''SYT1''-associated neurodevelopmental disorder, also known as Baker-Gordon Syndrome, is a rare genetic disorder caused by mutations in the synaptotagmin-1 (''SYT1'') gene.

Signs and symptoms

Patients present with neurodevelomental impairments and symptoms including: * Infantile

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...

* Congenital ophthalmic abnormalities * Childhood onset hyperkinetic movement disorder * Stereotypical motor behaviour * Moderate to profound

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, c ...

or intellectual disability * Sleep disturbance * Episodic agitation Epileptic seizures are not a feature of this disorder (despite abnormal

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

) and head circumference is typically normal.

Genetics

This condition is caused by

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in the ''SYT1'' gene, located on the long arm of chromosome 12 (12q21.2), which are inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

fashion.

Pathogenesis

Synaptotagmin-1 is a predominantly presynaptic Ca²⁺-sensor involved in synaptic vesicle

exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...

and

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

. In ''SYT1''-associated neurodevelopmental disorder, mutations disrupt synaptotagmin-1 function causing a reduction in

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

release Release may refer to: * Art release, the public distribution of an artistic production, such as a film, album, or song * Legal release, a legal instrument * News release, a communication directed at the news media * Release (ISUP), a code to ident ...

Diagnosis

This disorder may be suspected on the basis of the clinical features listed above and abnormal

recording. Diagnosis is made through

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

with

sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...

of the ''SYT1'' gene.

Management

At present, only supportive management of symptoms is available as there is no known curative treatment for this condition.

History

The first case of ''SYT1''-associated neurodevelopmental disorder was described in 2015 and it was classified as a syndrome in 2018. It was named after Sarah Gordon and Kate Baker, who first discovered and described it.

References

{{reflist Neurological disorders Genetic diseases and disorders Rare syndromes Autosomal dominant disorders