Clinical and Genetic Profile of One Molecularly Confirmed and One Clinically Suspected Case of LZTR1 ‐Related Noonan Syndrome
TL;DR
Two unrelated female pediatric patients evaluated for LZTR1‐related NS following whole‐exome sequencing are reported to 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.
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.