Overview
RERE-related neurodevelopmental syndrome encompasses a spectrum of genetic disorders characterized by neurodevelopmental impairments, often including intellectual disability, facial dysmorphisms, and variable neurological features such as epilepsy. Specific genetic mutations include those in CSNK2B, NCAPG2, PPP1R21, and EBF3, each contributing distinct clinical presentations 1234.Diagnosis
Genetic Testing: Whole-exome or whole-genome sequencing to identify pathogenic variants in CSNK2B, NCAPG2, PPP1R21, or EBF3 1234.
Clinical Features: Presence of intellectual disability, facial dysmorphisms, epilepsy (often with early onset), and additional features like ocular abnormalities, urogenital defects, or cerebellar ataxia 124.
Neurodevelopmental Assessment: Cognitive testing and developmental milestones evaluation 14.
Electroclinical Evaluation: EEG to assess seizure types and patterns 1.Management
Anti-Seizure Medications: Initiate with first-line drugs such as valproate, levetiracetam, or lamotrigine; adjust based on seizure type and response 1.
Supportive Therapies: Early intervention programs for developmental delays, physical therapy, and occupational therapy 14.
Behavioral Support: Psychological and behavioral interventions tailored to individual needs 14.
Multidisciplinary Care: Collaboration among neurologists, geneticists, developmental pediatricians, and allied health professionals 14.Special Populations
Pediatrics: Early identification and intervention crucial for optimizing developmental outcomes 14.
Comorbidities: Monitor and manage associated conditions like vesicoureteric reflux or renal anomalies 24.Key Recommendations
Genetic Testing for Suspected Cases: Implement whole-exome or whole-genome sequencing in patients with unexplained neurodevelopmental disorders and characteristic features 1234 (Evidence: Strong).
Early Initiation of Anti-Seizure Therapy: Start with appropriate anti-epileptic drugs early in the course of epilepsy to manage seizure types effectively 1 (Evidence: Moderate).
Comprehensive Developmental Support: Provide multidisciplinary support including early intervention programs and behavioral therapies to address cognitive and motor delays 14 (Evidence: Moderate).References
1 Trivisano M, Dominicis A, Stregapede F, Quintavalle C, Micalizzi A, Cappelletti S et al.. Refining of the electroclinical phenotype in familial and sporadic cases of CSNK2B-related Neurodevelopmental Syndrome. Epilepsy & behavior : E&B 2023. link
2 Khan TN, Khan K, Sadeghpour A, Reynolds H, Perilla Y, McDonald MT et al.. Mutations in NCAPG2 Cause a Severe Neurodevelopmental Syndrome that Expands the Phenotypic Spectrum of Condensinopathies. American journal of human genetics 2019. link
3 Rehman AU, Najafi M, Kambouris M, Al-Gazali L, Makrythanasis P, Rad A et al.. Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function. Human mutation 2019. link
4 Sleven H, Welsh SJ, Yu J, Churchill MEA, Wright CF, Henderson A et al.. De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome. American journal of human genetics 2017. link