Clinical and Genetic Profile of One Molecularly Confirmed and One Clinically Suspected Case of LZTR1-Related Noonan Syndrome.

Abstract

Noonan syndrome (NS) is a clinically heterogeneous condition caused by pathogenic variants in genes of the RAS/MAPK signaling pathway, presenting as a spectrum of phenotypic features rather than a single uniform disorder. We report two unrelated female pediatric patients evaluated for LZTR1-related NS following whole-exome sequencing. The first patient presented with isolated short stature, subtle dysmorphic features, and normal neurodevelopment. The second displayed multisystem involvement including developmental delay, skeletal abnormalities, and auditory processing disorder. A heterozygous pathogenic variant in LZTR1 was confirmed in the first patient, while the second carried a heterozygous LZTR1 variant of uncertain significance, rendering her diagnosis provisional. Neither patient had congenital heart defects. These cases illustrate the marked phenotypic variability of LZTR1-related NS and underscore that, while cardiac defects may be absent in some individuals, appropriate cardiac surveillance remains necessary.