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2023 ACMG Annual Clinical Genetics Meeting Digital ...
A somatic pathogenic variant in
PTPN11
in ...
A somatic pathogenic variant in
PTPN11
in a patient with vascular malformation and hemihypertrophy
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Pdf Summary
The patient in this case is a 13-year-old male with features resembling Klippel-Trenaunay syndrome, congenital capillary malformations, and venolymphatic malformations on both lower extremities. At 8 years old, he had corrective surgery on his left leg due to hemihypertrophy of the right leg. The PTPN11 gene, which encodes the SHP-2 protein involved in the RAS/MAPK signaling cascade, was found to have a somatic pathogenic variant in the affected tissue of this patient. Most germline variants in PTPN11 are associated with Noonan syndrome, but somatic variants have been described in hematologic malignancies and solid tumors. This case highlights the role of mosaic variants in PTPN11 in disorders of somatic mosaicism (DoSM), which include features such as macrocephaly, vascular malformations, hemihypertrophy, and digit anomalies. The patient did not exhibit any features of Noonan syndrome, suggesting that his presentation was consistent with DoSM. In a previous study, a somatic PTPN11 variant was identified in a patient with severe lateralized overgrowth, vascular proliferation, and cerebral astrocytoma, also lacking features of Noonan syndrome. This case provides further evidence of the involvement of somatic variants in PTPN11 in DoSM and emphasizes the importance of examining pathogenic variants in genes implicated in the RAS/MAPK pathway in patients with clinical features of DoSM. Initial sequencing of genes in the PI3K/AKT/mTOR pathway did not identify any clinically reportable variants, but subsequent analysis of genes implicated in RASopathies identified a pathogenic somatic variant in PTPN11.
Asset Subtitle
Presenting Author - Bahareh Mojarad, PhD; Co-Author - Shelbie Fishman, BA; Co-Author - Katherine King, MD; Co-Author - Bryan Sisk, MD; Co-Author - Julie A. Neidich, MD;
Meta Tag
Genetic Testing
Molecular Pathophysiology
NextGen Sequencing
Sequencing
Variant Detection
Co-Author
Shelbie Fishman, BA
Co-Author
Katherine King, MD
Co-Author
Bryan Sisk, MD
Co-Author
Julie A. Neidich, MD
Presenting Author
Bahareh Mojarad, PhD
Keywords
Klippel-Trenaunay syndrome
congenital capillary malformations
venolymphatic malformations
hemihypertrophy
PTPN11 gene
SHP-2 protein
RAS/MAPK signaling cascade
somatic pathogenic variant
Noonan syndrome
disorders of somatic mosaicism (DoSM)
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