Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.
Document Type
Article
Publication Date
11-2024
Identifier
DOI: 10.1016/j.gim.2024.101219
Abstract
PURPOSE: Spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising 8 with SINO and 4 with an autosomal recessive condition attributed to biallelic KIDINS220 variants.
METHODS: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed the clinical and molecular data of our cohort and previously reported individuals and, based on functional experiments, reached a better understanding of the pathogenesis behind the KIDINS220-related disease.
RESULTS: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. A total of 92% had their diagnosis within 3 years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact, and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted.
CONCLUSION: Our study provides further insights into the clinical spectrum, etiology, and predicted functional impact of KIDINS220 variants.
Journal Title
Genetics in medicine : official journal of the American College of Medical Genetics
Volume
26
Issue
11
First Page
101219
Last Page
101219
MeSH Keywords
Humans; Female; Male; Phenotype; Intellectual Disability; Child; Child, Preschool; Obesity; Cohort Studies; Adolescent; Spastic Paraplegia, Hereditary; Infant; Mutation; Adult; Membrane Proteins; Heterozygote; Nystagmus, Pathologic
Keywords
Intellectual disability; KIDINS220; Obesity; Spastic paraplegia; Ventriculomegaly
Recommended Citation
Alstrup M, Cesca F, Krawczun-Rygmaczewska A, et al. Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases. Genet Med. 2024;26(11):101219. doi:10.1016/j.gim.2024.101219
COinS
