De novo KCNMA1 mutations in 3 children with paroxysmal nonkinesigenic dyskinesia and developmental delay
10.3760/cma.j.issn.2095-428X.2017.12.009
- VernacularTitle:KCNMA1基因新生突变致阵发性非运动源性运动障碍伴发育落后3例
- Author:
Maoqiang TIAN
;
Zhongbin ZHANG
;
Kai GAO
;
Tingting BAN
;
Yuwu JIANG
;
Ye WU
- Keywords:
Paroxysmal nonkinesigenic dyskinesia;
Developmental delay;
Epilepsy;
KCNMA1 gene
- From:
Chinese Journal of Applied Clinical Pediatrics
2017;32(12):916-919
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the clinical characteristics of 3 unrelated boys with paroxysmal nonkinesigenic dyskinesia and developmental delay caused by de novo mutation in KCNMA1,and to expand the knowledge of clinical phenotype of KCNMA1 mutation.Methods Clinical data of patients were collected,including gender,age,condition of the perinatal period,personal history,and family history.And the features of genotype data were collected including features of attack,developmental milestones,physical examinations,treatments,and responses to treatment.The data including blood biochemical results,results of metabolic screening and genetic testing and the pedigree validation were collected,while the relationship between phenotype and genotype was analyzed.Results (1)Phenotypic features:3 unrelated boys were diagnosed.The ages of disease onset were 20 days,7 months and 13 months,respectively.All the patients manifested paroxysmal nonkinesigenic dyskinesia and were characterized by the episodes that occurred during wakefulness,presented with sudden onset of asymmetric limb dystonic posture,sometimes with nystagmus and strabismus,or sudden decrease of voluntary movement of limbs with hypotonia and occasional esotropia and yawning.There was no loss of awareness during attack.No precipitating factors were observed before attacks.The developmental milestones were delayed.Three children had no response to anti-epilepsy drug before diagnosis.After diagnosis,2 cases used Clonazepam and 1 case showed less attack.There was not any epileptic seizure until the last follow-up at the ages of 3 years and 6 months old,7 years old,and 5 years and 8 months old,respectively.The frequency of attacks was decreased.The episodes were recorded during video-electroencephalogram(EEG) monitoring,which showed normal ictal and interictal EEG.(2)Genotypic features:all 3 children were detected to have KCNMA1 genetic heterozygous missense mutation,while c.2650G>A (p.Glu884Lys) mutation was identified in 1 patient,and c.3158A>G(p.Asn1053Ser)mutation in the other 2 patients,but no such mutation was found in their parents.Conclusion This finding expands the phenotype of KCNMA1mutation.KCNMA1 should be considered as one of the candidate genes for screening in patients with early onset of paroxysmal nonkinesigenic dyskinesia without triggers,or early-onset of developmental delay,with or without epilepsy.
