A Rare Heterozygous LZTR1 Mutation in an Infant with Noonan Syndrome Running Title: LZTR1 Variant in Noonan Syndrome

Abstract

Background: Noonan syndrome (NS) is a genetically heterogeneous disorder, with several causative variants identified. Up to date, novel leucine zipper-like transcriptional regulator-1 (LZTR1) variants have been reported in a few cases with Noonan syndrome. Case Report: We report the case of a male infant with the phenotypic characteristics of Noonan syndrome, unusual ocular findings, and a LZTR1 variant. Our patient was born prematurely, with antenatal diagnosis of non-immune hydrops, and unremarkable amniocentesis for known Noonan variations. He had dysmorphic features (low set ears, wide nasal bridge, undescended testes), normal weight, and length. After one month of age he developed pulmonary stenosis, and significant extrauterine growth restriction, whereas ocular examination revealed retinal vascular tortuosity. He was discharged at seven months of corrected gestational age, on nocturnal low flow oxygen. Based on van der Burgt's criteria the diagnosis of NS was established. Whole exome sequence analysis revealed a heterozygous variant in the LZTR1 gene (NM_006767.4):c.27delG (p.(Gln10Argfs*15). Conclusion: Given that new LZTR1 mutations may be identified, the evaluation of an extended genetic panel should be applied in suspected NS cases.