Incomplete Phenotype of Autosomal Dominant Spastic Paraplegia with Intellectual Disability, Nystagmus, and Obesity (SINO Syndrome) Associated with Pathogenic Variant in the KIDINS220 Gene: Case Study

Background . Hereditary spastic paraplegia (HSP) is clinically and genetically heterogeneous group of neurodegenerative diseases. More than 90 forms of NSP with autosomal dominant, autosomal recessive, X-linked and mitochondrial inheritance have been described. One of the recently described autosomal dominant forms is spastic paraplegia with intellectual disability, nystagmus, and obesity (SINO syndrome; OMIM #617296) associated with heterozygous variants in the KIDINS220 gene. There are no cases of this disease described in Russian population. Case description . Sporadic case of SINO syndrome in 3.5-year-old female patient is presented. The diagnosis was confirmed by molecular genetic testing: novel pathogenic variant chr2:8730980T>TC (p.5055dupG; p.Asn1686fs) in the KIDINS220 gene was revealed in heterozygous state. The specific feature of this case was incomplete manifestation of syndrome typical phenotype and presence of various comorbid symptoms. Along with spastic paraplegia manifestations and high anthropometric indicators there was corpus callosum lipoma, premature thelarche, dorsal fistula, however, intellectual disability, nystagmus and obesity were absent. Conclusion . The described case confirms recent data on the association of pathogenic variants in the KIDINS220 gene with neurodevelopmental disorders and extraneural manifestations determined by the encoded protein role in neuronal differentiation and various signaling pathways. Analysis of SINO syndrome clinical picture expands our understanding of disease phenotype.