. 2021 Sep 25;3(4):fcab222. doi: 10.1093/braincomms/fcab222

Table 3.

A summary of the epidemiological, genetic and phenotypic characteristics of GATOR1-related epilepsies

Clinical characteristics
Prevalence in focal epilepsy cohorts
Focal epilepsy cohort (n = 404), mostly comprised of familial non-lesional cases⁴	9.4%
Focal epilepsy cohort (n = 93), mostly comprised of familial non-lesional cases⁶³	11%
Non-lesional focal epilepsy cohort (n = 112, 66% sporadic)³	8%
Familial non-lesional focal epilepsy cohort (n = 525)¹¹²	2.6%
Sporadic non-lesional focal epilepsy cohort (n = 3400)¹¹³	0.2%
Distribution of GATOR1 variants¹¹
DEPDC5	83%
NPLR2	11%
NPLR3	6%
Mode of inheritance¹¹
De novo	4%
Inherited	96%
Frequency of mutation types¹¹
Loss-of-function	67%
Missense	27%
Splice-region	4%
In-frame deletion	1%
Penetrance¹¹^,¹¹¹	66%
^a Age of seizure onset³^,¹¹^,^61–63^,¹¹¹^,^114–120	mean= 9 years
^a Age of seizure onset³^,¹¹^,^61–63^,¹¹¹^,^114–120	Range= 0–52 years
^b Distribution of epilepsy phenotypes
Nocturnal frontal lobe epilepsy⁴^,¹¹^,³⁶^,¹¹¹^,^115–117^,¹²¹	42%
Temporal lobe epilepsy (including lateral)³^,⁴^,¹¹^,¹¹¹^,¹¹⁸	7%
Familial focal epilepsy with variable foci³^,³⁶^,⁶³^,¹¹¹^,¹¹⁴^,¹¹⁵	11%
^cOther focal epilepsies³^,⁴^,¹¹^,³¹^,³⁶^,^61–63^,¹¹⁴^,¹¹⁵^,¹²⁰	26%
Epileptic spasms¹¹^,¹¹⁹	6%
Generalised epilepsy¹¹^,³¹^,¹²⁷^,¹⁴⁵	4%
Childhood epilepsy with centrotemporal spikes¹²⁰	3%
Complex febrile seizures¹¹	1%
^d Frequency of malformations of cortical development¹¹^,³¹^,³⁶^,^61–63^,¹¹¹^,^114–121^,¹²⁷^,¹⁴⁵	23%
Frequency of drug-resistant epilepsy¹¹	54%
^e Frequency of sudden unexpected death in epilepsy in families with GATOR1 pathogenic variants¹¹^,⁶³^,¹²⁷	9.3%
Frequency of cognitive comorbidities¹¹	46%
Autism spectrum disorders¹¹	9%
Frequency of psychiatric comorbidities¹¹	43%
Oppositional disorder	18%
Attention deficit hyperactivity disorder	15%
Depression or anxiety	8%

The mean age of seizure onset was calculated from a cohort of 268 individuals with GATOR1-related epilepsies reported in the literature.

The distribution of epilepsy phenotypes was estimated from a collection of 152 GATOR1-related epilepsy pedigrees.

Occipital lobe epilepsy, parietal lobe epilepsy or unspecified focal epilepsy.

The frequency of malformations in GATOR1-related epilepsies was estimated from a collection of 143 pedigrees. Reported malformations of cortical development included focal cortical dysplasia type I and II, bottom-of-sulcus dysplasia. hemimegalencephaly, subcortical heterotopia, polymicrogyria and pachygyria.

Fourteen SUDEP cases in 155 DEPDC5 pedigrees; 1 SUDEP case in 10 NPRL2 pedigrees; 2 SUDEP cases in 18 NPRL3 pedigrees.¹¹