PatientID: 1

KindredID: 1

Case: F, 44Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: The patient has a notable family history. Her eldest brother had multiple RCCs in both kidneys, bilateral cerebellar hemangioblastomas, and pheochromocytoma in his left adrenal gland (see Patient 2). Her daughter also underwent cortex-sparing adrenalectomies for bilateral pheochromocytomas as well as hemangioblastoma resection in her left cerebellum at age of 19 years, although no testing for VHL was stated.

CasePresentingHPOs: HP:0006748, HP:0030405, HP:0006880, HP:0000107, HP:0005584 (adrenal pheochromocytomas, pancreatic endocrine tumour, cerebellar hemangioblastoma, renal cyst, renal cell carcinoma)

CaseHPOFreeText: Patient diagnosed at age 29 with bilateral pheochromocytomas when she presented with severe hypertension and two large masses (greater than 6 cm) in her bilateral adrenal glands. At 38 years old, she underwent a resection for a mass found on her pancreas, with pathological analysis of the mass revealing a pancreatic neuroendocrine tumor. At 42 years old, a follow-up CT scan revealed two heterogeneous contrast-enhanced masses, one on the right kidney and one on the left adrenal gland.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S80I (c.239G>T)

LegacyVariant: N/A

ClinVar: 625229 https://www.ncbi.nlm.nih.gov/clinvar/variation/625229/

CAiD: CA16621914 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.239G%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: S80I (c.239G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: M, 48Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family history was unremarkable and proband has no children.

CasePresentingHPOs: HP:0006770; HP:0006880; HP:0001737; HP:0001289; HP:0005584 (Clear cell renal cell carcinoma, Cerebellar hemangioblastoma, Pancreatic cysts, Confusion, Renal cell carcinoma)

CaseHPOFreeText: Presented at age 39 with bilateral renal tumors (2 right side, 3 left side). Pathological evaluation revealed clear cell type renal cell carcinoma (fig. 1, B). After 2 years multiple pancreatic cysts were noted. Two years later 6 bilateral renal cell carcinoma lesions developed. Five years later at age 48 years mental confusion developed and brain MRI showed a cerebellar lesion; histological evaluation revealed cerebellar hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: ex. p.C162W (c.486C>G)

LegacyVariant: c.699C>G

CaseProblemVariantFreeText: N/A

ClinVarID: 223227, https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: C162W (c.486C>G)

MultipleGeneVariants: N/A

PatientID: 4

KindredID: 3

Case: M, 45Y0M, Arab

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL disease was described for this patient. Immediate family members were recommended to genetically test for the relevant variant or monitor for VHL-related symptoms.

CasePresentingHPOs: HP:0006880; HP:0009713; HP:0000107; HP:0001737; HP:0000787 (cerebellar hemangioblastoma; spinal hemangioblastoma; renal cyst; pancreatic cysts; nephrolithiasis)

CaseHPOFreeText: At 40Y, Patient 4 was diagnosed with spinal and cerebellar hemangioblastomas, as well as multiple renal and pancreatic cysts. He was diagnosed with VHL disease type 1. At 43Y, renal cysts and stones were discovered. A year later, more spinal hemangioblastomas and renal stones were found. A year later, cerebellar lesions, as well as renal and pancreatic cysts were reported (see table 1).

CaseNotHPOs: HP:0002088; HP:0001392; HP:0005264; HP:0001743 (abnormal lung morphology; abnormality of the liver; abnormality of the gallbladder; abnormality of the spleen)

CaseNotHPOFreeText: No lesions were observed in the lungs, liver, gallbladder, and spleen.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData:  N/A

Variant: p.N90del (c.268_270del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA645524783, https://reg.genome.network/redmine/projects/registry/genboree_registry/by_caid?caid=CA645524783

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: N90del (c.268_270del)

MultipleGeneVariants: N/A