Abstract: Noonan syndrome (NS; OMIM#163950) is a relatively common autosomal dominant disorder with a worldwide prevalence of approximately 1:1,000 to 1:2,500. The syndrome is characterized by distinctive facial features, congenital heart defects (CHD), and short stature. Distinctive facial features consist of a broad and high forehead, hypertelorism, downslanting palpebral fissures, a high arched palate, low set and posteriorly rotated ears with a thick helix, and a short neck with excess nuchal skin and low posterior hairline. Additional relatively frequent features include chest deformities, cryptorchidism in males, mild intellectual disability, and bleeding diathesis.1,2 In 2001, missense mutations in the PTPN11 gene were reported in about 50% of NS cases. This gene encodes the tyrosine protein phosphatase nonreceptor SHP2, which is involved in ERK activation via RAS-MAPK pathway.3 Later, several other genes involved in the RAS-MAPK pathway were found to be mutated in NS individuals without PTPN11 mutations, including KRAS, SOS1, RAF1, NRAS, BRAF, MAP2K1, and RIT1, as well as mutations in SHOC2 and CBL causing an NS-like disorder (Noonan syndrome-like disorder with loose anagen hair/ NSLH and Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia/NSLL, respectively).2,4,5The involvement of two other genes,A2ML1 and RRAS is still unclear. Despite the relatively high frequency of NS in the general population, no Indonesian patients havebeen reported. Here, we report the first Indonesian case with a confirmed molecular diagnosis of NS.
Author: Iffa Mutmainah, Willy Nillesen, Farmaditya Mundhofir, Tri Winarni, Ineke van der Burgt, Helger Yntema, Sultana Faradz
Journal Code: jpkedokterangg160027