We present the case of a 22-year-old woman who was diagnosed in childhood with type IIb VHL, with known multiple retinal angiomas, pancreatic cysts, and spinal and cerebellar hemangioblastomas. She was admitted to our hospital complaining of progressive dyspnea and palpitations. On examination, her blood pressure was 159/119 mm Hg and her pulse was 123 bpm. Physical examination revealed a systolic murmur at the mitral focus with irradiation to the axilla and pulmonary rales. Electrocardiography revealed no remarkable findings, except for sinus tachycardia. Laboratory tests showed an elevated N-terminal pro-brain natriuretic peptide and chest X-ray showed signs of pulmonary interstitial edema. The patient was admitted to the Department of Cardiology with the diagnosis of acute decompensated heart failure. Transthoracic echocardiography showed a dilated left ventricle with severely depressed ejection fraction due to generalized hypokinesia and a mild mitral regurgitation (fig. (fig.1a).1a). During admission, the patient had several episodes of paroxysmal dyspnea despite treatment with β-blockers and diuretics. Due to the clinical suspicion of adrenal gland disease, 24-hour urinary catecholamine and metanephrine tests were requested. Cardiac MRI was performed in order to complete the cardiomyopathy study, and confirmed the echocardiographic findings as well as revealed an incidental finding of a great left renal mass. The 24-hour urine laboratory tests showed markedly elevated levels of norepinephrine, total catecholamines, normetanephrine and metanephrine with normal epinephrine values: 24-hour norepinephrine 468 μg (normal range: 23-105), 24-hour epinephrine 13 μg (normal range: 4-20), 24-hour total catecholamines 658 μg (normal range: 217-575), 24-hour normetanephrine 2,988 μg (normal range: 105-354), 24-hour total metanephrine 3,013 μg (normal range: 0-1,000). Therefore, an abdominal MRI was performed, which showed the presence of two cystic masses (fig. (fig.2)2) located at the left hypochondrium. Surgical resection of both masses was performed (after α-blockade with phenoxybenzamine and β-blockade with propranolol) through a laparoscopic approach, confirming the diagnosis of pheochromocytoma and clear cell renal carcinoma on histology. During follow-up, blood pressure and heart rate values normalized (124/77 mm Hg, 78 bpm), 24-hour urinary catecholamine values returned to normal range (norepinephrine 69 μg/24 h, total catecholamine 221 μg/24 h, normetanephrine 202 μg/24 h and total metanephrine 259 μg/24 h) and the patient had no new episodes of palpitations or dyspnea. Six months after surgical resection, echocardiography was repeated and showed a left ventricle with normal diameters and preserved ejection fraction (fig. (fig.1b).1b). Genetic analysis revealed a germline mutation (exon 3 deletion) of the VHL tumor suppressor gene on the short arm of chromosome 3. As the patient had no family history of VHL, it was concluded that it was a de novo mutation.
PatientID: None
KindredID: 1
Case: F, 22Y0M, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: No family history of VHL, it was concluded that it was a de novo mutation.
CasePresentingHPOs: HP:0009711; HP:0001737; HP:0009713; HP:0006880; HP:0002094; HP:0001962; HP:0011703; HP:0031664; HP:0001635; HP:0002375; HP:0001653; HP:0002666; HP:0006770 (Retinal capillary hemangioma, Pancreatic cysts, Spinal hemangioblastoma, Cerebellar hemangioblastoma, Dyspnea, Palpitations, Sinus tachycardia, Systolic heart murmur, Congestive heart failure, Hypokinesia, Mitral regurgitation, Pheochromocytoma, Clear cell renal cell carcinoma)
CaseHPOFreeText: 22-year-old woman who was diagnosed in childhood with type IIb VHL, with known multiple retinal angiomas, pancreatic cysts, and spinal and cerebellar hemangioblastomas. She was admitted to our hospital complaining of progressive dyspnea and palpitations. Physical examination revealed a systolic murmur at the mitral focus with irradiation to the axilla and pulmonary rales. Electrocardiography revealed no remarkable findings, except for sinus tachycardia. Chest X-ray showed signs of pulmonary interstitial edema. The patient was admitted to the Department of Cardiology with the diagnosis of acute decompensated heart failure. Transthoracic echocardiography showed a dilated left ventricle with severely depressed ejection fraction due to generalized hypokinesia and a mild mitral regurgitation. During admission, the patient had several episodes of paroxysmal dyspnea. Cardiac MRI was performed in order to complete the cardiomyopathy study, and confirmed the echocardiographic findings as well as revealed an incidental finding of a great left renal mass. Abdominal MRI was performed, which showed the presence of two cystic masses located at the left hypochondrium confirming the diagnosis of pheochromocytoma and clear cell renal carcinoma on histology.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: Exon 3 Deletion (c.464-?_642+?del)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: N/A
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: exon_loss_variant
CivicName: Exon 3 Deletion
MultipleGeneVariants: N/A