PTPN11 – Costello Syndrome

Extensive genetic analyses have excluded PTPN11 as a causative gene in Costello syndrome. In a cohort of 27 unrelated individuals clinically diagnosed with Costello syndrome, no pathogenic PTPN11 variants were identified by denaturing high-performance liquid chromatography or sequencing, including analysis of exons and splice sites (PMID:12752577). This large‐scale case series supports the absence of segregating or de novo PTPN11 mutations in Costello syndrome.

Functional and experimental studies have not demonstrated any role for SHP-2 (the PTPN11 protein product) in the pathogenesis of Costello syndrome. Reports of PTPN11 variants in related RASopathies underscore phenotypic overlap but not genetic causation in Costello syndrome. Consequently, PTPN11 is not included in Costello syndrome–specific diagnostic panels, and targeted testing should focus on HRAS and other established genes.

References

• Clinical genetics • 2003 • Exclusion of PTPN11 mutations in Costello syndrome: further evidence for distinct genetic etiologies for Noonan, cardio-facio-cutaneous and Costello syndromes. PMID:12752577

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