Endocrine Abstracts

Introduction: Noonan syndrome (NS) is an autosomal dominant disorder or may occur on a sporadic basis, characterized by short stature, typical face dysmorphology and congenital heart defects. NS is a clinical diagnosis. Establishing the diagnosis can be very difficult, especially in adulthood. There is a great variability in expression and the phenotype become less pronounced with increasing age. The scoring system of Van der Burgt et al. has been devised to help the diagnostic process. In 50% of the patients with NS, a missense mutation is found in the PTPN11 gene on chromosome 12. The incidence is reported to be between 1/1000–1/2500 live births.

Subjects: Case 1: A 54-year-old male was studied in the endocrine practice because of subclinical hypothyroidism. He had medical history of mental retardation, bilateral cryptorchidism, hearing loss, cataract and myeloproliferative disorder. Face dysmorphology, pectus excavatum and other characteristic features confirm clinical diagnosis of NS. Karyiotype and molecular study of fragile X premutation were normal. Mutational screening was carried out by direct sequencing of all coding exons of the genes PTPN11, SOS1 and RAF1 and we did not detected heterozygous point mutations or polymorphisms.

Case 2: Fourty-one-year-old woman was refereed for clinical hypothyroidism monitoring. Pulmonary stenosis intervention was performed at the age of eight. Physical examination showed pectus carinatum and face dysmorphology suggesting NS. Clinical diagnosis was confirmed by the finding of pArg552Gly heterozygous mutation in SOS1 gene.

Conclusions: Although NS diagnosis is usually performed in the first childhood, diagnosis in the adulthood should be also suspected because of the implication in genetic advice. NS is genetically heterogeneous and only 50–60% of patients show mutations in the involved genes.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.