Recurrent ganglioneuroma in PTPN11‐associated Noonan syndrome: A case report and literature review

Abstract

Noonan syndrome (NS) is an autosomal dominant condition with variable expressivity most commonly due to a germline pathogenic variant in PTPN11, which encodes the protein tyrosine phosphatase SHP‐2. Gain‐of‐function variants in PTPN11 are known to promote oncogenic behavior in affected tissues. We report the clinical description of a young adult male presenting with relapsing ganglioneuromas, dysmorphic features, cardiac abnormalities, and multiple lentigines, strongly suspicious for NS. Solid tumor testing identified the recurrent pathogenic c.922G>A (p.Asn308Asp) in PTPN11. Proband and parental blood sampling testing confirmed c.922G>A as a de novo germline alteration. Comprehensive literature review of solid tumors specifically associated to PTPN11, indicates that this is the first documentation of ganglioneuroma and its clinical recurrence after resection in conjunction with a genetically confirmed NS diagnosis. The findings in our patient further extend the list of neuroblastic and neural crest‐derived neoplasms associated with this condition.

Malignant intracerebral nerve sheath tumor in a patient with Noonan syndrome: illustrative case

“…In the case presented here, there is a background of NS, an autosomal dominant condition with a variable phenotype, in which 50% of cases are due to a germline “gain of function” mutation of the PTPN11 gene; this particular gene is responsible for encoding the nonreceptor protein tyrosine phosphatase SHP2, positively controlling the RAS function within the RAS–mitogen-activated protein kinase (MAPK) signaling pathway. 13 , 14 …”

“…In the case presented here, there is a background of NS, an autosomal dominant condition with a variable phenotype, in which 50% of cases are due to a germline "gain of function" mutation of the PTPN11 gene; this particular gene is responsible for encoding the nonreceptor protein tyrosine phosphatase SHP2, positively controlling the RAS function within the RAS-mitogen-activated protein kinase (MAPK) signaling pathway. 13,14 Considering the nature of the RAS-MAPK pathway and its role in oncogenesis, patients with certain mutations (so-called RASopathies), and thereby NS, are at an increased risk of certain cancers. Somatic mutations of PTPN11 have been reported as being present in 35% of persons with juvenile myelomonocytic leukemia, alongside other hematological malignancies and solid organ tumors, such as lung and colon cancer and neuroblastoma.…”