Table 2.
Summary of the clinical, neuroimaging, and molecular findings in males with ARX mutations (n=10)
| Patient No. | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
|---|---|---|---|---|---|---|---|---|---|---|
| ID#1 | LR04-386 | LR04-272 | LR03-309 | LR02-457 | LR11-422 | LR11-425 |
LR11-423 10.2790 |
LR02-310 02.2838 |
LR04-427 04.1087 |
LR03-413 03.3113 |
| Ethnicity | Caucasian | Caucasian | Asian | nd | nd | Mixed European | German/Native American/Polish | Asian | Caucasian/African-American | Eastern European (Jewish) |
| Age at last assessment | 17y | 6y | 21m | 19y | 3y | 16y | 20m | nd | nd | 13m |
| Seizure onset | Neonatal | 6w | 13w | Neonatal | 4m | 2m | 10d | 3m | 24d | 6m |
| Seizure types | T | ISS, CPS | ISS, MC, CPS | ISS, PS | ISS | ISS, CPS | ISS, CPS, PS | T, tonic spasms | T, tonic spasms | ISS, MC |
| Intractable epilepsy | + | + | + | + | + | + s/p VNS placement at 12y | + | − | + | + |
| EEG findings | Generalized atypical spike, polyspike, slow wave discharges, multifocal characteristics | HYPS, frequent electrodecrement al responses | Multifocal epileptiform discharges, disorganized background | HYPS (6w), Lennox-Gastaut- like pattern (17y) | HYPS | Focal sharps at frontoparietal areas, slow background (16y) | HYPS | HYPS | Burst suppression, generalized polyspikes | HYPS |
| CBR-CBL atrophy | + | + | + | ++ | + | − | + | − | − | + |
| Last MRI | 4y | nd | nd | 19y | nd | 12y | 14m | 2y | Infancy | 1y |
| Severe GDD | + | + | + | + | + | + | + | + | + | + |
| Tone | Spasticity (on baclofen) | Hypotonia | Severe hypotonia | Mixed (appendicular spasticity and axial hypotonia) | Axial hypotonia | Hypotonia | Axial hypotonia with opisthotonic posturing | Hypotonia | nd | Hypotonia |
| Earliest OFC – SD | nd | nd | nd | nd | nd | nd | 1–2 (11d) | nd | nd | nd |
| Last OFC – SD (age) | −0.5 (17y) | nd | −0.5–0 (3y) | nd | −1–0 (3y) | 0 (16y) | −0.5–0 (20m) | nd | nd | 0–1 (13m) |
| Postnatal MIC | − | nd | − | nd | − | − | − | nd | + | − |
| Abnormal movements | + | + | − | + | + | + | +a | − | − | − |
| Other medical problems | Tracheostomy, pneumonia | − | − | G-tube, constipation, choking (esp. at night, treated with Botox & scopolamine) | nd | − | CVI, irritability due to GER, constipation, aspiration with PO feeds at 13m (supplemental NG feeds), ↑ CPK (due to underlying movement disorder), intrauterine hiccups | CVI | Scrotal hypoplasia, ear dimples | − |
| Outcome | Alive | Alive | Alive | Alive | Alive | Alive | Alive | Alive | Alive | Alive |
| Mutation | c.333_335dup (GGC)7 (exon 2) | c. 333_335dup (GGC)7 (exon 2) | c. 333_335dup (GCG)7 (exon 2) | c. 333_335dup (GCG)7 (exon 2) | c. 333_335dup (GGC)7 (exon 2) | c. 333_335dup (GGC)7 (exon 2) | c.333_335dup (GGC)8 (exon 2) | c.429_452dup24 (exon 2) | IVS4-82_ex5 1469ins103 (intron 4/exon 5) | c. 998C>G (p.T333S) (exon 2) |
| Type | In-frame; insertion 7 polyalanine repeats | In-frame; insertion 7 polyalanine repeats | In-frame; insertion 7 polyalanine repeats | In-frame; insertion 7 polyalanine repeats | In-frame; insertion 7 polyalanine repeats | In-frame; insertion 7 polyalanine repeats | In-frame; insertion 8 polyalanine repeats | In-frame; insertion 8 polyalanine repeats | Insertion 103 bp | Missense |
| Inheritance | nd | nd | De novo | De novo | nd | nd | Maternally-inheritedb | nd | Maternally-inherited | De novo |
| Family history | nd | nd | Febrile seizures | No known neurologic problems | nd | No known neurologic problems | See below | nd | nd | 2 healthy sibs, 1 SAB |
a
This patient had PAID syndrome (paroxysmal autonomic instability with dystonia), dystonic posturing and choreoathetosis, and bilateral clonus
b
This patient’s mother is asymptomatic and has never had a brain MRI. A maternal cousin has a history of autism-spectrum disorder, seizures and DD. A maternal half-aunt had seizures at 13–14 yrs and a maternal uncle had seizures secondary to head trauma during a motor vehicle accident.
For abbreviations, see table 1