Table 1 Molecular data and patient phenotypes
Patient 1 / ID | Patient 2 / ID | Patient 3 / EE | Patient 4 / ID | Patient 5 / EE | Published BFNIE family | |
|---|---|---|---|---|---|---|
Previous publication | Rauch et al. 2012 ER8490 | Rauch et al. 2012 ZH60991 | Hackenberg et al. 2014 ZH62611 | Wolff et al. 2017 Patient 63 | Papuc et al. 2018 ID42680 | Heron et al. 2002; Functional characterization by Scalmani et al. 2006, Xu et al. 2007, Misra et al. 2008, Berecki et al. 2018 |
Additional reports on the same variant | Li et al. 2016 (due to a repeat shift described as p.D609fs), ID | Functional studies by Ben-Shalom et al. 2017 | Dimassi et al. 2016 Matalon et al. 2014 Wolff et al. 2017 All EE | – | – | |
Type of variant | het. frameshift | het. missense | het. missense | het. stop | het. missense | het. missense |
Inheritance | de novo | de novo | de novo | de novo | de novo | Inherited from a parent |
cDNA levela | c.1831_1832delCT | c.2809C>T | c.4025T>C | c.5147G>A | c.5408A>G | c.4687C>G |
Protein level | p.(L611Vfs*35) | p.(R937C) | p.(L1342P) | p.(W1716*) | p.(E1803G) | p.(L1563V) |
rs number (dbSNPb) | unreported | rs796053197 | rs796053134 | unreported | unreported | rs121917750 |
Chromosomal position (hg19) | chr2:166179821–166179822 | chr2:166201311 | chr2:166231247 | chr2:166245463 | chr2:166245724 | chr2:166243391 |
Allele Frequency (GnomADc) | unreported | unreported | unreported | unreported | unreported | unreported |
Conservationd, location in protein | / | high, DII S5–6 | high, DIII S5 | / | high, C-terminus | high, DIV S2 |
Established Prediction toolse | / | probably damaging | probably damaging | / | probably damaging | probably damaging |
Age at last investigation | 18y 1m | 22y 9m | 6y 8m | 24y 4m | 16y 4m | |
Gender | male | female | female | female | male | |
Consanguinity, ethnicity | no, German | no, Swiss | no, Japanese/Swiss | no, Swiss | no, Swiss | |
Pre- or perinatal anomalies | none | none | none | none | none | |
Gestational age (weeks) | 41 | 40 3/7 | 38 5/7 | term | 41 1/7 | |
Birth weight / length / HC | 3600 g / 52 cm / 35 cm | 3800 g / 51 cm / NA | 2970 g / 48 cm / 36 cm | 3150 g / NA / NA | 4120 g / 51 cm / NA | |
Intellectual disability | yes (IQ 58) | yes (IQ < 50) | yes, severe | yes, mild reading capital letters, calculating with numbers up to 10 | yes, severe | |
Autistic features | yes | yes | NA | yes | NA | |
Other abnormal behavior | compulsive stereotypies, autoaggressive behavior | compulsive stereotypies, autoaggressive behavior | none | recurrent episodes of mutism and psychotic episodes | none | |
Developmental delay Age of indep. walking Age of first words Speech development | yes 13 m 12 m Speaks sentences | yes 24 m 24 m Simple sentences | yes no indep. sitting or walking - no speech | yes 24 m delayed | yes no indep. sitting or walking - no speech | |
Seizures (onset) | none | none | yes (diagnosis at 5 m) | none | yes (day 3) | |
Seizure type | / | / | myoclonic / tonic | / | myoclonic / tonic | |
Course of epilepsy | / | / | at least 3 seizures per day, pharmacoresistant | / | 1–7 seizures per day, pharmacoresistant | |
Acquired microcephaly | no | no | yes | no | no | |
Muscle tone abnormalities, movement disorders | none | hypotonia | severe hypotonia, choreoathetotic movements | none | spasticity, bilateral contractures of knees | |
Dysmorphisms | long face, narrow palpebral fissures, and relatively thick eyebrows, narrow palate, inverted nipples, tapering fingers | long face, narrow palpebral fissures, mild brachymetacarpalia Dig. IV-V, tapering fingers | none | NA | high, narrow palate | |
Other health problems | hyperopia | myopia | OSAS, scoliosis, hip dysplasia left, hip subluxation right, recurring respiratory infections | none reported | cortical visual impairment, gastro-jejunal tube | |
EEG | normal | NA | multifocal sharp wave activity, hypsarrhythmia | normal | frontocentral spike-wave activity on both sides, burst suppression | |
MRI | pinealis cyst | NA | progressive brain atrophy | normal | normal at age 4d, generalized supra- and infratentorial atrophy, bilateral hippocampal atrophy, left-sided hippocampal sclerosis and atrophy of corpus callosum at age 14y |