Mild neurodevelopmental disorder due to reduced SHMT2 enzymatic activity caused by novel compound heterozygous variants: expanding the phenotypic spectrum.

Biallelic variants in SHMT2 cause neurodevelopmental disorders with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB; OMIM: 619121). This recently described metabolic disorder are characterized by severe intellectual disability, microcephaly, spastic paraplegia, peripheral neuropathy, corpus callosum dysgenesis, facial and limb deformities, and progressive hypertrophic cardiomyopathy. Herein we describe the clinical characteristics of a 13 years old patient with novel compound heterozygous SHMT2 missense variants (c.1274G>A: p.R425Q and c.1042C>T: p.R348W), presenting with mild intellectual disability, corpus callosum dysgenesis, and speech delay. Different from previous cases, our patient represents the mildest phenotype reported to date, and expand the phenotypic spectrum of disease associated with SHMT2 variants.
Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board (IRB) of Hunan Provincial Maternal and Child Health Hospital. Written informed consent was obtained from the legal guardians of all participants involved. This consent encompasses all aspects of participation and data usage. To protect the privacy of both patients and control subjects, all personal identifiers have been removed from the research data. Consent for publication: We hereby clarify that written informed consent has been obtained from all participants involved in the study regarding the publication of their personal or clinical details, as well as any identifying images. For minor patients, written informed consent has been obtained from their parents. This consent covers the use of these details and images in this study and in any potential publications in scientific journals. Competing interests: The authors declare no competing interests.
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