
  • Adrenocortical adenomas
NF1 Neurofibromatosis 1 AD
  • PCC that secrete epinephrine &/or norepinephrine
  • PGL are rare.
  • Café au lait macules
  • Axillary & inguinal freckling
  • Neurofibromas (cutaneous & plexiform)
  • Long bone dysplasia
  • Optic glioma
RET Multiple endocrine neoplasia type 2 AD
  • PCC that secrete epinephrine/metanephrine &/or norepinephrine/normetanephrine
  • PGL are rare.
MEN2A:
  • Medullary thyroid carcinoma
  • Hyperparathyroidism
MEN2B:
  • Medullary thyroid carcinoma
  • Mucocutaneous neuromas
  • Ganglioneuromatosis
  • Slender body habitus
  • Joint laxity
  • Skeletal malformations
VHL Von Hippel-Lindau disease AD
  • PCC that secrete norepinephrine/normetanephrine
  • PGL are infrequent.
  • Clear cell renal cell carcinoma
  • CNS hemangioblastomas
  • Renal, pancreatic, epididymal, & broad ligament cysts
  • Pancreatic neuroendocrine tumors
  • Endolymphatic sac tumors

AD = autosomal dominant; CNS = central nervous system; MOI = mode of inheritance; PCC = pheochromocytoma; PGL = paraganglioma

1.
2.

To date, the majority of reported individuals with polycythemia-paraganglioma-somatostatinoma syndrome have the disorder as the result of a somatic mosaic pathogenic variant (i.e., a pathogenic variant not inherited from a parent).

From: Hereditary Paraganglioma-Pheochromocytoma Syndromes

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