Clinical and molecular analysis of Noonan syndrome in Indonesia: a case report
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
