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

Autor: Blanc A; Service de génétique clinique, CHRU de Nancy, Nancy, France., Bonnet C; Laboratoire de génétique médicale, CHRU Nancy, Nancy, France.; Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France., Wandzel M; Laboratoire de génétique médicale, CHRU Nancy, Nancy, France., Roth V; Laboratoire de génétique médicale, CHRU Nancy, Nancy, France., Duffourd Y; Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.; Université de Bourgogne, INSERM UMR_1231 GAD, Dijon, France., Safraou H; Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.; Université de Bourgogne, INSERM UMR_1231 GAD, Dijon, France., Leheup B; Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France., Muller F; Service de Chirurgie orthopédique infantile, CHRU Nancy, Nancy, France., D Colne J; Service d'Ophtalmologie, CHRU Nancy, Nancy, France., Feillet F; Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France.; Centre de Référence des maladies métaboliques, CHRU Nancy, Nancy, France., Schmitt E; Service de Radiologie, CHRU Nancy, Nancy, France., Castro M; Mendelics Genomic Analysis, São Paulo, Brazil.; Medical Genetics Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo HCFMUSP, São Paulo, Brazil., Savatt J; Autism & Developmental Medicine Institute, Danville, Pennsylvania, USA., Burcheri A; Département de Biopathologie - Anatomie et Cytologie Pathologiques, CHRU de Nancy, Nancy, France., Nemos C; Laboratoire de fœtopathologie et de placentologie, CHRU Nancy, Nancy, France.; Département d'histologie, embryologie et cytogénétique de la faculté de médecine, Université de Lorraine, Nancy, France.; Département de Génie Biologique Santé de l'IUT Nancy-Brabois, Université de Lorraine, Nancy, France.; Université de Lorraine Biofonctionnalités et Risques Neurotoxiques (Calbinotox), Nancy, France., Philippe C; Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.; Université de Bourgogne, INSERM UMR_1231 GAD, Dijon, France., Lambert L; Service de génétique clinique, CHRU de Nancy, Nancy, France.; Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Sep; Vol. 194 (9), pp. e63642. Date of Electronic Publication: 2024 May 06.
DOI: 10.1002/ajmg.a.63642
Abstrakt: 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.
(© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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