TABLE 1.
Clinical features of patients with de novo VAMP2 mutations
| Patient number | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
| Variant | Heterozygous de novo C.166C>T, p.Arg56X | Heterozygous de novo c.217G>T, p.Gly73Trp | Heterozygous de novo c.167G>T, p.Arg56Leu | Heterozygous de novo c.337_341 deletion TACTT p.Tyr113Gln frameshift, creating stop codon 12 | Heterozygous de novo c.1A>G, p. Met1? |
| Predicted change | Premature truncation, causing haploinsufficiency | Missense mutation, causing dominant-negative effect | Missense mutation, causing dominant-negative effect | Frameshift deletion creating a premature stop codon, causing haploinsufficiency | Elimination of initiator methionine could result in no protein, truncated protein, most likely haploinsufficiency |
| Age | 20 | 39 | 5 | 6 | 5 |
| Gender | F | M | M | M | M |
| Age of presentation | Infancy | 3 Years | Unknown | 18 Months | 1 Year |
| Clinical seizures | No | Generalized convulsions | Infantile spasms, focal, and tonic seizures | No | No |
| EEG | Reduced organization or normal | Excessive generalized slowing | Burst suppression, hypsarrhythmia | Not done | Not done |
| Visual deficits | Visual acuity deficits | Retinitis pigmentosa | CVI | None | Hypermetropia and astigmatism |
| Speech impairment | No | Echolalia | Nonverbal | Speech delay | Speech delay |
| Movement disorder | Catatonia | Nystagmus, progressive ataxia, tremor | No | No | No |
| Dysautonomia | Autonomic and small fiber neuropathy | Not tested | Frequent unexplained fevers, no formal testing | Not tested | Not tested |
| Psychiatric features | Hallucinations, delusions, anxiety, depression | Obsessive-compulsive tendencies | Unable to assess | Hyperactivity, impulsivity | Hyperactivity, impulsivity |
| Behavioral disturbances | Aggressive outbursts, self-injurious behavior | No | Unable to assess due to severe ID | Aggressive outbursts, self-injurious behavior | Aggressive outbursts |
| Autistic features | Yes | Yes | Unable to assess due to severe ID | Yes | No |
| Brain imaging | Normal | Periventricular FLAIR hyperintensities | Hypoplastic corpus callosum | Not done | Normal |
| Ancillary studies | EMG with reduced sympathetic skin responses | None | None | None | None |
| Global DD | Yes | Yes | Yes | Yes | Yes |
| Dysmorphisms | Mild hypertelorism | None | Growth restricted | Short stature | None |
| Level of independence | Performs all ADLs | Independent in most ADLs | Completely dependent | Age appropriate | Age appropriate |
Note: Variants were reported through whole exome testing by GeneDx, where c. designates a location in the cDNA and p. designates a location in the predicted protein.
Abbreviations: ADL, activities of daily living; DD, developmental delay; EEG, electroencephalography; EMG, electromyography; ID, intellectual disability.