Snijders Blok-Campeau syndrome | |
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Other names | SNIBCPS, IDDMSF |
An image displaying 18 individuals who have Snijders Blok-Campeau syndrome | |
Symptoms | Intellectual disability, Macrocephaly, distinctive facial features |
Usual onset | Before birth |
Duration | Life long |
Causes | Mutations in the CHD3 gene |
Frequency | Approximately 60 cases described in scientific literature, with an estimated 150 diagnosed worldwide |
Snijders Blok-Campeau syndrome is a genetic disorder caused by mutations in the CHD3 gene. [1] It is characterized by impaired intellectual development, macrocephaly, dysarthria and apraxia of speech, and certain distinctive facial features. [2]
Snijders Blok-Campeau syndrome is typically a de novo mutation [3] [4] which generally occurs during the early embryonic stages of development or during the formation of the parent's reproductive cells. [2] This allows for prenatal diagnosis. [5]
Snijders Blok-Campeau syndrome almost always comes with both physical and intellectual disabilities. Those with the condition will typically have trouble in the development of speech and language. Around one half typically have some form of macrocephaly, while around one third show signs of autism or similar conditions. [4]
Characteristics | Percentage | Characteristics | Percentage |
---|---|---|---|
Developmental disorder | 100% [3] [6] | Flexible ligamets | 40% [3] |
Speech delay or disorder | 100% [3] [6] | Central nervous system abnormalities | 39% [6] |
Intellectual disability | 95% [6] | Male genital abnormalities | 35% [3] |
Low muscle tone | 92% [6] | Autism or autism-like features | 33% [6] |
Large or prominent forehead | 85% [3] | Neonatal feeding problems | 31% [3] |
Widely spaced eyes | 77% [3] | Strabism | 30% [3] |
Visual abnormalities | 75% [6] | Seizures | 21% [6] |
Thin upper lip | 74% [6] | Congenital heart disease | 21% [6] |
Broad nasal bridge | 71% [6] | Missing teeth | 16% [6] |
Macrocephaly | 58% [3] | Hearing loss | 13% [6] |
Deep set eyes | 54% [6] | Microcephaly | 5% [6] |
The CHD3 gene is required for chromatin remodeling, a process that regulates gene expression. [7] By allowing for the creation of chromatin, the CHD3 gene affects how tightly DNA is packed into chromosomes. A mutation of the CHD3 gene changes the amount of chromatin produced, causing over or underexpression of other genes. [7] [8]
Due to the rarity of the condition, with only approximately 60 cases documented in scientific literature, [7] Snijders Blok-Campeau syndrome was only discovered in 2018 by clinical geneticist Lot Snijders Blok and clinician-scientist Philippe M Campeau. The mutation was first documented in the paper "CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language". [3]
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two hybridized nucleic acid strands, using energy from ATP hydrolysis. There are many helicases, representing the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases.
CHARGE syndrome is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness. These features are no longer used in making a diagnosis of CHARGE syndrome, but the name remains. About two thirds of cases are due to a CHD7 mutation. CHARGE syndrome occurs only in 0.1–1.2 per 10,000 live births; as of 2009, it was the leading cause of congenital deafblindness in the US.
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Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.
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Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.
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Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the CHD3 gene.
Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene.
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Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.
Chromodomain-helicase-DNA-binding protein 1-like (ALC1) is an enzyme that in humans is encoded by the CHD1L gene. It has been implicated in chromatin remodeling and DNA relaxation process required for DNA replication, repair and transcription. The ALC1 comprises ATPase domain and macro domain. On the basis of homology within the ATPase domain, ALC1 belongs to Snf2 family.
Chromodomain-helicase-DNA-binding protein 2 is an enzyme that in humans is encoded by the CHD2 gene.
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Chromodomain helicase DNA-binding (CHD) proteins is a subfamily of ATP-dependent chromatin remodeling complexes (remodelers). All remodelers fall under the umbrella of RNA/DNA helicase superfamily 2. In yeast, CHD complexes are primarily responsible for nucleosome assembly and organization. These complexes play an additional role in multicellular eukaryotes, assisting in chromatin access and nucleosome editing.
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