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Recurrent ganglioneuroma in PTPN11 ‐associated Noonan syndrome: A case report and literature review
Author(s) -
MoralesRosado Joel A.,
Singh Herchran,
Olson Rory J.,
Larsen Brandon T.,
Hager Megan M.,
Klee Eric W.,
Dhamija Radhika
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62178
Subject(s) - ptpn11 , noonan syndrome , proband , ganglioneuroma , germline , medicine , germline mutation , expressivity , mutation , protein tyrosine phosphatase , cancer research , pathology , neuroblastoma , biology , genetics , cancer , gene , colorectal cancer , kras , cell culture , receptor
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.

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