Compassionate use of everolimus for refractory epilepsy in a patient with MTOR mosaic mutation.
Eur J Med Genet
; 63(11): 104036, 2020 Nov.
Article
en En
| MEDLINE
| ID: mdl-32805448
ABSTRACT
The MTOR gene encodes the mechanistic target of rapamycin (mTOR), which is a core component of the PI3K-AKT-mTOR signaling pathway. Postzygotic MTOR variants result in various mosaic phenotypes, referred to in OMIM as Smith-Kinsgmore syndrome or focal cortical dysplasia. We report here the case of a patient, with an MTOR mosaic gain-of-function variant (p.Glu2419Lys) in the DNA of 41% skin cells, who received compassionate off-label treatment with everolimus for refractory epilepsy. This 12-year-old-girl presented with psychomotor regression, intractable seizures, hypopigmentation along Blaschko's lines (hypomelanosis of Ito), asymmetric regional body overgrowth, and ocular anomalies, as well as left cerebral hemispheric hypertrophy with some focal underlying migration disorders. In response to the patient's increasingly frequent epileptic seizures, everolimus was initiated (after approval from the hospital ethics committee) at 5 mg/day and progressively increased to 12.5 mg/day. After 5 months of close monitoring (including neuropsychological and electroencephalographic assessment), no decrease in seizure frequency was observed. Though the physiopathological rationale was good, no significant clinical response was noticed under everolimus treatment. A clinical trial would be needed to draw conclusions, but, because the phenotype is extremely rare, it would certainly need to be conducted on an international scale.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Epilepsias Parciales
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Anomalías Craneofaciales
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Inhibidores de Proteínas Quinasas
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Malformaciones del Desarrollo Cortical
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Ensayos de Uso Compasivo
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Serina-Treonina Quinasas TOR
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Everolimus
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Mutación con Ganancia de Función
Límite:
Child
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Female
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Humans
Idioma:
En
Revista:
Eur J Med Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia