Objective: In this study,we wish to present the case of two siblings whom we have been monitoring for neurodevelopmental delay,who exhibit stereotypical and dyskinetic movements,and in whom a mutation in the NTNG2 gene was identified following genetic testing

Background: This study investigates the neurodevelopmental impact of a rare missense variant in the Ntng2 gene (c.182G>T;p.Cys61Phe) located at the 9q34.13 locus.NTNG2 encodes Netrin-G2, a vertebrate-specific,GPI-anchored synaptic adhesion molecule that is vital for excitatory synapse development and lamina-specific wiring by binding to the postsynaptic receptor NGL2/LRRC4.Biallelic NTNG2 variants have been linked across multiple reports to a recognizable neurodevelopmental spectrum involving global developmental delay, autistic features, and movement stereotypies.

Method: The patients’ records were reviewed retrospectively.

Results: Here,we present the cases of two siblings (a14-year-old girl and a 10-year-old boy) exhibiting Rett-like stereotypies,impaired mental capacity,hypotonia,and treatment-responsive epilepsy.The identified mutation results in the substitution of a highly conserved Cysteine residue (phyloP100: 10.003) for Phenylalanine at position 61.While in-silico predictors (PP3) strongly suggest a pathogenic impact, the variant is currently classified as a Variant of Uncertain Significance.

Conclusion: Consequently,this study utilizes patient-derived organoid models to provide the functional evidence necessary to bridge this diagnostic gap and characterize how this genetic disruption impairs synaptic connectivity and cortical maturation

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ntng2-associated-neurodevelopmental-disorder-a-recognisable-syndrome-with-stereotypies/