A novel homozygous frameshift variant in SPTBN4 causes axonal neuropathy with intellectual disability in a consanguineous family

Abstract

Introduction: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519) is an autosomal recessive condition arising from variations in the SPTBN4 gene. This gene codes for βIV-spectrin, a non-erythrocytic member of the β-spectrin family. Homozygous variants in SPTBN4 disrupt the cytoskeletal machinery responsible for localization of ion channels and functioning of axonal domains, leading to neurological dysfunction. Case presentation: Here, we report three siblings with a homozygous frameshift indel c.1799–1800delGC in the SPTBN4, all presenting with severe muscular hypotonia, dysphagia, absent or limited speech, delayed gross motor development, global developmental delay, and intellectual disability. This condition has been associated with numerous secondary features. Conclusion: The phenotype reported in our family contributes to establishing the core symptoms associated with mutations in SPTBN4, with varying levels of developmental delay, intellectual disability, limited speech, and congenital hypotonia.

Keywords

• Neurodevelopmental disorder
• SPTBN4
• Developmental delay
• Frameshift mutation
• Whole exome sequencing