Table 7.
Summary of the Clinical Features of Individuals with DNMs in RAB11A (GenBank: NM_004663.4), GABBR2 (GenBank: NM_005458.7), and SNAP25 (GenBank: NM_003081.3)
| Individual | Gender | Age at Last Examination | Gene | DNM (Detection) | Cognitive and Behavioral Features | Epilepsy Diagnosis | Age at Seizure Onset | Seizure Types | AEDs | EEG | Brain MRI | Associated Neurological Features and Seizure Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HK055 | male | 5.5 years | RAB11A | c.71A>G (p.Lys24Arg) (WES) | GDD, moderate ID | no seizures | NA | NA | NA | abnormal background activity, no epileptic charges | central brain atrophy, bilateral periventricular white-matter damage, thin CC | acquired microcephaly, axial hypotonia, obesity, aggressive behavior |
| HSJ0637 | female | 9.5 years | RAB11A | c.244C>T (p.Arg82Cys) (WGSa) | GDD, severe ID | IS | 4 months | M, ES, Fo | NZP, CLB, VGB, TPM, VPA, LEV | modified hyps., M, diffuse slowing with M spikes | atrophy, partial agenesis of CC, delayed myelination, decreased NAA | acquired microcephaly, axial hypotonia |
| 24631 | male | 4 years | RAB11A | c.461C>T (p.Ser154Leu) (WESb) | moderate GDD | no seizures | NA | NA | NA | NA | partial agenesis of the CC | distractible, possible ADHD |
| 84049 | female | 9 years, 11 months | RAB11A | c.461C>T (p.Ser154Leu) (WESb) | moderate ID | no seizures | NA | NA | NA | NA | ND | possible hyperactivity, obesity |
| HSJ0048 | male | 14 years | GABBR2 | c.2077G>T (p.Gly693Trp) (WGSa) | severe GDD, severe ID | DEE, IS | 11 months | FIA, ES, GTC | CBZ, VGB, VPA, TPM, CLB, PHT, LEV, LCM, LTG | modified hyps. | increased sub-arachnoid spaces | axial and limb hypotonia, hyporeflexia, scoliosis, hypersalivation |
| HSJ0745 | male | 23 years | SNAP25 | c.496G>T (p.Asp166Tyr) (WGSa) | GDD, moderate ID | DEE | 18 months | GTC, FIA | VPA, CLB | gen. SW, CSWS | mild diffuse cortical atrophy | apneas, bradycardia, severe constipation, minor dysmorphic traits, no seizures for 2 years on VPA |
Underlining indicates treatment with clinical response (decreased seizure frequency or severity). Abbreviations are as follows: NA, not applicable; ND, not done; WES, whole-exome sequencing; WGS, whole-genome sequencing; GDD, global developmental delay; ID, intellectual disability; IS, infantile spasms; DEE, developmental and epileptic encephalopathy; M, myoclonic; ES, epileptic spasm; Fo, focal; FIA, focal impaired awareness; GTC, generalized tonic-clonic; AED, anti-epileptic therapy; NZP, nitrazepam; CLB, clobazam; VGB, vigabatrin; TPM, topiramate; VPA, valproic acid; LEV, levetiracetam; CBZ, carbamazepine; PHT, phenytoin; LCM, lacosamide; LTG, lamotrigine; EEG, electroencephalography; hyps., hypsarrhythmia; gen. SW, generalized spike-wave; MRI, magnetic resonance imaging; CC, corpus callosum; ADHD, attention-deficit hyperactivity disorder; CSWS, continuous spike and wave during sleep; and NAA, N-acetylaspartate.
CENet.
DDD study.