CSEMO1 - Identification of a Germline ROCK2 Likely Pathogenic Variant in a Rare Case of Adult Pheochromocytoma Following Infantile Adrenal Neuroblastoma

Abstract:

Introduction: Neuroblastoma and pheochromocytoma (PHEO) both originate from neural crest cells but have rarely been reported in the same patient.

Case Presentation: A 31 yo pregnant female presented with new episodes of palpitations, tremors and hypertension (180/90 mmHg). Past medical history included a left adrenalectomy for neuroblastoma at 7 months old, followed by chemotherapy. Hypertension peaks complicated delivery by caesarean section. A PHEO was suspected postpartum, with elevated plasma metanephrines and 24h urinary catecholamines. Adrenal CT-scan showed a 2.0 x 2.5 cm right adrenal mass with high uptake at DOTATATE-PET CT. After alpha-blockers initiation, she underwent a right adrenalectomy at 6 weeks post-partum, without complications. Pathology confirmed a PHEO.
Genetic analysis: A germline multigene panel (PREVENTION GENETICS) revealed no susceptibility variant for PHEOs. Leucocyte and tumoral DNA exome sequencing (Genome Québec) identified a heterozygous splicing variant in ROCK2 (NM_004850.5), exon 4, c.462+1G>A (chr2:11249660), confirmed by Sanger sequencing. RT-PCR demonstrated exon 4 skipping in tumoral DNA. Because exon 4 contains a protein kinase domain, this deletion could lead to dysregulation of ROCK2. Functional studies are ongoing to better characterize the impact of this variant. Although ROCK2 has been linked to neuroblastoma, data is lacking in PHEO. We reviewed exome sequencing results from 70 PHEOs in our database and found no genetic variants in ROCK2.

Conclusion: To our knowledge, we report the first patient with a PHEO and a previous infantile neuroblastoma carrying a germline likely pathogenic ROCK2 variant. This finding may deepen understanding of genetic mechanisms involved in PHEOs development.