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Table 1 Molecular data and patient phenotypes

From: Further corroboration of distinct functional features in SCN2A variants causing intellectual disability or epileptic 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  
  1. Abb: / not relevant for this case; D domain, het heterozygous, EEG electroencephalogram, HC head circumference, m months, MRI magnetic resonance imaging, NA not available, S segment; y years
  2. aaccording to reference sequence NM_021007
  3. b https://www.ncbi.nlm.nih.gov/SNP
  4. c http://gnomad.broadinstitute.org
  5. daccording to Alamut Visual v.2.8.1
  6. ePolyphen2, MutationTaster, SIFT assessed by Alamut Visual v.2.8.1