[MIM 614 498]

(Lethal neonatal syndrome of spasticity-epileptic encephalopathy, RMFSL, acronym in English for Rigidity and MultiFocal Seizure syndrome, Lethal, neonatal)

Prevalence< 1.106. Autosomal recessive transmission of a mutation of the BRAT1 gene (7p22.3), coding for the protein 'BRCA1 associated ATM activator 1' involved in DNA repair, apoptosis and mitochondrial homeostasis. It causes very severe neonatal encephalopathy resulting in the death of most infants within a few months after birth.

Clinical presentation:

• muscle twitching in utero, sometimes arthrogryposis
• generalized hypertonia with multifocal myoclonus, spontaneous or in response to stimulation, of non-epileptic origin, often confused with hyperexplexia (see this term)
• onset around 2 weeks of life of refractory multifocal epileptic seizures associated with apnea episodes with bradycardia
• acquired microcephaly, lack of response to visual stimulation, feeding difficulties

A biallelic form (compound heterozygosis) of mutations of the BRAT1 gene results in the NEDCAS syndrome  (see this term)

Anesthetic implications: 

refractory epilepsy

References : 

-        Fowkes R, Elwan M, Akay E, Mitchell CJ, Thomas RH, Lewis-Smith D.
A review of the clinical spectrum of BRAT1 disorders and case of developmental and epileptic encephalopathy surviving into adulthood.
Epilepsy & Behavior Reports, 2022 ; 19 :100549.

-        Carapancea E, Cornet M-C, Milh M, De Cosmo L, Huang EJ, Granata T, Striano P,  Ceulemans B et al.
Clinical and neurophysiological phenotypes in neonates with BRAT1 encephalopathy.
Neurology 2023 ; DOI: https://doi.org/10.1212/WNL.0000000000206755

Updated: March 2023