Table 1.

Syndrome-related personal and self-reported family history and potential evidence of risk management assessed by manual EHR review^a

Gene(s)	Personal history and self-reported family history	Potential evidence of risk managementb
MEN1 [1–3]	• Clinically identified P/LP MEN1 variant • Multiple endocrine neoplasia type 1 • Wermer syndrome • Primary hyperparathyroidism • Parathyroid tumor • Pituitary adenoma • Zollinger-Ellison syndrome • Gastrinoma • Insulinoma • VIPoma • Glucagonoma • Pancreatic islet cell tumor • Well-differentiated endocrine tumors of the gastro-entero-pancreatic (GEP) tract • Carcinoid tumor • Adrenocortical tumor • Dermatologic manifestations       o Facial angiofibroma       o Collagenoma       o Meningiomas       o Ependymomas • Leiomyoma • Lipoma	Appointments • Genetics • Endocrinology • Otolaryngology • Gastroenterology Surveillance Biochemical: • Calcium • PTH, intact • 25-OH vitamin D • Prolactin • Insulin growth factor-1 • Gastrin • Fasting glucose • Insulin • Chromogranin A • Pancreatic polypeptide • Glucagon • Vasoactive intestinal peptide Imaging: • Head/brain MRI • Pituitary (Sella) MRI • Abdominal CT/MRI • Endoscopic ultrasound • Chest CT/MRI
RET [1, 4–6]	• Clinically detected P/LP RET variant • Multiple endocrine neoplasia type 2 • Medullary thyroid cancer • Pheochromocytoma • Parathyroid adenoma • Parathyroid hyperplasia • C-cell hyperplasia • Hirschsprung disease • Cutaneous lichen amyloidosis	Appointments • Genetics • Endocrinology • Otolaryngology Surveillance Biochemical: • Calcitonin • CEA • Calcium • PTH, intact • 25-OH vitamin D • Plasma-free metanephrines • 24-h urine fractionated metanephrines • Plasma-free catecholamines • 24-h urine fractionated catecholamines • Vanillylmandelic acid Imaging: • Thyroid ultrasound • Abdominal MRI/CT Prophylactic surgery • Thyroidectomy
SDHx (SDHAF2, SDHB, SDHC, SDHD) [1, 7–10]	• Clinically identified P/LP SDHx variant • Hereditary paraganglioma-pheochromocytoma syndrome • Paraganglioma • Pheochromocytoma • Gastrointestinal stromal tumor • Renal cell carcinoma	Appointments • Genetics • Otolaryngology • Endocrinology Surveillance Biochemical: • Plasma-free metanephrines • 24-h urine fractionated metanephrines • Plasma-free catecholamines • 24-h urine fractionated catecholamines • Vanillylmandelic acid • Dopamine and/or 3-methyoxytyramine Imaging: • Whole body CT/MRI        ○ Head/neck CT or MRI        ○ Abdomen/pelvis CT or MRI • Renal ultrasound
VHL1 [1, 12, 13, 15–17]	• Clinically identified P/LP VHL variant • Von Hippel-Lindau syndrome • Renal cell carcinoma • Pheochromocytoma • Endolymphatic sac tumor • Hemangioblastoma (brain, spinal, retinal) • Renal cysts • Pancreatic cysts • Pancreatic neuroendocrine tumor • Epididymal and broad ligament cystadenomas	Appointments • Ophthalmology • Audiology • Otolaryngology • Urology • Endocrinology • Genetics Surveillance Biochemical: • Plasma-free metanephrines • 24-h urine fractionated metanephrines • Plasma-free catecholamines • 24-h urine fractionated catecholamines • Vanillylmandelic acid Imaging: • Abdominal ultrasound • Abdominal MRI Exam: • Audiology assessment • Dilated retinal exam

^aReviewers followed a chart review abstraction guide to search the EHR and collect defined fields of interest, including personal and self-reported family history (up to third-degree relatives) of syndrome-related findings and recommended surveillance and risk reduction activities based on the participant’s variant. This table represents an EHR search strategy. As such, synonyms and outdated diagnostic terms are included to ensure the EHR review was complete as possible. ^bThe risk management behavior list extends to activities that could be considered associated with the ETS variant, even if not the current standard of care for individuals with an ETS variant or if only considered in certain clinical scenarios, in an effort to accurately assess whether they may have been any interventions of relevance. This broad list was constructed by reviewing relevant guidelines and the literature [4, 5, 9, 13–20] and sought to recognize variation in practice, longer time since relevant guidelines were released, and a lack of consensus guidelines for all conditions