Noonan Syndrome (PTPN11) Sequencing

Background Information for Noonan Syndrome (PTPN11) Sequencing:
Characteristics of Noonan Syndrome (NS): Short stature, developmental delay, dysmorphic facial features, congenital heart disease, broad or webbed neck, superior pectus carinatum and inferior pectus excavatum, low set nipples, cryptorchidism, coagulation and lymphatic disorders.
Characteristics of LEOPARD syndrome: Lentigines, ECG abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness.
Incidence: 1 in 1000 to 1 in 2500 for NS; rare for LEOPARD syndrome.
Inheritance: Autosomal dominant.
Penetrance: Unknown.
Cause of NS: Deleterious mutations in PTPN11, SOS1, RAF1, KRAS and other unidentified genes.
Cause of LEOPARD syndrome: Mutations in PTPN11 exons 7 and 12 as well as other unidentified genes.
Gene tested: PTPN11.
Clinical Sensitivity: 50 percent of NS is due to PTPN11 mutations; unknown for LEOPARD syndrome.
Methodology: Bidirectional sequencing of the entire PTPN11 coding region and intron-exon boundaries.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations and large deletions/duplications will not be detected. Mutations in genes, other than PTPN11, will not be detected. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.