Clinical spectrum and treatment responses in.

OBJECTIVE

To compare the genotype-phenotype relationships betweenchildren with PRRT2 gene variants and 16p11.2 microdeletion syndrome.

METHODS

A retrospective analysis was performed on clinical data from 68 patients with PRRT2 variants and 16 patients with 16p11.2 microdeletionsyndrome at the Children’s Hospital of Chongqing Medical Universitybetween February 2015 and August 2024. Genetic testing included whole-exome sequencing and copy number variation sequencing.

RESULTS

(1) PRRT2 Cohort (n=68): Clinical diagnoses included benign familial infantile epilepsy (49/68), paroxysmal kinesigenic dyskinesia (4/68),infantile convulsions with paroxysmal choreoathetosis (8/68), and otherepilepsy subtypes (7/68). Genetic analysis revealed frameshift variants in 89.7% (61/68), with c.649dupC as the predominant mutation(penetrance:77.2%). Electroencephalography detected epileptiformdischarges in 45.6% of cases. Brain MRI showed nonspecific abnormalities,including widened extra-axial spaces (75%). Oxcarbazepine showed bettertherapeutic efficacy than levetiracetam. (2) 16p11.2 microdeletion cohort (n=16): This group exhibited moresevere phenotypes: The incidence of persistent status epilepticus may behigher (18.8% vs 2.9%, P=0.045, q=0.084), with 87.5% being de novovariants and 81.2% having negative family history. Compared with the PRRT2 group, these patients had significantly increased risks of congenitalheart disease, global developmental delay, and structural brainabnormalities (all P < 0.05).

CONCLUSION

PRRT2-related disorders are characterized by incompletepenetrance and benign clinical courses, whereas 16p11.2 microdeletionsyndrome manifests complex phenotypic spectra due to polygenicinvolvement, necessitating distinct diagnostic and therapeutic strategies.