Table S1 Detailed Molecular, Clinical and Neuroradiological Features of the 30 New Patients

Table S1 Detailed molecular, clinical and neuroradiological features of the 30 new patients with FOXG1 syndrome. Patients ID 1-8

ID / 1 / 2 / 3 / 4 / 5 / 6 / 7 / 8
Family ID / 1 / 2 / 3 / 4 / 5 / 6 / 7 / 8
Sex / Male / Male / Male / Female / Female / Female / Male / Female
Age at last follow-up / 40 / 51 / 33 / 100 / 105 / 39 / 72 / 45
Indication for genetic diagnostics / developmental delay, microcephaly, dyskinesia, cMRI: corpus callosum anomaly / developmental delay, microcephaly, epilepsy, cMRI: simplified gyral pattern, delay of myelinisation / developmental delay, microcephaly, hypotonia, epilepsy / developmental delay, microcephaly, hypotonia, cMRI: pachygyria, corpus callosum anomaly / developmental delay, microcephaly, hypotonia, cMRI: pachygyria / developmental delay, microcephaly, epilepsy, strabism, cMRI: corpus callosum anomaly / developmental delay, microcephaly, hypotonia, stereotypic movements, epilepsy / severe developmental delay, neonatal hypotonia, poor eye contact, impaired social interaction, microcephaly, cMRI: corpus callosum anomaly, septooptic dysplasia
AA Change / p.(Q86Rfs*106) / p.(Q72*) / p.(E136*) / p.(E154Gfs*301) / p.(E129Sfs*63) / p.(E154Rfs*38) / p.(E154Gfs*301) / p.(E154Gfs*301)
Method / FOXG1 Sanger sequencing / FOXG1 Sanger sequencing / Exome / FOXG1 Sanger sequencing / FOXG1 Sanger sequencing / FOXG1 Sanger sequencing / NGS panel epileptic encephalopathy / NGS panel epilepsy
Additional genetic analyses / chromosome analysis, array-CGH / chromosome analysis, subtelomeric microdeletion analysis, array-CGH, MECP2 / chromosome analysis, Angelman-methylation analysis, MECP2, panel mitochondrial nuclear genes / chromosomee analysis, TUBA1A, FKTN / chromosome analysis, subtelomeric microdeletion analysis, array-CGH, Angelman-methylation analysis, MECP2 / chromosome analysis, MECP2, TCF4 / chromosome analysis, array-CGH, Angelman-methylation analysis, ARX, CDKL5, TH, MECP2 / chromosome analysis
Weight at birth in g / 3530 / 2380 / 3600 / 2950 / 2700 / 2930 / 3250 / 2480
Weight at birth (SD) / -0.2 / -1.6 / -0.2 / -0.5 / -1.5 / -0.1 / -0.1 / -1.6
Length at birth in cm / 52 / 45 / 50.2 / 48 / 50 / 52.5 / 48 / 48
Length at birth (SD) / -0.2 / -2.2 / -0.5 / -1.0 / -0.5 / 1.3 / -1.3 / -1.0
HC at birth in cm / 33.5 / 31 / - / 32 / 31.5 / 32.5 / 35 / 32
HC at birth (SD) / -1.6 / -2.3 / - / -1.8 / -2.4 / -1.0 / -0.1 / -1.8
Gestational Age / 40 / 37 / 39 / 38 / 39 / 37 / 38 / 38
Weight at follow-up (SD) / -2.34 / -2.8 / -1.7 / -2.41 / -1.9 / -2.94 / -2.78 / -1.3
Length at follow-up (SDS) / -1.19 / -2.4 / -0.7 / -1.26 / -1.2 / -2.54 / -2.98 / -3.14
BMI (SD) / -1.98 / -1.1 / -2.4 / -2.5 / -1.34 / -1.55 / -0.8 / -2.37
HC at follow-up (SD) / -3.77 / -5.2 / -4.1 / -4.26 / -4.84 / -6.75 / -4.53 / -0.56
Age at sitting in months / - / 48 / 24 / 48 / 24 / - / - / -
Sitting at follow-up / - / assisted / assisted / assisted / assisted / absent / absent / -
Age at walking in months / - / - / - / - / 60 / - / - / -
Walking at follow-up / absent / absent / absent / absent / assisted / absent / absent / absent
Functional hand use at follow-up / present / present / absent / present / present / absent / absent / absent
Speech at follow-up / present / absent / present / absent / absent / present / absent / absent
Age starting expressive speech in months / 26 / - / 21 / - / - / 54 / - / -
Number of words spoken / 6 / 0 / 4 / 0 / 0 / 4 / 0 / 0
Stereotypic movements / present / present / absent / present / present / present / present / present
Dyskinesia / present / present / present / present / present / present / present
Hypotonia / present / present / present / present / present / present / present / present
Spasticity / absent / present / absent / present / present / present / present
Strabism / present / present / present / present / present / present / present / present
Nystagmus / absent / absent / absent / absent / absent / absent / absent
Abnormal sleep patterns / present / absent / present / present / present / present / - / present
Social interaction / present / present / absent / present / present / present / - / present
Eye contact / poor / poor / absent / good / poor / absent / - / poor
Unexplained episodes of crying / present / present / present / absent / present / present / present / present
Epileptic seizures: Age at onset in months / - / 21 / 24 / - / 55 / 6 / 11 / -
Seizures / absent / present / present / absent / present / present / present / present
Types of seizures / - / focal, generalised tonic-clonic seizures / infantile spasms, generalized tonic seizures, generalized tonic-clonic activity, febrile seizures / - / n.r. / focal-tonic, tonic-clonic generalised seizures / myoclonic seizures / n.r.
Antiepileptic treatment / no / n.r. / phenobarbital, levetiracetam, vigabatrin, oxcarbazepine, CBD, valproate, clobazam / no / n.r. / zonisamide, acetazolamide / yes / n.r.
Antiepileptic treatment response / - / yes / drug resistant / - / yes / yes / low / yes
Feeding difficulties / present / present / G-Tube / present / present / present / present / present
Gastroesophageal reflux / absent / absent / present / present / present / absent / present / -
Aspiration / - / absent / absent / absent / present / - / - / -
Constipation / present / absent / present / present / present / present / present / present
Hypersalivation / present / absent / present / present / present / present / - / -
Bruxism / present / present / present / present / present / present / - / -
Abnormal breathing patterns / absent / absent / absent / absent / absent / present / present / -
Kypho-/scoliosis / present / absent / absent / present / absent / - / absent / absent
Corpus callosum anomalies / present / absent / present / present / absent / present / present / present
Cortical anomalies / present / absent / absent / present / present / present / present / present

-, missing data

Table S1 Detailed molecular, clinical and neuroradiological features of the 30 new patients with FOXG1 syndrome. Patients ID 9-16

ID / 9 / 10 / 11 / 12 / 13 / 14 / 15 / 16
Family ID / 9 / 10 / 11 / 11 / 13 / 14 / 15 / 16
Sex / Male / Female / Male / Female / Female / Male / Male / Female
Age at last follow-up / 61 / 30 / 82 / 34 / 85 / 93 / 192 / 62
Indication for genetic diagnostics / developmental delay, microcephaly, cMRI: corpus callosum anomaly / developmental delay, microcephaly, cMRI: simplified gyral pattern / developmental delay, hypotonia, strabism, epilepsy / developmental delay, microcephaly, hypotonia / developmental delay, hypotonia, epilepsy, cMRI: delayed myelination / developmental delay, regression, epilepsy / profound developmental delay, epilepsy, cleft palate, cMRI: corpus callosum anomalie / developmental delay, hypotonia, infantile spasms, cMRI: corpus callosum anomaly
AA Change / p.(E154Gfs*301) / p.(E173*) / p.(K181N) / p.(K181N) / p.(P182Q) / p.(S185C) / p.(N187K) / p.(N187K)
Method / NGS panel epilepsy and epileptic encephalopathy / Trio-Exome / NGS panel microcephaly and epileptic encephalopathy / FOXG1 Sanger segregation / NGS panel epileptic encephalopathy / NGS panel epileptic encephalopathy / Trio-Exome / Trio-Exome
Additional genetic analyses / panel microcephaly, panel holoprosencephaly / array-CGH, MYCN, panel microcephaly / chromosome analysis, array-CGH, Miller-Dieker syndrome, subtelomeric microdeletion analysis, fragile X, Angelman-methylation analysis, UBE3A, MECP2, PHF6, ATRX / segregation UBE3A, FOXG1 / chromosome analysis, Angelman-methylation analysis, MECP2 / chromosome analysis, array-CGH, fragile X, Angelman-methylation analysis, UBE3A, SLC9A6, MECP2 / chromosome analysis, FISH 22q11.2, subtelomeric microdeletion analysis, array-CGH, ARX, panel peroxisomal disorders / chromosome analysis, array-CGH, fragile X, MECP2, CDKL5, POLG
Weight at birth in g / 3754 / 3860 / 3810 / 3410 / 3480 / 3615 / 4400 / 3175
Weight at birth (SD) / 0.04 / 0.73 / 0.55 / -0.11 / 0.02 / -0.02 / 1.5 / -0.7
Length at birth in cm / 52 / 55 / 50 / 50 / 52 / 50 / 54.5 / 53.3
Length at birth (SD) / -0.5 / 0.74 / -1.14 / -1.11 / 0.1 / -1.1 / 0.6 / 0.7
HC at birth in cm / 34 / 31 / 35 / - / 35 / 36 / 38 / -
HC at birth (SD) / -1.5 / -2.71 / -0.75 / 0 / 0.25 / 0.3 / 1.6 / -
Gestational Age / 40+6 / 40+6 / 40+3 / 40+5 / 40 / 39+6 / 41 / (40)
Weight at follow-up (SD) / -4.6 / 0.27 / -1.34 / -1.26 / -2.1 / -2.95 / -2.24 / -0.79
Length at follow-up (SDS) / -2.7 / -0.4 / -1.07 / -1.43 / -1.9 / 1.63 / -5.01 / 0.49
BMI (SD) / -1.02 / 0.7 / -0.98 / -0.45 / -1.2 / -2.7 / -1.4 / -2.15
HC at follow-up (SD) / -5.0 / -5.6 / -1.92 / -2.96 / -2.1 / -1.97 / -0.24 / -0.79
Age at sitting in months / - / - / 11 / 11 / 24 / 9 / - / -
Sitting at follow-up / absent / absent / unassisted / unassisted / unassisted / unassisted / absent / absent
Age at walking in months / - / - / 30 / 30 / 72 / 42 / - / -
Walking at follow-up / absent / absent / assisted / assisted / unassisted / unassisted / absent / absent
Functional hand use at follow-up / present / absent / present / present / present / present / absent / absent
Speech at follow-up / absent / absent / present / absent / absent / absent / absent / absent
Age starting expressive speech in months / - / - / 33 / - / - / - / - / -
Number of words spoken / 0 / 0 / 100 / 0 / 0 / 0 / 0 / 0
Stereotypic movements / present / absent / absent / absent / present / present / present / present
Dyskinesia / present / absent / absent / absent / present / absent / present
Hypotonia / present / present / present / present / present / present / present / present
Spasticity / absent / absent / absent / absent / absent / present / present
Strabism / present / present / present / present / absent / absent / present / absent
Nystagmus / absent / absent / absent / absent / absent / absent / absent
Abnormal sleep patterns / present / present / absent / present / present / present / present / present
Social interaction / good / good / good / good / good / absent / good
Eye contact / good / good / good / good / good / absent / poor / poor
Unexplained episodes of crying / absent / - / absent / absent / present / absent / - / -
Epileptic seizures: Age at onset in months / 11 / - / 24 / 34 / 5 / 72 / 4 / 4
Seizures / present / absent / present / present / present / present / present / present
Types of seizures / symptomatic epilepsy / - / focal seizures / febrile seizures / Status epilepticus, febrile seizures / tonic-myoclonic, tonic-clonic seizures / infantile spasms, tonic clonic seizures, absence, Lennox-Gastaut syndrome / infantile spasms, tonic seizures, myoclonic, Lennox-Gastaut syndrome
Antiepileptic treatment / valproate / - / levetiracetam, oxcarbacepine / levetiracetam / yes / 4 medications / ACTH, topiramate, zonisamide, ketogenic diet, vagal nerve stimulator, levetiracetam, valproate, azelastine, pyridoxine, clonazepam / felbamate, levetiracetam, lamotrigine, clobazam; ACTH, prednisolone, topiramate, ketogenic diet, valproate, zonisamide; vagal nerve stimulator"
Antiepileptic treatment response / good / - / good / good / yes / low / drug resistant / drug resistant
Feeding difficulties / present / G-Tube / present / absent / absent / present / G-Tube / G-Tube
Gastroesophageal reflux / present / present / absent / absent / absent / absent / absent / present
Aspiration / absent / - / absent / absent / present / absent / present / present
Constipation / present / - / absent / absent / present / absent / present / present
Hypersalivation / present / - / absent / absent / present / absent / absent / -
Bruxism / present / - / absent / present / present / absent / absent / -
Abnormal breathing patterns / present / absent / absent / absent / present / absent / absent / -
Kypho-/scoliosis / present / absent / absent / absent / present / absent / absent / -
Corpus callosum anomalies / present / present / absent / - / absent / absent / present / present
Cortical anomalies / absent / present / present / - / absent / absent / present / present

-, missing data

Table S1 Detailed molecular, clinical and neuroradiological features of the 30 new patients with FOXG1 syndrome. Patients ID 17-24

ID / 17 / 18 / 19 / 20 / 21 / 22 / 23 / 24
Family ID / 17 / 17 / 19 / 20 / 21 / 22 / 23 / 24
Sex / Female / Female / Female / Female / Male / Male / Male / Female
Age at last follow-up / 20 / 33 / 72 / 25 / 46 / 28 / 31 / 14
Indication for genetic diagnostics / developmental delay, microcephaly / developmental delay, microcephaly / developmental delay, regression, microcephaly, epilepsy, hypotonia, sleep disorder, dystrophy, cMRI: corpus callosum anomaly, delayed myelination / developmental delay, microcephaly / developmental delay, microcephaly / developmental delay, dystrophy, microcephaly, epilepsy, hypotonia, spasticity, stereotypic movements: washing hands / developmental delay, microcephaly, facial dysmorphism / developmental delay, microcephaly, failure to thrive, cMRI: delayed myelination
AA Change / p.(L189F) / p.(L189F) / p.(l194S) / p.(P198del) / p.(L204Hfs*248) / p.(Y208*) / p.(R244C) / p.(H245Tfs*78)
Method / FOXG1 Sanger sequencing / FOXG1 Sanger segregation / NGS panel epileptic encephalopathy / FOXG1 Sanger sequencing / Trio-Exome / NGS panel epileptic encephalopathy / NGS panel microcephaly / Trio-Exome
Additional genetic analyses / chromosome analysis, array-CGH, Angelman-methylation analysis, UBE3A, MECP2 / chromosome analysis, array-CGH, Angelman-methylation analysis, UBE3A, MECP2 / chromosome analysis, subtelomeric microdeletion analysis, Miller-Dieker syndrome, SMN1, SMN2, LIS1, MECP2, HESX1, SHH / Angelman-methylation analysis, UBE3A, MECP2 / NGS panel microcephaly / chromosome analysis, Miller-Dieker syndrome, Angelman-methylation analysis, subtelomeric microdeletion analysis / array-CGH / micro-array, panel nuclear-encoded mitochondrial genes, mDNA sequencing
Weight at birth in g / 2160 / 2640 / 3510 / 3040 / 3170 / 2890 / 2720 / 3270
Weight at birth (SD) / -2.4 / -1.3 / -0.2 / -0.7 / -0.7 / -0.5 / -2.3 / -0.5
Length at birth in cm / 47 / 49 / 51 / 50 / 51 / 48 / 48 / 44
Length at birth (SD) / -1.5 / -0.6 / -0.5 / -0.6 / 0.4 / -0.9 / -2.2 / -4.8
HC at birth in cm / 30 / 32 / 33 / 34 / 32.5 / 32 / 31.5 / 34
HC at birth (SD) / -3.3 / -1.8 / -1.7 / -0.5 / -2.2 / -1.6 / -3.4 / -0.6
Gestational Age / 38 / 38 / 41 / 39 / 39 / 37 / 41 / 40
Weight at follow-up (SD) / -2.45 / -2.7 / -3.1 / 0.19 / -3.18 / -1.7 / -3.62 / -0.7
Length at follow-up (SDS) / -3.58 / -1.47 / -0.95 / 1.38 / -4.2 / -1.45 / -1.8 / -2.18
BMI (SD) / -2.33 / -4.26 / -4.13 / -1.07 / -0.04 / -1.04 / -3.48 / 1.5
HC at follow-up (SDS) / -4.84 / -4.5 / -6.17 / -2.83 / -5.7 / -8.8 / -6.16 / -3.0
Age at sitting in months / 30 / 30 / - / 56 / - / - / 15 / -
Sitting at follow-up / unassisted / unassisted / absent / unassisted / absent / absent / unassisted / absent
Age at walking in months / - / - / - / - / - / - / 24 / -
Walking at follow-up / absent / absent / absent / assisted / absent / absent / assisted / absent
Functional hand use at follow-up / present / present / present / absent / absent / absent / absent / absent
Speech at follow-up / absent / absent / absent / present / absent / absent / present / absent
Age starting expressive speech in months / - / - / - / 84 / - / - / 26 / -
Number of words spoken / 0 / 0 / 0 / 20 / 0 / 0 / 5 / 0
Stereotypic movements / present / present / present / present / present / present / present / present
Dyskinesia / present / present / present / present / absent / present / present / present
Hypotonia / present / present / present / present / present / present / present / present
Spasticity / absent / absent / absent / absent / absent / present / absent / absent
Strabism / absent / absent / present / present / absent / present / present / present
Nystagmus / absent / absent / present / absent / absent / absent / present / present
Abnormal sleep patterns / absent / absent / present / present / absent / absent / present / absent
Social interaction / good / good / good / good / good / good / good / good
Eye contact / - / - / good / poor / poor / poor / good / good
Unexplained episodes of crying / absent / absent / present / absent / present / present / present
Epileptic seizure: Age at onset in months / - / - / 36 / - / - / 24 / - / -
Seizures / absent / absent / present / absent / absent / present / absent / absent
Types of seizures / - / generalized seizures / - / - / tonic febrile seizures / - / -
Antiepileptic treatment / no / no / - / - / no / no / - / -
Antiepileptic treatment response / - / - / - / - / - / - / - / -
Feeding difficulties / present / present / present / absent / present / present / present / G-Tube
Gastroesophageal reflux / absent / absent / - / - / absent / present / present / present
Aspiration / - / - / - / - / - / - / present / present
Constipation / absent / absent / present / present / present / present / absent / absent
Hypersalivation / present / absent / present / present / present / present / present / absent
Bruxism / present / present / present / present / present / absent / absent
Abnormal breathing patterns / absent / - / present / absent / absent / present / absent / present
Kypho-/scoliosis / absent / present / - / absent / present / present / absent / absent
Corpus callosum anomalies / absent / present / present / absent / present / present / - / absent
Cortical anomalies / absent / present / present / present / present / present / - / absent

-, missing data

Table S1 Detailed molecular, clinical and neuroradiological features of the 30 new patients with FOXG1 syndrome. Patients ID 25-30

ID / 25 / 26 / 27 / 28 / 29 / 30
Family ID / 25 / 26 / 27 / 28 / 29 / 30
Sex / Male / Female / Female / Female / Female / Male
Age at last follow-up / 89 / 31 / 204 / 192 / 33 / 47
Indication for genetic diagnostics / developmental delay, hypotonia, facial dysmorphism / developmental delay, epilepsy, hypotonia / epileptic encephalopathy, developmental delay, regression / developmental delay, spasticity, dyskinesia, stereotypic movements, cMRI: simplified gyral pattern / developmental delay, microcephaly, hypotonia, dystrophy / developmental delay, microcephaly, spasticity, dyskinesia
AA Change / p.(L325Ffs*130) / p.(L362Pfs*93) / p.(A381Pfs*4) / p.(G252D) / p.(Y307*) / p.(S197I)
Method / Exome / Trio-Exome / NGS panel epileptic encephalopathy / NGS panel epilepsy / FOXG1 Sanger sequencing / Trio-Exome
Additional genetic analyses / chromosome analysis, array-CGH, MECP2, Angelman-methylation analysis, UBE3A, panel X-linked mental retardation, ZEB2, TCF4 / SNP array, panel Cornelia de Lange syndrome (NIPBL, SMC1A, SMC3) / n.r. / array-CGH / chromosome analysis, array-CGH, ZFHX1B, DHCR7 / none
Weight at birth in g / 2778 / 2580 / 2860 / 3000 / 3320 / 3400
Weight at birth (SD) / -0.7 / -2.1 / -0.7 / -1.1 / -0.4 / -0.9
Length at birth in cm / 48.3 / - / 48 / - / 50 / 53
Length at birth (SD) / -0.8 / - / -1.0 / - / -0.8 / -0.42
HC at birth in cm / 33 / - / 32.5 / 31.2 / 34 / 35
HC at birth (SD) / -0.9 / - / -1.0 / -2.8 / -0.7 / -0.42
Gestational Age / 37 / (40) / 38 / 40 / 39.5 / 42
Weight at follow-up (SD) / -3.3 / -3.26 / -1.25 / -3.69 / -1.27 / -1.46
Length at follow-up (SDS) / -3.81 / -3.02 / -1.0 / -2.4 / -0.77 / -2.13
BMI (SD) / -0.77 / -1.36 / -0.86 / -2.1 / -1.1 / 0.06
HC at follow-up (SDS) / -4.12 / -2.84 / -1.9 / -7.0 / -3.42 / -2.57
Age at sitting in months / 24 / - / 11 / - / - / 12
Sitting at follow-up / unassisted / absent / unassisted / unassisted / absent / unassisted
Age at walking in months / 48 / - / 132 / - / - / 47
Walking at follow-up / assisted / absent / unassisted / absent / absent / assisted
Functional hand use at follow-up / present / present / present / present / absent / present
Speech at follow-up / present / absent / present / absent / absent / present
Age starting expressive speech in months / 42 / - / - / - / - / 24
Number of words spoken / 20 / 0 / 10 / 0 / 0 / 30
Stereotypic movements / present / present / present / present / present / present
Dyskinesia / present / present / absent / present / present / present
Hypotonia / present / present / present / - / present / present
Spasticity / present / absent / present / present / absent / absent
Strabism / present / present / present / - / present / present
Nystagmus / - / - / absent / absent / absent / absent
Abnormal sleep patterns / present / present / present / present / present / present
Social interaction / good / good / good / good / good / good
Eye contact / good / - / good / poor / absent / good
Unexplained episodes of crying / - / - / absent / present / absent / present
Epileptic seizure: Age at onset in months / - / 8 / - / - / 62 / -
Seizures / absent / present / absent / absent / present / absent
Types of seizures / - / complex partial seizures / n.r. / -
Antiepileptic treatment / - / topiramate, clobazam, levetiracetam / no / no / yes / -
Antiepileptic treatment response / - / good / - / - / yes / -
Feeding difficulties / absent / absent / absent / present / present / present
Gastroesophageal reflux / present / present / absent / present / absent / present
Aspiration / present / - / absent / - / present / absent
Constipation / present / present / present / present / absent / present
Hypersalivation / - / - / absent / present / absent / absent
Bruxism / - / - / absent / present / absent / present
Abnormal breathing patterns / - / - / absent / - / absent / absent
Kypho-/scoliosis / - / - / absent / absent / absent / absent
Corpus callosum anomalies / - / absent / absent / absent / present / absent
Cortical anomalies / present / absent / present / present / present / absent

-, missing data

1