Table 1.
Genetic diagnosis and phenotype in five familial cases
| Case # (gender) | Gene (Ref Seq) | Genetic variant | Inheritance | Seizures, type | Age of onset, months | Phenotype | EEG data | Brain MRI | Additional information |
|---|---|---|---|---|---|---|---|---|---|
| 1 (f) | KCNQ2 (NM_172107.4) |
c.796_797insGTGCTGTTTCTGCCCTGCCCTCCCTGCCTGGGCTGGAACTCAATAA (p.Asp266GlyfsTer80) |
AD, heterozygous | Focal, tonic | Infancy | PMD | Diffuse generalized discharge of epileptiform spike-wave activity of a continued nature along the left temporal leads with spread to the right homologous leads, also in the anterior-central regions | Expansion of the lateral ventricles, a cyst of the velum interpositum | Aunt (II-1) and grandmother (I-1) on the proband’s mother’s side, sibling (III-3) with epilepsy |
| 2 (f) | WWOX (NM_016373.4) |
c.911C>A (p.Ser304Tyr) c.230+1G>T (Splice donor) |
AR, compound heterozygous | Focal | 1 | PMD, spastic ataxia | Spike-slow wave complexes in the right parietotemporal leads | Moderate mixed hydrocephalus, atrophy of the cerebral hemisphere, post-hypoxic encephalopathy | Sibling (II-3) with epilepsy and spastic ataxia, died at the age of 11 months |
| 3 (f) | CACNA1B (NM_000718.4) |
c.390+1_390+2insACGACACGGAGCCCTATTTCATCGGGATCTTTTGCT (Splice Donor) c.501C>G (p.Asn167Lys) |
AR, compound heterozygous | Generalized, tonic | Infancy | PMD, SD | Diffuse delta activity | - | Sibling (III-2) and cousin (III-1) with epilepsy. The proband’s mother (II-4) had seizures during pregnancy. The proband’s grandfather (I-2) had several episodes of seizures after a traumatic brain injury in a car accident |
| 4 (f) | PCDH19 (NM_001184880.2) | c.1018A>G (p.Asn340Asp) | XL, heterozygous | Clonic-tonic | 11 | PMD, SD, aggression, resistance to valproate | Spike-slow wave complexes in the central-frontal-temporal region bilaterally | - | Three female siblings (II-2-4) with epilepsy |
| 5 (f) | SLC12A5 (NM_020708.5) | c.2930A>G (p.Gln977Arg) | AD, heterozygous | Generalized | 36 | PMD, SD | Periodic diffuse slow waves, low-amplitude single and grouped spike-slow wave complexes in the right central and temporal leads, rarely spreading to the right parts of the brain | Minimal post-hypoxic changes in the white matter of the cerebral hemispheres | Two female siblings (III-1,2) with epilepsy, one of them died at the age of 3 y 4 m (III-2). Paternal cousins (III-4,5) died in infancy from cerebral palsy |
Note: AD, autosomal dominant; AR, autosomal recessive; XL, X-linked; PMD, psychomotor delay; SD, speech delay; f, female