SYT1-associated neurodevelopmental disorder

Patients present with neurodevelomental impairments and symptoms including:

• Infantile hypotonia
• Congenital ophthalmic abnormalities
• Childhood onset hyperkinetic movement disorder
• Sterotypical motor behaviour
• Moderate to profound developmental delay or intellectual disability
• Sleep disturbance
• Episodic agitation

Epileptic seizures are not a feature of this disorder (despite abnormal EEG) and head circumference is typically normal.

This condition is caused by heterozygous mutations in the SYT1 gene, located on the long arm of chromosome 12 (12q21.2), which are inherited in an autosomal dominant fashion.

Synaptotagmin-1 is a predominantly presynaptic Ca²⁺-sensor involved in synaptic vesicle exocytosis and endocytosis. In SYT1-associated neurodevelopmental disorder, mutations disrupt synaptotagmin-1 function causing a reduction in neurotransmitter release.[1]

This disorder may be suspected on the basis of the clinical features listed above and abnormal EEG recording. Diagnosis is made through genetic testing with sequencing of the SYT1 gene.

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

The first case of SYT1-associated neurodevelopmental disorder was described in 2015[2] and it was classified as a syndrome in 2018.[1][3]