Table 1.
Clinical Features of Individuals with De Novo VAMP2 Mutations
| Individual Number Gender Age | Variant | Growth/OFC | Hypotonia/DD | ID | Epileptic Seizures | EEG | ASD | RTT-Like Features | Movement Disorder | Central Visual Defects | Speech Impairment | Brain Imaging | Additional Features |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 F 3 yr |
c.223T>C, p.Ser75Pro | normal | yes | severe | no | high-voltage delta activity, sharp wave-slow wave complexes | yes | stereotyped hand movements, absent purposeful hand movements | choreic movement, flapping, dystonic postures |
yes | absent speech | thin corpus callosum, delayed myelination | inability to walk |
| 2 M 10 yr |
c.233A>C, p.Glu78Ala | normal | yes | severe | focal seizures, GTCS | fast rhythmic activity, sharp wave-slow wave complexes | yes | body rocking, head banging, screaming, absent purposeful hand movements | generalized chorea |
yes | absent speech | unremarkable | abnormal behavior, self-injury, inability to walk |
| 3 M 13yr |
c.230T>C, p.Phe77Ser | normal | yes | severe | infantile spasms, convulsive status epilepticus |
disorganized EEG paroxysms | yes | stereotyped hand movements, absent purposeful hand movements | choreic movement, myoclonic jerks | yes | absent speech | unremarkable | abnormal behavior, inability to walk, severe constipation |
| 4 M 14yr |
c.128_130delTGG, p.Val43del | normal | yes | moderate | focal seizures | generalized and multifocal abnormalities | yes | stereotyped hand movements (wringing), absent purposeful hand movements | no | no | only 5–10 spoken words | unremarkable | clumsiness, abnormal behavior |
| 5 F 3 yr |
c.135_137delCAT, p.Ile45del | normal | yes | moderate | no | disorganized EEG paroxysms | yes | stereotyped hand movements (washing) | no | no | only 5 spoken words | unremarkable | abnormal behavior |
Abbreviations are as follows: ASD = autism spectrum disorder; DD = developmental delay; EEG = electroencephalography; FC = focal seizures; GTCS = generalized tonic-clonic seizures; ID = intellectual disability; and OFC = occipital-frontal circumference. Variants are named according to the GenBank: NM_014232 reference transcript.