2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Case Series Evaluating LZTR1 Variant Within One Family

Pdf Summary

The document discusses a case series evaluating a variant in the LZTR1 gene within one family. LZTR1 is located on chromosome 22 and is associated with Noonan Syndrome (NS) and Schwannomatosis. NS is characterized by short stature, congenital heart defects, developmental delay, and characteristic facial features. The molecular etiology of NS is believed to be the dysregulation of the RAS/MAPK pathway, with 10% of cases attributed to pathogenic variants in LZTR1. Schwannomatosis is characterized by a predisposition to develop multiple schwannomas and occasional meningiomas, with loss of function variants of LZTR1 predisposing individuals to this condition.<br /><br />The authors recommend ophthalmologic evaluations for patients with NS due to LZTR1 mutations, including visual acuity and dilated evaluations, to assess for abnormalities such as retinal degeneration. However, guidelines for managing NS, especially in LZTR1 predisposed cases, are limited. Further functional studies are needed to better understand LZTR1's role in retinal degeneration and NS.<br /><br />The case series focuses on a family in which whole exome sequencing revealed a missense, likely pathogenic variant in the KT4 domain of LZTR1 (c. 743G>A; p.G248E) in the proband, her twin brothers, and her mother. The three children presented with characteristic clinical manifestations of NS such as short stature, congenital heart defects, and developmental delay. The biologic mother also had the variant and presented with hypermobility and retinal degeneration.<br /><br />Overall, the document highlights the need for more research and guidelines regarding the management of NS cases associated with LZTR1 variants. Ophthalmologic evaluations and genetic testing for retinal degeneration are recommended for individuals with NS due to LZTR1 mutations. The rarity and variability of clinical presentations in LZTR1-associated NS make it important to further investigate and understand this condition.

Asset Subtitle

Presenting Author - Elizaveta Makarova, BS; Co-Author - Patricia L. Gordon, MD, FAAP, FACMG; Co-Author - Katie Hartman, MS, LCGC;

Meta Tag

Brain/Nervous System

Cardiac/circulatory disorders

Clinical History

Eye disorders

Co-Author Patricia L. Gordon, MD, FAAP, FACMG

Co-Author Katie Hartman, MS, LCGC

Presenting Author Elizaveta Makarova, BS

Keywords

LZTR1 gene

chromosome 22

Noonan Syndrome

Schwannomatosis

RAS/MAPK pathway

pathogenic variants

ophthalmologic evaluations

retinal degeneration

genetic testing

clinical presentations