Deep histopathology genotype–phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb

Table 1 Individuals included in the study

ID	Age	Onset	Diagnosis	Gene variant/Ref.	VAF	Family history	FU
1	33	0.5	FCD IIa	DEPDC5 (SNV) [47]	Germline	None	IVA (48)
2	20	4.5	FCD IIa	DEPDC5 (SNV) [2]	Germline	None	IIA (24)
3	42	5.5	FCD IIa	DEPDC5 (CNN-LOH) [37]	Somatic (3.7%)	Father’s sister	IIB (24)
4	12	2.8	FCD IIa	DEPDC5 (SNV + LOH) [37]	Two-hit*	None	IIA (48)
5	36	9	FCD IIa	DEPDC5 (SNV) [37]	Germline	Brother son	IA (24)
6	3	0.25	FCD IIa	DEPDC5 (CNN-LOH) [37]	Somatic (4.3%)	None	IA (24)
7	1.5	0.4	FCD IIa	DEPDC5 (SNV)^§	Germline	Sister	IA (24)
8	5	0.7	FCD IIa	NPRL3 (SNV) [37]	Germline	None	IA (24)
9	0.4	0	FCD IIa	NPRL3 (SNV) [37]	Germline	None	IA (16)
10	17	3.5	FCD IIa	NPRL3 (SNV) [47]	Somatic (4.5%)	None	IA (24)
11	0.5	0.1	FCD Iib/HME	MTOR (SNV) [37]	Somatic (10.5%)	None	IA (24)
12	40	17.5	FCD IIa	MTOR (SNV) [37]	Somatic (5%)	None	IA (24)
13	0.8	0.3	FCD IIa/HME	MTOR (SNV) [37]	Somatic (3.4%)	None	IA (24)
14	10	3	FCD IIb	MTOR (SNV) [37]	Somatic (5.3%)	None	IA (24)
15	19	9.5	FCD IIb	MTOR (SNV) [37]	Somatic (3.5%)	None	IA (24)
16	0.9	0.2	FCD IIb	MTOR (SNV) [37]	Somatic (3.1%)	None	IA (24)
17	0.6	0	FCD IIb/PMG	MTOR (SNV) [37]	Somatic (4.3%)	None	IA (24)

Age at surgery in years; Onset: age at seizure onset; sex not shown with 50% males versus 50% females for FCD IIa and FCD IIb, respectively; Lobe: Epileptogenic focus (resulting from EEG, MRI and clinical evaluation)
F frontal, T temporal, P parietal, mult multiple lobes, O occipital; Gene variant results obtained from genetic testing, SNV single nucleotide variant, CNN-LOH copy number neutral loss of heterozygosity, VAF variant allelic frequency, Ref. specific mutation described in cited reference
*Germline variant at VAF = 43.1% and second hit somatic loss of heterozygosity at VAF = 3.7%
^$Variant not previously published and specified below; Diagnosis histopathology diagnosis, HME hemimegalencephaly, PMG polymicrogyria, FU Follow-up 2 years after surgery according to Engel`s classification: IA completely seizure free, IIA initially seizure-free, rare seizures now, IIB rare seizures since surgery, IVA no worthwhile improvement (latest available FU in month after surgery)

ISSN: 2051-5960