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  2. www.scielo.br www.scielo.br
    Molecular analysis of the Von Hippel-Lindau (VHL) gene in a family with non-syndromic pheochromocytoma: the importance of genetic testing
    1
    1. ClingenBaseline 24 Oct 2026
      One year later, a 10-year-old sister of the proband (II-2) was referred to our service because of palpitations, weight loss, diaphoresis, and shooting pain attacks that had started about two weeks earlier. Based on this clinical picture and because of her family history, a pheochromocytoma was suspected immediately. Her urinary metanephrines were elevated to 12.2 mg/g creatinine (< 1 mg/g). A CT of the abdomen revealed a mass in the left adrenal; there were no lesions in the pancreas or the kidney. This mass was also positive on MIBG scintigraphy. As in her brother, there was no suggestion that the paraganglia would also be involved. Her MRI of the brain, and her echocardiogram were both normal. She was then treated with an alpha-blocker (prazosin) in preparation for an open adrenalectomy. Histology and immunohistochemistry confirmed diagnosis of a pheochromocytoma in the left adrenal gland.

      PatientID: II-2

      KindredID: 1

      Case: F, 10Y0M, Ethnicity Unknown

      DiseaseAssertion: Adrenal pheochromoyctoma

      FamilyInfo: The patient’s brother (II-1) was found to harbor the same germline mutation the patient harbored and had bilateral adrenal pheochromocytoma at 14Y. The same germline missense mutation was detected in another sister (II-4) with right adrenal pheochromocytoma and her asymptomatic daughter (III-1). The father was not available for genetic testing because he had died, apparently secondary to a hypertensive crisis. The five other family members which underwent genetic testing did not have the mutation.

      CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

      CaseHPOFreeText: At 10Y, the patient reported palpitations, weight loss, diaphoresis, and shooting pain attacks. Her urinary metanephrines were elevated to 12.2 mg/g creatinine. A CT of the abdomen revealed a mass in the left adrenal gland. Histology and immunohistochemistry confirmed diagnosis of left adrenal pheochromocytoma. Additional screening revealed no other tumours, so this fit the criteria of VHL type 2C.

      CaseNotHPOs: HP:0002668; HP:0012090; HP:0012210 (Paraganglioma, abnormal pancreas morphology, abnormal renal morphology)

      CaseNotHPOFreeText: There were no lesions in the pancreas or the kidney, there was also no suggestion that the paraganglia would also be involved. Her MRI of the brain, and her echocardiogram were both normal.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F(c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma AgeOfPresentation:adrenalpheochromocytoma:10 Mutation:Germline RefSeq:N/A AssumedRefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) FamilyPedigree Familial AminoAcidChange:VALtoPHE ClinVarID:2224 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    scielo.br/j/abem/a/MbLMTLsfq6jvN3HLJt5qZHH/
  3. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Two Childhood Pheochromocytoma Cases due to von Hippel-Lindau Disease, One Associated with Pancreatic Neuroendocrine Tumor: A Very Rare Manifestation
    1
    1. ClingenBaseline 24 Oct 2026
      Case 2This 10 year old girl presented with intermittent fever for the past one month. Her birth history was unremarkable. She was the fourth child of nonconsanguineous parents. Her family history was not significant for tumor occurrence. Physical examination revealed a blood pressure level of 160/100 mmHg (95p: 120/79 mmHg) and a heart rate of 110 beats per minute. Laboratory tests showed an elevated 24 h urinary VMA level of 83 mg/day. Abdominal MRI revealed a 44x33 mm, well circumscribed mass with a necrotic core in the left adrenal gland. Subtotal adrenalectomy was performed and histologic examination showed that the tumor was PCC. During two years of follow-up, a 20x19x12 mm mass was detected in the right adrenal gland on abdominal MRI. PET-computed tomography (CT) with 68Ga-DOTA‐DPhe1, Tyr3‐octreotate (68Ga- DOTATATE) showed increased uptake in the right adrenal gland and a 11x10 mm nodular lesion in the corpus of the pancreas (Figure 2). The tumoral masses in the adrenal gland and pancreas were removed. Histologic investigation of adrenal and pancreas specimens confirmed the diagnosis of PCC and PNET (World Health Organisation grade 3) respectively. One year later, an 8x7 mm lesion in the pancreas, compatible with recurrence, was observed on abdominal MRI and confirmed with 68 Ga-DOTATATE PET-CT. Splenectomy and subtotal pancreatectomy were performed for removal of the lesion. Histologic examination of the pancreatic lesion reported a neuroendocrine tumor. Bilateral PCC with PNET suggested the diagnosis of VHL disease. Molecular genetic analysis of the VHL gene revealed a heterozygous missense mutation c. 386 T>G (p.Leu129Pro) which has been previously described. No additional VHL tumor developed during three years follow up.

      PatientID: 2

      KindredID: 2

      Case: F, 13Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Family history was not significant for tumor occurrence.

      CohortInfo: Two cases of VHL disease in children, who presented with PCC as the first manifestation.

      CasePresentingHPOs: HP:0006748, HP:0030405 (Adrenal pheochromocytoma, pancreatic endocrine tumour)

      CaseHPOFreeText: At age 10, abdominal MRI revealed a 44x33 mm mass with a necrotic core in the left adrenal gland. Subtotal adrenalectomy was performed and histologic examination showed that the tumor was PCC. During two years of follow-up, a 20x19x12 mm mass was detected in the right adrenal gland and a 11x10 mm nodular lesion in the corpus of the pancreas which was found to be a pancreatic endocrine tumour. One year later, the pancreatic endocrine tumour reoccured.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.L129P (c.386T>C) *the cDNA change is misrecorded in the paper as 386T>G

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 625242 https://www.ncbi.nlm.nih.gov/clinvar/variation/625242/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: L129P (c.386T>C)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:VHL NonFamilial DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:pancreaticendocrinetumor AgeOfPresentation:adrenalpheochromocytoma:10 AgeOfPresentation:adrenalpheochromocytoma:12 AgeOfPresentation:pancreaticendocrinetumor:13 AgeOfPresentation:pancreaticendocrinetumor:12 cDNAposition:386 ProteinPosition:129 AminoAcidChange:LEUtoPRO ClinVarID:625242 MutationType:missense_variant;transition CivicName:L129P(c.386T>C) AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:5542 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5985389/