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

Box 1.

‘Brain only’ versus multisystem mTORopathies

‘Brain only’ mTORopathies

GATOR1-related focal epilepsies (germline DEPDC5, NPLR2 and NPRL3)
Focal cortical dysplasia type II (somatic MTOR, AKT3, PIK3CA and RHEB)
Hemimegalencephaly (somatic MTOR, AKT3, PIK3CA, RHEB and PTEN)
Infantile-onset developmental and epileptic encephalopathies (germline SZT2 and KPTN)^a

Multisystem mTORopathies

Tuberous sclerosis complex (germline and somatic TSC1 and TSC2)
Smith–Kingsmore syndrome (germline and somatic MTOR)^a
- Dysmorphic facial features, intellectual disability, herniae, hypomelanosis, small thorax
Polyhydramnios, megalencephaly, and symptomatic epilepsy (germline STRADA)^a
- Polyhydramnios, facial dysmorphism, intellectual disability, skeletal deformity, cardiac anomalies
Megalencephaly capillary malformation syndrome (germline and somatic PIK3CA)^a
- Cutaneous vascular malformations, intellectual disability, digital abnormalities, cardiac anomalies
Megalencephaly Polymicrogyria-Polydactyly Hydrocephalus (germline AKT3 and PIK3R2)^a
- Intellectual disability, postaxial polydactyly, facial dysmorphism
Proteus syndrome (somatic AKT1)^a
- Patchy or segmental overgrowth and hyperplasia of multiple tissues
Bannayan–Riley–Ruvalcaba syndrome (germline PTEN)^a
- Childhood onset, macrocephaly, lipomas, hamartomas, intellectual disability
Cowden syndrome (germline PTEN)^a
- Adult onset, multiple hamartomas, increased cancer risk, Lhermitte-Duclos disease, macrocephaly
CLOVES syndrome (somatic PIK3CA)^a
- Lipomatous overgrowth, lymphatic malformations, vascular malformations, skeletal anomalies
TBC1D7-related macrocephaly (germline TBC1D7)^a
- Patellar dislocation, osteoarticular anomalies, coeliac disease, intellectual disability

Very rare mTORopathies.