Poster Display Malignancy and PID

GENOTYPE-PHENOTYPE VARIATIONS AND SPECTRUM OF MALIGNANCIES IN PATIENTS WITH NOONAN SYNDROME: A REVIEW OF LITERATURE

Lecture Time
10:03 - 10:04
Presenter
  • Shaimaa S. Eissa, Egypt
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
179
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Noonan syndrome (NS)the commonest RASopathy, autosomal dominant trait, characterized by short stature, craniofacial dysmorphism, congenital heart defects and susceptibility to cancer. A relationship is suggested between the underlying genotype and the apparent phenotype. The aim of this review is to examine NS’s genotype-phenotype variations and the spectrum of malignancies.

Methods

A review of previously published literature through PubMed database. Articles were chosen if they characterized NS, were available in English and were peer reviewed.

Results

Ninety-three articles met the inclusion criteria. NS was described as the commonest of an inherited overlapping group of disorders collectively known as “RASopathies”. Heterozygous mutations in PTPN11, SOS1, KRAS, NRAS, BRAF, SHOC2, CBL, and others were identified as leading etiologies through abnormal activation of the RAS-MAPK signaling that's also incriminated in oncogenesis. Forty-seven articles described abnormal myelopoiesis, particularly Juvenile Myelo-Monocytic Leukemia (JMML) as the commonest malignancies followed by CNS tumors. Solid tumors as neuroblastoma, chondroma and rhabdomyosarcoma were limited to case reports. The clinical features of NS were described in 21 articles and another 7 detailed its genotypic variations. Genotype-phenotype variabilities were described by many authors. Germline CBL mutations had increased risk of neurological disorders, JMML but lower risk for cardiac defects, growth retardation, and cryptorchidism. NRAS positive NS linked to hyperpigmentation. Neurofibromatosis-Noonan (NFNS) harbor both PTPN11 and neurofibromin mutations were described distinctly.

Conclusions

Available research suggests the relationship between the underlying genotype and the variably expressed phenotype in NS.Mutations in the RAS-MAPK pathway that are potential therapeutic targets,drive oncogenesis and should be molecularly identified in every patient.

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