Epilepsy in Nicolaides–Baraitser Syndrome: Review of Literature and Report of 25 Patients Focusing on Treatment Aspects

Abstract

Nicolaides–Baraitser syndrome (NCBRS), caused by a mutation in the SMARCA2 gene, which goes along with intellectual disability, congenital malformations, especially of face and limbs, and often difficult-to-treat epilepsy, is surveyed focusing on epilepsy and its treatment. Patients were recruited via “Network Therapy of Rare Epilepsies (NETRE)” and an international NCBRS parent support group. Inclusion criterion is NCBRS-defining SMARCA2 mutation. Clinical findings including epilepsy classification, anticonvulsive treatment, electroencephalogram (EEG) findings, and neurodevelopmental outcome were collected with an electronic questionnaire. Inclusion of 25 NCBRS patients with epilepsy in 23 of 25. Overall, 85% of the participants (17/20) reported generalized seizures, the semiology varied widely. EEG showed generalized epileptogenic abnormalities in 53% (9/17), cranial magnetic resonance imaging (cMRI) was mainly inconspicuous. The five most frequently used anticonvulsive drugs were valproic acid (VPA [12/20]), levetiracetam (LEV [12/20]), phenobarbital (PB [8/20]), topiramate (TPM [5/20]), and carbamazepine (CBZ [5/20]). LEV (9/12), PB (6/8), TPM (4/5), and VPA (9/12) reduced the seizures' frequency in more than 50%. Temporary freedom of seizures (>6 months) was reached with LEV (4/12), PB (3/8), TPM (1/5, only combined with PB and nitrazepam [NZP]), and VPA (4/12). Seizures aggravation was observed under lamotrigine (LTG [2/4]), LEV (1/12), PB (1/8), and VPA (1/12). Ketogenic diet (KD) and vagal nerve stimulation (VNS) reduced seizures' frequency in one of two each. This first worldwide retrospective analysis of anticonvulsive therapy in NCBRS helps to treat epilepsy in NCBRS that mostly shows only initial response to anticonvulsive therapy, especially with LEV and VPA, but very rarely shows complete freedom of seizures in this, rather genetic than structural epilepsy.

Caudal regression in fetus with de novo SMARCA2 pathogenic variant

“…1 Furthermore, there is currently no consensus of the clinical diagnostic criteria for NCBRS; most of the known clinical features present in infancy or childhood with no prenatal or ultrasound criteria currently included. 1,2,4,5 Our findings may be incidental findings related to a secondary cause or may represent a severe form of this condition. If any further cases are described with this combination of phenotype and pathogenic variant, sacral agenesis and congenital vertical talus should be added to the spectrum of diagnostic traits for NCBRS.…”

“…To our knowledge, this phenotypic pairing has never been described in the literature. 1,2,4,5 Prenatal ultrasound findings of NCBRS have not been well described in the literature; few prior published reports describe a possible association with mild fetal growth restriction. 1 Furthermore, there is currently no consensus of the clinical diagnostic criteria for NCBRS; most of the known clinical features present in infancy or childhood with no prenatal or ultrasound criteria currently included.…”

Epilepsy and Cognitive Impairment in Childhood and Adolescence: A Mini-Review

“…Nicolaides-Baraitser syndrome is caused by a mutation in the SMARCA2 gene that goes along with intellectual disability, congenital malformations of the face and limbs and often difficult-to-treat epilepsy [ 33 ].…”