A novel CHD3 variant in a patient with central precocious puberty: Expanded phenotype of Snijders Blok‐Campeau syndrome?

Abstract

Snijders Blok‐Campeau syndrome is an autosomal dominant genetic disorder first described in 2018, mostly associated with de novo variants in the CHD3 gene that affects chromatin remodeling. This syndrome is characterized by developmental delay, speech delay, and intellectual disability, but only about 60 affected individuals have been reported to date. We report a de novo likely pathogenic CHD3 variant (c.5609G > A; p. (Arg1870Gln)) in a young female presenting with features of Snijders Blok‐Campeau syndrome including speech delay, autism spectrum disorder, learning difficulties, characteristic facial dysmorphisms, and a feature not previously described in this syndrome, idiopathic central precocious puberty. Her puberty was controlled with monthly injections of a GnRH analogue. Targeted exome sequencing was negative for genes known to be responsible for central precocious puberty. Our case raises the possibility that variants in CHD3 gene may also result in central precocious puberty. Strengthening this association could expand the phenotypic spectrum of the Snijders Blok‐Campeau syndrome and should be included in multigene panels for precocious puberty.

Autism Spectrum Disorder gene prediction using Machine learning model and Human brain Spatiotemporal gene expression Data

“…An another pathogenic variant in CHD3 p.(His886Arg) was reported in a male patient with a syndromic neurodevelopmental and behavioral disorders including ASD 33 . Moreover, de novo CHD3 variant (c.5609G > A; p. (Arg1870Gln) was identi ed in a young female presenting the features of Snijders Blok-Campeau syndrome including Autism Spectrum Disorder and learning di culties, 34 . In addition, our ranking model strongly predicted another ASD candidate genes, GRIK3 (glutamate ionotropic receptor kainate type subunit 3) (score = 0.9), that are the excitatory neurotransmitter receptors in the mammalian brain and are activated in a diversity of normal neurophysiologic processes.…”

Novel genotypes and phenotypes in Snijders Blok-Campeau syndrome caused by CHD3 mutations

“…Three keywords, “Snijders Blok–Campeau syndrome,” “ CHD3 ,” and “SNIBCPS,” were used for the literature search in PubMed. Finally, eight articles were summarized and analyzed ( Coursimault et al, 2021 ; Drivas et al, 2020 ; Fan,2021 ; LeBreton et al, 2022 ; Malinger et al, 2021 ; Mizukami et al, 2021 ; Snijders Blok et al, 2018 ; van der Spek et al, 2022 ).…”

Snijders Blok–Campeau Syndrome: Description of 20 Additional Individuals with Variants in CHD3 and Literature Review

“… ( a ) Schematic representation of the variants found in the CHD3 protein (transcript 1, NM_001005273.3) except for the splicing canonical variant that is shown in ( b ), found in our cohort and in the literature [ 1 , 2 , 3 , 4 , 5 , 6 ]. Most of the variants are found within the ATPase/helicase functional domain.…”

“…Initially, 35 patients were described carrying a de novo pathogenic variant that disrupted the CHD3 gene [ 1 ]. To date, 63 patients have been diagnosed through molecular genetic techniques [ 1 , 2 , 3 , 4 , 5 , 6 ]. These patients had missense, in-frame deletions, nonsense and frameshift pathogenic or likely pathogenic variants.…”

“…Percentage was calculated according to the total number of patients reported in the literature. Patients compiled from[1][2][3][4][5][6] (63 patients) and the 20 patients reported herein.…”