This patient's brother (3 years younger) was followed with the similar accelerated screening protocol of biannual visits with alternating US and plasma catecholamines from the age of 5. At 11 years, the brother had a normal abdominal US, but, 6 months after, he was found to have plasma norepinephrine at 51,506 pmol/L, a 36-fold increase compared to the preceding year. MRI revealed a 3.5 cm adrenal mass, which at retroperitoneoscopic surgery required total adrenalectomy for excision. Pathology confirmed a 2.9 cm pheochromocytoma without residual tumor at the margins. This patient is followed since with a second version of an accelerated regimen. The second iteration of an accelerated regimen consists of biannual plasma catecholamines and visits with annual US. The brother is currently well after 2 years and a half of surveillance.
PatientID: N/A (younger son of index case)
KindredID: 1
Case: M, 13Y0M, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: The patient's mother was the index case in this VHL family, as she was diagnosed with bilateral pheochromocytoma at age 23 and underwent bilateral adrenalectomy. Genetic screening of the mother revealed the VHL variant, which prompted screening of family members. DNA sequencing from blood of consenting family members confirmed the presence of the VHL variant in seven family members (three generations from the maternal side) (see figure 1 for familial pedigree). This included the mother (index case), the patient, his brother, maternal grandmother, uncle and two cousins. The brother, who was 3 years older, was asymptomatic until age 7, where an abdominal ultrasound revealed a left adrenal mass. A total adrenalectomy was performed and at age 1 another mouse was found in the right adrenal gland, which was also removed. 6 years later he was asymptomatic. The uncle developed hemangioblastoma, multiple bilateral renal cell carcinomas, bilateral pheochromocytomas, and succumbed to his disease at age 45. The uncle's two daughters both had the mutation. One of which was found to have pheochromocytoma at age 15 due to routine screening. The other 8 year old daughter has not had any manifestations. No phenotype was noted for the grandmother.
CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)
CaseHPOFreeText: Patient presented with an adrenal mass at 11Y0M, which required total adrenalectomy and remains well 2.5 years later.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.V170G (c.509T>G)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: N/A
CAID: CA351756196, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.509T%3EG
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant; tranversion
CivicName: V170G (c.509T>G)
MultipleGeneVariants: N/A