Table 3.
Clinical characteristics of patients with biallelic NRXN1 and NRXN1–NRXN2 variants
| Patients | Our proband | Zweier et al. (2009) | Harrison et al. (2011)— sibling 1 | Harrison et al. (2011)— sibling 2 | Duong et al. (2012) | Béna et al. (2013) | Imitola et al. (2014)— sibling 1 | Imitola et al. (2014)— sibling 2 |
|---|---|---|---|---|---|---|---|---|
| NRXN variants | NRXN1: c.2686C>T; p.Arg896Trp | NRXN1: 113 kb del (2:51001003–51113677) | NRXN1: 79 kb del (2:50214717–50293739) | NRXN1: 79 kb del (2:50214717–50293739) | NRXN1: 451 kb del (2:50812891–51263512) | NRXN1: 181 kb del (2:50963194–51144527) | NRXN1: 130 kb del (2:51047025–51176742) | NRXN1: 107 kb del (2:51047060–51154995) |
| NRXN2: c.3176G>A; p.Arg1059Gln | NRXN1: p.Ser979Ter | NRXN1: 287 kb del (2:51008023–51294599) | NRXN1: 287 kb del (2:51008023–51294599) | NRXN1: c.2880-1G>A; p.Tyr961ThrfsX31 | NRXN1: 401 kb del (2:50963194–51364465) | NRXN1: 135 kb del (2:51184729–51319450) | NRXN1: 174 kb del (2:51154996–51328796) | |
| Age | 49 da | 18 yr | 16 yr | 11 yr | 33 yr | 10 yr | 7 yr | 7 yr |
| Gender | F | F | F | F | M | F | M | F |
| Developmental delay | N/A | Severe | Severe | Severe | Severe | Severe | Severe | Severe |
| Seizure onset | 2 d | None | 6 mo | 4 mo | 7 mo | 6.5 yr | 5 yr | None |
| Seizure type | EIEE | None | EIEE | EIEE | IS, TC | AA, TC, HT | AA | None |
| Age of walking | N/A | 2 yr | 5 yr | None | 3 yr | 26 mo | 2 yr | 2 yr |
| Speech | N/A | None | 20–25 words | None | None | Few words | 2–10 words | 2–5 words |
| Breathing abnormality | Irregular breathing with periods of severe apnea | Hyperventilation | Hyperventilation | Breath holding | N/A | Recurrent airway infections | No | Hyperventilation |
| Stereotypies | N/A | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Constipation | N/A | Yes | Yes | Yes | N/A | Yes | Yes | Yes |
| Abnormal sleep–wake cycle | N/A | Yes | Yes | Yes | N/A | Yes | Yes | Yes |
| Brain MRI | Normal | N/A | Normal | N/A | Moderate atrophy and cyst deflecting right hippocampus | Normal | Normal | – |
| Other | Extreme lethargy and hypertonicity of the extremities | Strabismus, protruding tongue, excessive drooling, broad mouth | GORD, scoliosis, pulmonary stenosis, hypotonia, early-onset, puberty, self-harm behavior | GORD, scoliosis, pulmonary stenosis, hypotonia, early-onset, puberty | Strabismus, perceptive hearing impairment, autism, dysmorphic features | Recurrent FS during her first 2 yr, feeding problems and GORD, autism, no obvious dysmorphic features | Dysphagia, aggressive and self-harm behavior, and ventricular septal defect | Aggressive behavior, strabismus, hypotonia and ataxia |
(AA) atypical absence, (EIEE) early infantile epileptic encephalopathy, (F) female, (GORD) gastroesophageal reflux disease, (HT) hypotonic seizures, (IS) infantile spasms, (M) male, (MRI) magnetic resonance imaging, (N/A) not available, (TC) tonic–clonic seizures.
aDeceased.