Clinical manifestaions and genetics analysis of KCNMA1-related neurological disorders
10.3760/cma.j.cn431274-20231107-00521
- VernacularTitle:KCNMA1基因变异相关神经系统疾病的临床与遗传学分析
- Author:
Langui PAN
1
;
Juan XIONG
;
Guoli WANG
;
Fei YIN
Author Information
1. 江西省儿童医院儿童保健科，南昌 330038
- Keywords:
Mutation;
KCNMA1 gene;
Nervous system diseases
- From:
Journal of Chinese Physician
2023;25(12):1764-1768
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical manifestations and determine the molecular etiology for three KCNMA1-related neurological disorders.Methods:A retrospective clinical data analysis was performed on 3 patients with clinically and genetically diagnosed neurological diseases related to KCNMA1 gene variants who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University from January 2020 to December 2022.Results:Case 1, a 4-year-old and 8-month-old female, was diagnosed with " episodes of head-raising and lowering for 11 months". The electroencephalogram (EEG) showed background theta rhythm in the occipital area, with mainly sharp waves and peaks in the bilateral central, parietal, occipital and temporal areas. Slow waves were scattered or paroxysmal, affecting the central, parietal, and temporal areas on the right side. Levetiracetam was given as an anti-epileptic treatment, and the seizures were completely controlled. Physical examination revealed unclear articulation and short stature. The patient′s mental development has been delayed since childhood. After 2 years of rehabilitation treatment, his motor development was normal and his language development was slightly delayed. Whole-exome sequencing found a novel c. 1807A>G (p.Thr603Ala) mutation in the KCNMA1 gene, which was graded likely pathogenic (LP). Case 2, a male, 1 year and 4 months old, went to the hospital because of " recurrent stupor attacks for more than 6 months". Nearly 20 epileptic events were detected on the electroencephalogram. Levetiracetam, sodium valproate and clonazepam were administered successively. Seizure treatment, complete seizure control. Brain magnetic resonance imaging (MRI) showed poor cerebellar development. Development was lagging behind that of normal children of the same age. Whole-exome sequencing found a novel c. 756C>A (p.Phe252Leu) mutation in the KCNMA1 gene, which was graded LP. Case 3, a 16-month-old female, went to the hospital because of " trembling upper limbs, slurred speech for more than 10 years, and unsteady gait for 8 years." The electroencephalogram showed no abnormalities, and brain MRI showed cerebellar atrophy. Physical examination: unclear speech, unsteady grasping of objects with both hands, muscle strength of limbs level 4, and ataxic gait. Whole-exome sequencing found a novel c. 1051T>C (p.Ser351Pro) mutation in the KCNMA1 gene, which was graded LP.Conclusions:The core phenotypes of KCNMA1 gene mutation-related neurological diseases include epilepsy, neurodevelopmental disorders and paroxysmal dyskinesia, and cerebellar atrophy is common in brain MRI.
