Broadening the Okur-Chung syndrome phenotype: adult-onset metabolic features and a contiguous 20p13 deletion in a Turkish multicenter cohort.
TL;DR
This series consolidates Lys198 as a recurrent hotspot across ethnically diverse cohorts, extends the structural-variant spectrum with the first Turkish CSNK2A1 contiguous-gene deletion, and supports adult-onset metabolic-reproductive complications as under-recognized OCNDS features.
Abstract
Okur-Chung neurodevelopmental syndrome (OCNDS; OMIM #617062) is an ultra-rare autosomal dominant disorder caused by heterozygous CSNK2A1 variants encoding CK2α; although the CSNK2A1 Foundation registry lists more than 350 diagnosed individuals worldwide, individual-level phenotypic data have been published for far fewer, and reports from Türkiye remain scarce. We retrospectively studied nine unrelated Turkish probands (4 F/5 M; 11 months to 23 years) from nine medical genetics centers across four geographic regions of Türkiye, diagnosed by exome sequencing (ES; n = 8) or chromosomal microarray (n = 1). A PRISMA 2020-compliant systematic review (inception-April 2026) provided an individual-level comparator pooled with our cohort (n = 61). Six distinct CSNK2A1 alterations were identified: the recurrent p.(Lys198Arg) p + 1 loop hotspot in 4/9 probands (44.4%); novel/rare p.(Arg195Gln) and p.(Asp156His) missense changes; two nonsense variants (p.(Tyr182Ter), p.(Arg333Ter)); and one ~537 kb heterozygous 20p13 contiguous deletion (arr[GRCh37] 20p13(61568_598427)x1). This proband also represents 20p13 deletion syndrome; previously reported cases of that entity were compared with our cohort. Core OCNDS features (developmental delay, intellectual disability, hypotonia, dysmorphism, behavioral disturbance) occurred at frequencies comparable to those in the pooled literature. Adult-onset obesity with type 2 diabetes (2/9) and hypogonadism (2/9), both essentially unreported in the predominantly pediatric pooled literature, were observed in two adolescent/young-adult males (one with p.(Lys198Arg), one with the 20p13 deletion). This series consolidates Lys198 as a recurrent hotspot across ethnically diverse cohorts, extends the structural-variant spectrum with the first Turkish CSNK2A1 contiguous-gene deletion, and supports adult-onset metabolic-reproductive complications as under-recognized OCNDS features. Systematic adolescent and adult metabolic-endocrine surveillance is recommended regardless of variant class.