Table 1.
Clinical Features and Genetic Findings of the HH Cohort
| ICM_242 | ICM_246 | ICM_264 | ICM_239 | ICM_55 | ICM_194 | ICM_186 | ICM_212 | ICM_171 | |
| Gene | GLI3 | GLI3 | GLI3 | GLI3 | OFD1 | OFD1 | PRKACA | TNK2 | Unsolved |
| Variant (HGVSp) | p.I749Mfs*29 | p.Q813* | p.L859* | p.E1147* | p.K240Gfs*8 | p.G728Sfs*92 | p.Y331_E332delins* | p.M171T | — |
| Variant (HGVSc) | c.2247_2250del | c.2437C>T | c.2575del | c.3439G>T | c.718_719del | c.2170_2177dup | c.993_995del | c.512T>C | — |
| Blood VAF | NA | 0% | NA | 0% | NA | 0% | 0% | 49% | — |
| Brain VAF | 26% | 20% | 25% | 28% | 58% | 46% | 19% | 84% | — |
| HH type | III | II | IV | II | II | IV | IV | IV | II |
| Syndromic features | No | No | Polydactyly, syndactyly | No | No | No | No | No | No |
| Age at sz onset | 0–6m | 0–6m | 0–6 m | 1–2 y | 6–12 m | Birth | Birth | Birth | 1-2 y |
| Type of seizures | Gelastic epilepsy-plus (initial gelastic and dacrystic seizures at m3; complex focal seizures at y3) | Gelastic epilepsy-plus (initial gelastic and dacrystic seizures at m3; infantile spasms at m7) |
Gelastic epilepsy-plus (initial gelastic seizures at m1; complex focal seizures at y11) | Gelastic epilepsy-plus (initial gelastic seizures at y2; complex focal seizures at y5) | Gelastic epilepsy | Gelastic epilepsy | Gelastic epilepsy (gelastic and dacrystic seizures) | Gelastic epilepsy (gelastic and dacrystic seizures) | Gelastic epilepsy only (from y1), one-year seizure free after first surgery at y2, then complex focal seizures (nongelastic) |
| No. of sz/day | 2–3 | 2–3 | 2–4 | 6–9 | 5–8 | 4 | 80 | 70 | 2 |
| Neuropsychological comorbidities | Developmental delay | Mild motor instability | Memory impairments | Hyperactivity, attention deficits | No | Mild behavioral disorder | Mild intellectual deficit, severe behavioral disorder, rage attacks | Mild intellectual deficit, behavioral disorder, rage attacks | Memory impairments, attention deficits, psychomotor delay |
| No. of surgeries | 2 | 1 | 2 | 1 | 1 | 1 | 4 | 1 | 2 |
| Age at surgery | 7 y | 1 y | 11 y | 5 y | 10 y | 5 y | 7 y | 1 y | 22 y |
| Duration of the epilepsy | 7 y | 1 y | 11 y | 3 y | 10 y | 5 y | 7 y | 1 y | 22 y |
| Engel score (FU) | III (6 y) | I (1 y) | I (1 y) | I (1 y) | I (6 y) | III (1 y) | I (8 y) | III (2 y) | I (2 y) |
Abbreviations: del = deletion; dup = duplication; fs = frameshift; FU = follow-up duration; HGVSc = cDNA change annotation; HGVSp = protein change annotation; HH = hypothalamic hamartoma; ins = insertion; m = months; NA = not available; sz = seizures; VAF = variant allele frequency; y = years.
RefSeq references are GLI3: NM_000168.6, OFD1: NM_003611.3, PRKACA: NM_002730.4, and TNK2: NM_001382273.1. Disconnection was performed in all cases; patients ICM_212 and ICM_186 also had a surgical resection. The Engel score was used to classify the outcome of the epilepsy surgery. In case of multiple surgeries, age at surgery refers to the last surgery.