Severe intellectual disability-progressive spastic diplegia syndrome | |
---|---|
Other names | CTNNB1 syndrome, CTNNB1-related intellectual disability, Intellectual disability, autosomal dominant 19 [1] |
Specialty | Medical genetics, Pediatry |
Causes | Genetic mutation |
Frequency | Rare, only 1 out of 50,000 live births have this condition |
Severe intellectual disability-progressive spastic diplegia syndrome is a rare novel genetic disorder characterized by severe intellectual disabilities, ataxia, craniofacial dysmorphisms, and muscle spasticity. [2] It is a type of autosomal dominant syndromic intellectual disability. [3] [4] [5] [6] [7]
Individuals with this condition typically show severe intellectual disability, motor delays, severe speech delay and difficulties, infancy-onset hypotonia affecting the trunk, progressive hypertonia affecting the distal limbs, severe progressive microcephaly, autistic-like symptoms, aggressive behavior towards others and/or oneself, sleep abnormalities, and mild facial dysmorphisms such as a broad nose, hypoplastic alae nasi, an elongated/flattened philtrum, and a thin upper lip. [8] [9]
Other symptoms include seizures, nearsightedness, farsightedness, strabismus, syringomyelia, ventriculomegaly, corpus callosum hypoplasia, hearing difficulties, and a delay in CNS myelination. [10]
In rarer cases, a child with the condition might be born with polydactyly. [11]
Most symptoms which characterize this condition arise as a result of the profound intellectual disability associated with this condition, these symptoms can cause more complications, such as communication difficulties, poor school performance, etc. [8]
This condition can be diagnosed through physical examination and genetic testing.
This condition is caused by heterozygous mutations in the CTNNB1 gene, located in the short arm of chromosome 3. [12] [13] [14] [4] [15] The condition, although genetic, is typically not inherited, except in rare cases where it is, [16] as it is usually the result of a de novo mutation. [17] Insertions, deletions, and other types of mutations have been reported. [18]
This gene produces a protein called "beta-catenin", which is present in various cells and tissues within the body. It is important for cell adhesion, cell communication, cell signaling, and in the normal development and function of hair follicles. [19] [20] [21]
Treatment methods include occupational therapy, physical therapy, speech therapy, assistive services, constant monitoring and family counseling. [22] [23]
This condition affects 1 out of 50,000 children worldwide. [24]
The following list comprises some cases of severe intellectual disability-progressive spastic diplegia syndrome (from the OMIM page for this condition):
In 2004, Tucci et al.[ full citation needed] made an animal model consisting of mice (named "batface") with a heterozygous mutation (later named "T653K") located in the C-terminal amardillo repeat of the CTNNB1 gene. Said mice exhibited craniofacial dysmorphisms such as short nose, broad face, short anteroposterior axis. Altered brain morphology with signs such as larger structures of the deep brain, reduced volume of the cerebellum and the olfactory bulb, and corpus callosum hypoplasia. Altered behavior and cognitive function with signs such as motor defects, less complexity in vocalization, poor hippocampus-dependant memory, and deficits in pre+pulse inhibition. In vitro studies revealed that the T653K mutation 'disrupted the association between CTNNB1 and cadherin', which was consistent with a "dominant-negative effect". Abnormally high length and number of neurons, alongside diminished dendritic branching was present in the brains of heterozygous mutant mice. CTNNB1 knockdown (by the usage of siRNA) resulted in decreasing of neuronal processes and length, which lead the researchers to believe T653K is a loss-of-function type of mutation. Electrophysiologic tests showed that the neurons of mutated mice exhibited higher neural network excitability alongside decreased efficiency of functional connectivity. These results showed that CTNNB1 is important in various aspects of neurodevelopmental and synaptic function. [26]
The following list comprises some of the organizations which help patients with this condition:
The CTNNB1 Foundation is an organization for the parents of children with the condition whose main goal is to be able to give children with CTNNB1 syndrome the opportunity of a gene therapy treatment. [32]
The CTNNB1 Syndrome Awareness Worldwide is an organization which aims at increasing awareness of this condition across the world. It also provides information on CTNNB1 syndrome to parents of children with the condition. [33]
The CureCTNNB1 is an organization which helps raise funding for research on CTNNB1 syndrome. [34]
This condition has been covered by a small number of news networks from Spain. [35] [36] [37] [38] [39]
{{
cite web}}
: CS1 maint: numeric names: authors list (
link)
Severe intellectual disability-progressive spastic diplegia syndrome | |
---|---|
Other names | CTNNB1 syndrome, CTNNB1-related intellectual disability, Intellectual disability, autosomal dominant 19 [1] |
Specialty | Medical genetics, Pediatry |
Causes | Genetic mutation |
Frequency | Rare, only 1 out of 50,000 live births have this condition |
Severe intellectual disability-progressive spastic diplegia syndrome is a rare novel genetic disorder characterized by severe intellectual disabilities, ataxia, craniofacial dysmorphisms, and muscle spasticity. [2] It is a type of autosomal dominant syndromic intellectual disability. [3] [4] [5] [6] [7]
Individuals with this condition typically show severe intellectual disability, motor delays, severe speech delay and difficulties, infancy-onset hypotonia affecting the trunk, progressive hypertonia affecting the distal limbs, severe progressive microcephaly, autistic-like symptoms, aggressive behavior towards others and/or oneself, sleep abnormalities, and mild facial dysmorphisms such as a broad nose, hypoplastic alae nasi, an elongated/flattened philtrum, and a thin upper lip. [8] [9]
Other symptoms include seizures, nearsightedness, farsightedness, strabismus, syringomyelia, ventriculomegaly, corpus callosum hypoplasia, hearing difficulties, and a delay in CNS myelination. [10]
In rarer cases, a child with the condition might be born with polydactyly. [11]
Most symptoms which characterize this condition arise as a result of the profound intellectual disability associated with this condition, these symptoms can cause more complications, such as communication difficulties, poor school performance, etc. [8]
This condition can be diagnosed through physical examination and genetic testing.
This condition is caused by heterozygous mutations in the CTNNB1 gene, located in the short arm of chromosome 3. [12] [13] [14] [4] [15] The condition, although genetic, is typically not inherited, except in rare cases where it is, [16] as it is usually the result of a de novo mutation. [17] Insertions, deletions, and other types of mutations have been reported. [18]
This gene produces a protein called "beta-catenin", which is present in various cells and tissues within the body. It is important for cell adhesion, cell communication, cell signaling, and in the normal development and function of hair follicles. [19] [20] [21]
Treatment methods include occupational therapy, physical therapy, speech therapy, assistive services, constant monitoring and family counseling. [22] [23]
This condition affects 1 out of 50,000 children worldwide. [24]
The following list comprises some cases of severe intellectual disability-progressive spastic diplegia syndrome (from the OMIM page for this condition):
In 2004, Tucci et al.[ full citation needed] made an animal model consisting of mice (named "batface") with a heterozygous mutation (later named "T653K") located in the C-terminal amardillo repeat of the CTNNB1 gene. Said mice exhibited craniofacial dysmorphisms such as short nose, broad face, short anteroposterior axis. Altered brain morphology with signs such as larger structures of the deep brain, reduced volume of the cerebellum and the olfactory bulb, and corpus callosum hypoplasia. Altered behavior and cognitive function with signs such as motor defects, less complexity in vocalization, poor hippocampus-dependant memory, and deficits in pre+pulse inhibition. In vitro studies revealed that the T653K mutation 'disrupted the association between CTNNB1 and cadherin', which was consistent with a "dominant-negative effect". Abnormally high length and number of neurons, alongside diminished dendritic branching was present in the brains of heterozygous mutant mice. CTNNB1 knockdown (by the usage of siRNA) resulted in decreasing of neuronal processes and length, which lead the researchers to believe T653K is a loss-of-function type of mutation. Electrophysiologic tests showed that the neurons of mutated mice exhibited higher neural network excitability alongside decreased efficiency of functional connectivity. These results showed that CTNNB1 is important in various aspects of neurodevelopmental and synaptic function. [26]
The following list comprises some of the organizations which help patients with this condition:
The CTNNB1 Foundation is an organization for the parents of children with the condition whose main goal is to be able to give children with CTNNB1 syndrome the opportunity of a gene therapy treatment. [32]
The CTNNB1 Syndrome Awareness Worldwide is an organization which aims at increasing awareness of this condition across the world. It also provides information on CTNNB1 syndrome to parents of children with the condition. [33]
The CureCTNNB1 is an organization which helps raise funding for research on CTNNB1 syndrome. [34]
This condition has been covered by a small number of news networks from Spain. [35] [36] [37] [38] [39]
{{
cite web}}
: CS1 maint: numeric names: authors list (
link)