Clinical Features of Okur-Chung Neurodevelopmental Syndrome: Case Report and Literature Review

Khamirani, Hossein Jafari; Zoghi, Sina; Motealleh, Ali Reza; Dianatpour, Mehdi; Tabei, Seyed Mohammad Bagher; Mohammadi, Sanaz; Dastgheib, Seyed Alireza

doi:10.1159/000522353

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…Sixteen articles reporting 47 OCNDS patients with germline CSNK2A1 pathogenic variants were included in the study (Akahira-Azuma et al, 2018;Belnap et al, 2023;Chiu et al, 2018;Colavito et al, 2018;Duan et al, 2019;Jafari Khamirani et al, 2022;Martinez-Monseny et al, 2020;Murakami et al, 2022;Nakashima et al, 2019;Okur et al, 2016;Owen et al, 2018;Trinh et al, 2017;Wafik et al, 2023;Wu et al, 2020Wu et al, , 2021Xu et al, 2020). Together with the two patients reported in our study, 49 patients were included in the final analysis.…”

Section: Review Of the Genotypephenotype Relationship In Identified C...mentioning

confidence: 99%

“…However, a clear genotypephenotype correlation has not been established. Most variants in OCNDS are missense variants primarily clustered within the functional regions of the CSNK2A1 kinase domain, while less commonly, frameshift variants have been reported as well (Jafari Khamirani et al, 2022;Okur et al, 2016). The molecular mechanisms underlying CSNK2A1 variants remain incompletely elucidated (Wafik et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…CSNK2A1 predominantly consists of a single extensive functional domain (Figure 1a). OCNDS typically presents with developmental delays, mild‐to‐moderate intellectual impairment, hypotonia, feeding challenges, distinctive facial features, speech delay, and may include non‐specific clinical characteristics such as behavioral issues, disrupted sleep patterns, microcephaly, seizures, and short stature in some cases (Jafari Khamirani et al., 2022; Okur et al., 2016). Previously, OCNDS cases were diagnosed as simplex cases due to de novo heterozygous pathogenic variants in CSNK2A1 with unaffected parents (Chiu et al., 2018; Okur et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

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Okur‐Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion

Nan,

Chu,

Zhang

et al. 2024

Molec Gen & Gen Med

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BackgroundOkur‐Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.MethodsWe performed the whole‐exome sequencing for a patient in a Chinese family. The co‐segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real‐time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild‐type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.ResultsWe identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31‐year‐old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense‐mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.ConclusionWe report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype–phenotype correlation of this condition.

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Section: Review Of the Genotypephenotype Relationship In Identified C...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Okur‐Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion

Nan,

Chu,

Zhang

et al. 2024

Molec Gen & Gen Med

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Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur–Chung neurodevelopmental syndrome

Blanc,

Bonnet,

Wandzel

et al. 2024

American J of Med Genetics Pt A

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The autosomal dominant Okur–Chung neurodevelopmental syndrome (OCNDS: OMIM #617062) is a rare neurodevelopmental disorder first described in 2016. Features include developmental delay (DD), intellectual disability (ID), behavioral problems, hypotonia, language deficits, congenital heart abnormalities, and non‐specific dysmorphic facial features. OCNDS is caused by heterozygous pathogenic variants in CSNK2A1 (OMIM *115440; NM_177559.3). To date, 160 patients have been diagnosed worldwide. The number will likely increase due to the growing use of exome sequencing (ES) and genome sequencing (GS). Here, we describe a novel OCNDS patient carrying a CSNK2A1 variant (NM_177559.3:c.140G>A; NP_808227.1:p.Arg47Gln). Phenotypically, he presented with DD, ID, generalized hypotonia, speech delay, short stature, microcephaly, and dysmorphic features such as low‐set ears, hypertelorism, thin upper lip, and a round face. The patient showed several signs not yet described that may extend the phenotypic spectrum of OCNDS. These include prenatal bilateral clubfeet, exotropia, and peg lateral incisors. However, unlike the majority of descriptions, he did not present sleep disturbance, seizures or gait difficulties. A literature review shows phenotypic heterogeneity for OCNDS, whether these patients have the same variant or not. This case report is an opportunity to refine the phenotype of this syndrome and raise the question of the genotype–phenotype correlation.

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Spastic paraplegia 51: phenotypic spectrum related to novel homozygous AP4E1 mutation

Manoochehri

Goodarzi

Tabei

2022

J Genet

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Clinical Features of Okur-Chung Neurodevelopmental Syndrome: Case Report and Literature Review

Cited by 7 publications

References 41 publications

Okur‐Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion

Okur‐Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion

Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur–Chung neurodevelopmental syndrome

Spastic paraplegia 51: phenotypic spectrum related to novel homozygous AP4E1 mutation

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